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Durable transfusion independence in MDS with imetelstat
AMSTERDAM – For patients with low-risk myelodysplastic syndrome (MDS) for whom erythropoietin therapy has failed, the novel telomerase inhibitor imetelstat may provide long-lasting independence from transfusion, investigators reported.
Among 38 patients with low-risk MDS who had relapsed or were refractory to treatment with an erythropoiesis stimulating agent (ESA) who received imetelstat, 16 (42%) were free from the need for transfusion for at least 8 weeks, with one patient being transfusion free for up to 141 weeks, reported Pierre Fenaux, MD, of Hôpital Saint-Louis in Paris.
Patients with a generally worse prognosis “tended to respond better to imetelstat in terms of transfusion independence, which suggests that the drug is promising for higher-risk MDS,” he said at a briefing prior to his presentation of the data at the annual congress of the European Hematology Association.
Imetelstat is a first-in-class telomerase inhibitor targeting cells with short telomere lengths and active telomerase, the enzyme that maintains telomere length. Higher telomerase activity and shorter telomeres are predictive of shorter overall survival in patients with MDS, Dr. Fenaux explained.
He and colleagues enrolled 38 patients, median age 71.5 years, with low-risk MDS, with an International Prognostic Scoring System (IPSS) score of low or intermediate-1, whose disease was relapsed or refractory to ESA or to erythropoietin at a dose of more than 500 mU/mL. Of this group, 24 patients had IPSS low disease, 14 had intermediate-1 disease.
The median transfusion burden was 8 units per 8 weeks (range 4-14). The majority of patients (34, or 89%) had received prior ESAs.
The patients were transfusion dependent, defined as the need for 4 or more units of red blood cells within 8 weeks over the 16 weeks prior to study entry.
No patients had the 5q deletion, and no patients had received either a hypomethylating agent or lenolidamide (Revlimid), neither of which are approved for this indication in Europe.
The patients received imetelstat 7.5 mg/kg intravenously every 4 weeks.
As noted earlier, 16 patients (42%) achieved the primary endpoint of 8-week transfusion independence, with a median duration of 85.9 weeks (range 8-141 weeks).
Eleven patients (29%) had transfusion independence lasting at least 24 weeks – a secondary endpoint – and 26 (68%) met International Working Group 2006 criteria for a HI-E (erythroid) response, with 12 of these patients having an increase in hemoglobin of 1.5 g/dL or greater lasting for at least 8 weeks, and all 26 having a reduction in transfusions of 4 or more units over 8 weeks.
There was evidence to suggest a disease-modifying effect of imetelstat, with five patients achieving a complete response (CR), and five having a marrow CR.
The most frequent adverse events were manageable and reversible grade 3 or greater cytopenias, but there were no new safety signals seen. Two patients were hospitalized for febrile neutropenia, but there were no treatment-related deaths.
Based on these results, investigators are planning a phase 3 study comparing imetelstat with placebo in a 2:1 ratio. The trial is scheduled to begin in the late summer or fall of 2019.
When asked if imetelstat might have off-target effects by inhibiting telomerase in other cells, Dr. Fenaux replied that the mechanism of action is unclear, and that its potential effects on erythropoiesis are still unknown.
Briefing moderator Anton Hagenbeek, MD, of Amsterdam University Medical Center, commented on the drug’s potential for treating MDS, and asked whether investigators are considering combining it with other therapies for MDS.
“I think the first step will be to study it in high-risk MDS as a single agent before combining it, including with hypomethylating agents, et cetera,” Dr. Fenaux replied.
SOURCE: Fenaux P et al. EHA 2019, Abstract S837.
AMSTERDAM – For patients with low-risk myelodysplastic syndrome (MDS) for whom erythropoietin therapy has failed, the novel telomerase inhibitor imetelstat may provide long-lasting independence from transfusion, investigators reported.
Among 38 patients with low-risk MDS who had relapsed or were refractory to treatment with an erythropoiesis stimulating agent (ESA) who received imetelstat, 16 (42%) were free from the need for transfusion for at least 8 weeks, with one patient being transfusion free for up to 141 weeks, reported Pierre Fenaux, MD, of Hôpital Saint-Louis in Paris.
Patients with a generally worse prognosis “tended to respond better to imetelstat in terms of transfusion independence, which suggests that the drug is promising for higher-risk MDS,” he said at a briefing prior to his presentation of the data at the annual congress of the European Hematology Association.
Imetelstat is a first-in-class telomerase inhibitor targeting cells with short telomere lengths and active telomerase, the enzyme that maintains telomere length. Higher telomerase activity and shorter telomeres are predictive of shorter overall survival in patients with MDS, Dr. Fenaux explained.
He and colleagues enrolled 38 patients, median age 71.5 years, with low-risk MDS, with an International Prognostic Scoring System (IPSS) score of low or intermediate-1, whose disease was relapsed or refractory to ESA or to erythropoietin at a dose of more than 500 mU/mL. Of this group, 24 patients had IPSS low disease, 14 had intermediate-1 disease.
The median transfusion burden was 8 units per 8 weeks (range 4-14). The majority of patients (34, or 89%) had received prior ESAs.
The patients were transfusion dependent, defined as the need for 4 or more units of red blood cells within 8 weeks over the 16 weeks prior to study entry.
No patients had the 5q deletion, and no patients had received either a hypomethylating agent or lenolidamide (Revlimid), neither of which are approved for this indication in Europe.
The patients received imetelstat 7.5 mg/kg intravenously every 4 weeks.
As noted earlier, 16 patients (42%) achieved the primary endpoint of 8-week transfusion independence, with a median duration of 85.9 weeks (range 8-141 weeks).
Eleven patients (29%) had transfusion independence lasting at least 24 weeks – a secondary endpoint – and 26 (68%) met International Working Group 2006 criteria for a HI-E (erythroid) response, with 12 of these patients having an increase in hemoglobin of 1.5 g/dL or greater lasting for at least 8 weeks, and all 26 having a reduction in transfusions of 4 or more units over 8 weeks.
There was evidence to suggest a disease-modifying effect of imetelstat, with five patients achieving a complete response (CR), and five having a marrow CR.
The most frequent adverse events were manageable and reversible grade 3 or greater cytopenias, but there were no new safety signals seen. Two patients were hospitalized for febrile neutropenia, but there were no treatment-related deaths.
Based on these results, investigators are planning a phase 3 study comparing imetelstat with placebo in a 2:1 ratio. The trial is scheduled to begin in the late summer or fall of 2019.
When asked if imetelstat might have off-target effects by inhibiting telomerase in other cells, Dr. Fenaux replied that the mechanism of action is unclear, and that its potential effects on erythropoiesis are still unknown.
Briefing moderator Anton Hagenbeek, MD, of Amsterdam University Medical Center, commented on the drug’s potential for treating MDS, and asked whether investigators are considering combining it with other therapies for MDS.
“I think the first step will be to study it in high-risk MDS as a single agent before combining it, including with hypomethylating agents, et cetera,” Dr. Fenaux replied.
SOURCE: Fenaux P et al. EHA 2019, Abstract S837.
AMSTERDAM – For patients with low-risk myelodysplastic syndrome (MDS) for whom erythropoietin therapy has failed, the novel telomerase inhibitor imetelstat may provide long-lasting independence from transfusion, investigators reported.
Among 38 patients with low-risk MDS who had relapsed or were refractory to treatment with an erythropoiesis stimulating agent (ESA) who received imetelstat, 16 (42%) were free from the need for transfusion for at least 8 weeks, with one patient being transfusion free for up to 141 weeks, reported Pierre Fenaux, MD, of Hôpital Saint-Louis in Paris.
Patients with a generally worse prognosis “tended to respond better to imetelstat in terms of transfusion independence, which suggests that the drug is promising for higher-risk MDS,” he said at a briefing prior to his presentation of the data at the annual congress of the European Hematology Association.
Imetelstat is a first-in-class telomerase inhibitor targeting cells with short telomere lengths and active telomerase, the enzyme that maintains telomere length. Higher telomerase activity and shorter telomeres are predictive of shorter overall survival in patients with MDS, Dr. Fenaux explained.
He and colleagues enrolled 38 patients, median age 71.5 years, with low-risk MDS, with an International Prognostic Scoring System (IPSS) score of low or intermediate-1, whose disease was relapsed or refractory to ESA or to erythropoietin at a dose of more than 500 mU/mL. Of this group, 24 patients had IPSS low disease, 14 had intermediate-1 disease.
The median transfusion burden was 8 units per 8 weeks (range 4-14). The majority of patients (34, or 89%) had received prior ESAs.
The patients were transfusion dependent, defined as the need for 4 or more units of red blood cells within 8 weeks over the 16 weeks prior to study entry.
No patients had the 5q deletion, and no patients had received either a hypomethylating agent or lenolidamide (Revlimid), neither of which are approved for this indication in Europe.
The patients received imetelstat 7.5 mg/kg intravenously every 4 weeks.
As noted earlier, 16 patients (42%) achieved the primary endpoint of 8-week transfusion independence, with a median duration of 85.9 weeks (range 8-141 weeks).
Eleven patients (29%) had transfusion independence lasting at least 24 weeks – a secondary endpoint – and 26 (68%) met International Working Group 2006 criteria for a HI-E (erythroid) response, with 12 of these patients having an increase in hemoglobin of 1.5 g/dL or greater lasting for at least 8 weeks, and all 26 having a reduction in transfusions of 4 or more units over 8 weeks.
There was evidence to suggest a disease-modifying effect of imetelstat, with five patients achieving a complete response (CR), and five having a marrow CR.
The most frequent adverse events were manageable and reversible grade 3 or greater cytopenias, but there were no new safety signals seen. Two patients were hospitalized for febrile neutropenia, but there were no treatment-related deaths.
Based on these results, investigators are planning a phase 3 study comparing imetelstat with placebo in a 2:1 ratio. The trial is scheduled to begin in the late summer or fall of 2019.
When asked if imetelstat might have off-target effects by inhibiting telomerase in other cells, Dr. Fenaux replied that the mechanism of action is unclear, and that its potential effects on erythropoiesis are still unknown.
Briefing moderator Anton Hagenbeek, MD, of Amsterdam University Medical Center, commented on the drug’s potential for treating MDS, and asked whether investigators are considering combining it with other therapies for MDS.
“I think the first step will be to study it in high-risk MDS as a single agent before combining it, including with hypomethylating agents, et cetera,” Dr. Fenaux replied.
SOURCE: Fenaux P et al. EHA 2019, Abstract S837.
REPORTING FROM EHA CONGRESS
Past donor pregnancy, sex do not affect transfusion-related mortality
Red blood cell (RBC) transfusions from either previously pregnant, sex-discordant, or female donors were not significantly associated with higher mortality among transfusion recipients, according to a retrospective analysis of more than 1 million donors.
“This study used data from 3 large cohorts in the United States and Scandinavia to investigate whether blood donor sex and pregnancy history were associated with mortality of transfusion recipients,” wrote Gustaf Edgren, MD, PhD, of Karolinska University Hospital, Stockholm, and colleagues. The findings were published in JAMA.
The researchers analyzed data from three separate cohorts that included a combined 1,047,382 red blood cell transfusion recipients. Data collected included donor-related information, such as sex and pregnancy history, as well as survival data of transfusion recipients. The primary outcome measured was in-hospital mortality, and the secondary outcome was long-term mortality. Data were collected until Dec. 31, 2016.
The researchers found no statistically significant associations between either sex-discordant donors (male donor to female recipient or female donor to male recipient), female donors, or previously pregnant donors and in-hospital mortality of transfusion recipients.
The hazard ratio estimates for each unit transfused from a previously pregnant donor ranged from 1.00-1.01 in the three cohorts. Similarly, the HR estimates ranged from 0.99-1.00 for female donors in the three cohorts and 0.99-1.02 for sex discordant donors.
The only significant association found was observed in the smallest cohort of 34,662 recipients. Researchers found an increased risk of death in patients who received one to two sex discordant transfusions (HR, 1.08; 95% confidence interval, 1.03-1.14) or five to six transfusions (HR, 1.14; 95%CI, 1.01-1.29), compared with recipients who received no sex-discordant transfusions.
“The results are reassuring in that the survival of patients who got transfused with red blood cells does not appear to be associated with whether the blood they received was donated by a man, by a woman who had been pregnant — or by one who had not. That’s important to know,” Simone Glynn, MD, chief of the Blood Epidemiology and Clinical Therapeutics Branch at the National Heart, Lung, and Blood Institute, as well as a study author, said in a statement.
The study was funded by the National Heart, Lung, and Blood Institute. The authors reported financial disclosures related to the National Institutes of Health, RTI International, Cerus, AABB, Creative Testing Solutions, and the Nordic Cancer Union.
SOURCE: Edgren G et al. JAMA. 2019 Jun 11. doi: 10.1001/jama.2019.7084.
Red blood cell (RBC) transfusions from either previously pregnant, sex-discordant, or female donors were not significantly associated with higher mortality among transfusion recipients, according to a retrospective analysis of more than 1 million donors.
“This study used data from 3 large cohorts in the United States and Scandinavia to investigate whether blood donor sex and pregnancy history were associated with mortality of transfusion recipients,” wrote Gustaf Edgren, MD, PhD, of Karolinska University Hospital, Stockholm, and colleagues. The findings were published in JAMA.
The researchers analyzed data from three separate cohorts that included a combined 1,047,382 red blood cell transfusion recipients. Data collected included donor-related information, such as sex and pregnancy history, as well as survival data of transfusion recipients. The primary outcome measured was in-hospital mortality, and the secondary outcome was long-term mortality. Data were collected until Dec. 31, 2016.
The researchers found no statistically significant associations between either sex-discordant donors (male donor to female recipient or female donor to male recipient), female donors, or previously pregnant donors and in-hospital mortality of transfusion recipients.
The hazard ratio estimates for each unit transfused from a previously pregnant donor ranged from 1.00-1.01 in the three cohorts. Similarly, the HR estimates ranged from 0.99-1.00 for female donors in the three cohorts and 0.99-1.02 for sex discordant donors.
The only significant association found was observed in the smallest cohort of 34,662 recipients. Researchers found an increased risk of death in patients who received one to two sex discordant transfusions (HR, 1.08; 95% confidence interval, 1.03-1.14) or five to six transfusions (HR, 1.14; 95%CI, 1.01-1.29), compared with recipients who received no sex-discordant transfusions.
“The results are reassuring in that the survival of patients who got transfused with red blood cells does not appear to be associated with whether the blood they received was donated by a man, by a woman who had been pregnant — or by one who had not. That’s important to know,” Simone Glynn, MD, chief of the Blood Epidemiology and Clinical Therapeutics Branch at the National Heart, Lung, and Blood Institute, as well as a study author, said in a statement.
The study was funded by the National Heart, Lung, and Blood Institute. The authors reported financial disclosures related to the National Institutes of Health, RTI International, Cerus, AABB, Creative Testing Solutions, and the Nordic Cancer Union.
SOURCE: Edgren G et al. JAMA. 2019 Jun 11. doi: 10.1001/jama.2019.7084.
Red blood cell (RBC) transfusions from either previously pregnant, sex-discordant, or female donors were not significantly associated with higher mortality among transfusion recipients, according to a retrospective analysis of more than 1 million donors.
“This study used data from 3 large cohorts in the United States and Scandinavia to investigate whether blood donor sex and pregnancy history were associated with mortality of transfusion recipients,” wrote Gustaf Edgren, MD, PhD, of Karolinska University Hospital, Stockholm, and colleagues. The findings were published in JAMA.
The researchers analyzed data from three separate cohorts that included a combined 1,047,382 red blood cell transfusion recipients. Data collected included donor-related information, such as sex and pregnancy history, as well as survival data of transfusion recipients. The primary outcome measured was in-hospital mortality, and the secondary outcome was long-term mortality. Data were collected until Dec. 31, 2016.
The researchers found no statistically significant associations between either sex-discordant donors (male donor to female recipient or female donor to male recipient), female donors, or previously pregnant donors and in-hospital mortality of transfusion recipients.
The hazard ratio estimates for each unit transfused from a previously pregnant donor ranged from 1.00-1.01 in the three cohorts. Similarly, the HR estimates ranged from 0.99-1.00 for female donors in the three cohorts and 0.99-1.02 for sex discordant donors.
The only significant association found was observed in the smallest cohort of 34,662 recipients. Researchers found an increased risk of death in patients who received one to two sex discordant transfusions (HR, 1.08; 95% confidence interval, 1.03-1.14) or five to six transfusions (HR, 1.14; 95%CI, 1.01-1.29), compared with recipients who received no sex-discordant transfusions.
“The results are reassuring in that the survival of patients who got transfused with red blood cells does not appear to be associated with whether the blood they received was donated by a man, by a woman who had been pregnant — or by one who had not. That’s important to know,” Simone Glynn, MD, chief of the Blood Epidemiology and Clinical Therapeutics Branch at the National Heart, Lung, and Blood Institute, as well as a study author, said in a statement.
The study was funded by the National Heart, Lung, and Blood Institute. The authors reported financial disclosures related to the National Institutes of Health, RTI International, Cerus, AABB, Creative Testing Solutions, and the Nordic Cancer Union.
SOURCE: Edgren G et al. JAMA. 2019 Jun 11. doi: 10.1001/jama.2019.7084.
FROM JAMA
C3 inhibitor shows potential in PNH and AIHA
GLASGOW – APL-2, a complement factor 3 (C3) inhibitor, may be a future treatment option for paroxysmal nocturnal hemoglobinuria (PNH) and autoimmune hemolytic anemia (AIHA), according to investigators from two separate studies.
Early results from the phase 1b PADDOCK trial for PNH and the phase 2 PLAUDIT trial for AIHA showed that APL-2 significantly increased hemoglobin levels, with additional improvements reported in lactate dehydrogenase (LDH), absolute reticulocyte count, and bilirubin. The findings were presented at the annual meeting of the British Society for Haematology.
By blocking C3, APL-2 acts further upstream than approved C5 inhibitors eculizumab and ravulizumab, thereby controlling extravascular hemolysis in addition to intravascular hemolysis. This broader level of control is needed for some patients, the investigators said, such as those with PNH who have inadequate responses to C5 inhibition.
PNH
“Even in PNH patients treated with eculizumab, up to 70% may have suboptimal hemoglobin responses and about 30% may still require blood transfusions,” said lead author of the PADDOCK trial, Raymond Wong, MD, of the Prince of Wales Hospital in Hong Kong.
PNH patients included in the open-label, dose-escalation PADDOCK study had greater than 10% white blood cell clones, LDH that was at least twice the upper limit of normal, at least one transfusion within the past year, a platelet count below 30,000/mm3, and an absolute neutrophil count greater than 500 x 109/L.
Dr. Wong described experiences with a cohort of 20 patients who received 270 mg APL-2 subcutaneously daily for at least 28 days, with the option to continue treatment for up to 2 years thereafter, if desired.
From these 20 patients, 2 patients completed the initial 28-day period but did not elect to continue and 2 patients withdrew because of adverse events (ovarian cancer and severe aplastic anemia), leaving 16 patients in the present analysis. Before treatment, these individuals were transfusion dependent, with an average transfusion rate of 8.7 transfusions per year.
Results showed that mean hemoglobin increased from 8.0 g/dL at baseline to 10.8 g/dL at day 29 and 12.2 g/dL at day 85. LDH dropped 900%, from 2,416 U/L (9 times the upper limit of normal) to 271 U/L (0.9 times the upper limit of normal). Absolute reticulocyte count and bilirubin also normalized.
Overall, these improvements led to a meaningful clinical impact, Dr. Wong said, with fatigue scores improving and most patients becoming transfusion independent on maintenance therapy, with the exception of one patient who developed severe aplastic anemia after 1 year. No significant infections or thromboses occurred.
When asked where APL-2 might fit in with current treatment paradigm, Dr. Wong said that multiple applications for PNH are being investigated, including first-line therapy and after failure of eculizumab.
AIHA
Results from the phase 2 PLAUDIT trial, presented by Bruno Fattizzo, MD, of the University of Milan, offered a glimpse at APL-2 in a different setting: AIHA.
Eligibility required hemoglobin levels of less than 11 g/dL, signs of hemolysis, and positive direct antiglobulin test for IgG and/or complement C3.
Dr. Fattizzo discussed results from five patients with cold agglutinin disease and five patients with C3-positive warm AIHA who had received 56 days of therapy.
Among the five patients with cold agglutinin disease, mean hemoglobin increased from 8.7 g/dL to 12.1 g/dL, while patients with warm C3-positive AIHA had a mean increase from 9.3 g/dL to 11.3 g/dL. As with the PNH study, absolute reticulocyte count, LDH, and indirect bilirubin normalized across all 10 patients.
“Some of the patients included in the trial have already reached more than 48 weeks, something like 64 weeks in the study, and they are still doing well,” Dr. Fattizzo said. “So it really seems that those who are do respond really keep the response with ongoing treatment.”
Nine out of 12 patients with cold agglutinin disease (75%) and 8 out of 9 patients (89%) with warm AIHA experienced adverse events, although these were mostly grade 1 or 2 and deemed unrelated to APL-2 by the investigators.
Five grade 3 adverse events in six patients included oral squamous carcinoma, hemolytic flare, pneumonia, purpura, and acute kidney injury. Five grade 4 adverse events in two patients included high calcium, high creatinine, hypoxia, and hemolytic flare, causing these two patients to withdraw from the study. No grade 3 or 4 adverse events were considered related to APL-2.
“APL-2 appears to be well tolerated and safe,” Dr. Fattizzo said, adding that a phase 3 trial for cold agglutinin disease and C3-positive warm AIHA C3+ is planned.
Both studies are sponsored by Apellis Pharmaceuticals. Dr. Wong and his colleagues reported financial relationships with Alexion Pharmaceuticals, Apellis, Celgene, Janssen, and other companies. Dr. Fattizzo reported having no conflicts of interest.
GLASGOW – APL-2, a complement factor 3 (C3) inhibitor, may be a future treatment option for paroxysmal nocturnal hemoglobinuria (PNH) and autoimmune hemolytic anemia (AIHA), according to investigators from two separate studies.
Early results from the phase 1b PADDOCK trial for PNH and the phase 2 PLAUDIT trial for AIHA showed that APL-2 significantly increased hemoglobin levels, with additional improvements reported in lactate dehydrogenase (LDH), absolute reticulocyte count, and bilirubin. The findings were presented at the annual meeting of the British Society for Haematology.
By blocking C3, APL-2 acts further upstream than approved C5 inhibitors eculizumab and ravulizumab, thereby controlling extravascular hemolysis in addition to intravascular hemolysis. This broader level of control is needed for some patients, the investigators said, such as those with PNH who have inadequate responses to C5 inhibition.
PNH
“Even in PNH patients treated with eculizumab, up to 70% may have suboptimal hemoglobin responses and about 30% may still require blood transfusions,” said lead author of the PADDOCK trial, Raymond Wong, MD, of the Prince of Wales Hospital in Hong Kong.
PNH patients included in the open-label, dose-escalation PADDOCK study had greater than 10% white blood cell clones, LDH that was at least twice the upper limit of normal, at least one transfusion within the past year, a platelet count below 30,000/mm3, and an absolute neutrophil count greater than 500 x 109/L.
Dr. Wong described experiences with a cohort of 20 patients who received 270 mg APL-2 subcutaneously daily for at least 28 days, with the option to continue treatment for up to 2 years thereafter, if desired.
From these 20 patients, 2 patients completed the initial 28-day period but did not elect to continue and 2 patients withdrew because of adverse events (ovarian cancer and severe aplastic anemia), leaving 16 patients in the present analysis. Before treatment, these individuals were transfusion dependent, with an average transfusion rate of 8.7 transfusions per year.
Results showed that mean hemoglobin increased from 8.0 g/dL at baseline to 10.8 g/dL at day 29 and 12.2 g/dL at day 85. LDH dropped 900%, from 2,416 U/L (9 times the upper limit of normal) to 271 U/L (0.9 times the upper limit of normal). Absolute reticulocyte count and bilirubin also normalized.
Overall, these improvements led to a meaningful clinical impact, Dr. Wong said, with fatigue scores improving and most patients becoming transfusion independent on maintenance therapy, with the exception of one patient who developed severe aplastic anemia after 1 year. No significant infections or thromboses occurred.
When asked where APL-2 might fit in with current treatment paradigm, Dr. Wong said that multiple applications for PNH are being investigated, including first-line therapy and after failure of eculizumab.
AIHA
Results from the phase 2 PLAUDIT trial, presented by Bruno Fattizzo, MD, of the University of Milan, offered a glimpse at APL-2 in a different setting: AIHA.
Eligibility required hemoglobin levels of less than 11 g/dL, signs of hemolysis, and positive direct antiglobulin test for IgG and/or complement C3.
Dr. Fattizzo discussed results from five patients with cold agglutinin disease and five patients with C3-positive warm AIHA who had received 56 days of therapy.
Among the five patients with cold agglutinin disease, mean hemoglobin increased from 8.7 g/dL to 12.1 g/dL, while patients with warm C3-positive AIHA had a mean increase from 9.3 g/dL to 11.3 g/dL. As with the PNH study, absolute reticulocyte count, LDH, and indirect bilirubin normalized across all 10 patients.
“Some of the patients included in the trial have already reached more than 48 weeks, something like 64 weeks in the study, and they are still doing well,” Dr. Fattizzo said. “So it really seems that those who are do respond really keep the response with ongoing treatment.”
Nine out of 12 patients with cold agglutinin disease (75%) and 8 out of 9 patients (89%) with warm AIHA experienced adverse events, although these were mostly grade 1 or 2 and deemed unrelated to APL-2 by the investigators.
Five grade 3 adverse events in six patients included oral squamous carcinoma, hemolytic flare, pneumonia, purpura, and acute kidney injury. Five grade 4 adverse events in two patients included high calcium, high creatinine, hypoxia, and hemolytic flare, causing these two patients to withdraw from the study. No grade 3 or 4 adverse events were considered related to APL-2.
“APL-2 appears to be well tolerated and safe,” Dr. Fattizzo said, adding that a phase 3 trial for cold agglutinin disease and C3-positive warm AIHA C3+ is planned.
Both studies are sponsored by Apellis Pharmaceuticals. Dr. Wong and his colleagues reported financial relationships with Alexion Pharmaceuticals, Apellis, Celgene, Janssen, and other companies. Dr. Fattizzo reported having no conflicts of interest.
GLASGOW – APL-2, a complement factor 3 (C3) inhibitor, may be a future treatment option for paroxysmal nocturnal hemoglobinuria (PNH) and autoimmune hemolytic anemia (AIHA), according to investigators from two separate studies.
Early results from the phase 1b PADDOCK trial for PNH and the phase 2 PLAUDIT trial for AIHA showed that APL-2 significantly increased hemoglobin levels, with additional improvements reported in lactate dehydrogenase (LDH), absolute reticulocyte count, and bilirubin. The findings were presented at the annual meeting of the British Society for Haematology.
By blocking C3, APL-2 acts further upstream than approved C5 inhibitors eculizumab and ravulizumab, thereby controlling extravascular hemolysis in addition to intravascular hemolysis. This broader level of control is needed for some patients, the investigators said, such as those with PNH who have inadequate responses to C5 inhibition.
PNH
“Even in PNH patients treated with eculizumab, up to 70% may have suboptimal hemoglobin responses and about 30% may still require blood transfusions,” said lead author of the PADDOCK trial, Raymond Wong, MD, of the Prince of Wales Hospital in Hong Kong.
PNH patients included in the open-label, dose-escalation PADDOCK study had greater than 10% white blood cell clones, LDH that was at least twice the upper limit of normal, at least one transfusion within the past year, a platelet count below 30,000/mm3, and an absolute neutrophil count greater than 500 x 109/L.
Dr. Wong described experiences with a cohort of 20 patients who received 270 mg APL-2 subcutaneously daily for at least 28 days, with the option to continue treatment for up to 2 years thereafter, if desired.
From these 20 patients, 2 patients completed the initial 28-day period but did not elect to continue and 2 patients withdrew because of adverse events (ovarian cancer and severe aplastic anemia), leaving 16 patients in the present analysis. Before treatment, these individuals were transfusion dependent, with an average transfusion rate of 8.7 transfusions per year.
Results showed that mean hemoglobin increased from 8.0 g/dL at baseline to 10.8 g/dL at day 29 and 12.2 g/dL at day 85. LDH dropped 900%, from 2,416 U/L (9 times the upper limit of normal) to 271 U/L (0.9 times the upper limit of normal). Absolute reticulocyte count and bilirubin also normalized.
Overall, these improvements led to a meaningful clinical impact, Dr. Wong said, with fatigue scores improving and most patients becoming transfusion independent on maintenance therapy, with the exception of one patient who developed severe aplastic anemia after 1 year. No significant infections or thromboses occurred.
When asked where APL-2 might fit in with current treatment paradigm, Dr. Wong said that multiple applications for PNH are being investigated, including first-line therapy and after failure of eculizumab.
AIHA
Results from the phase 2 PLAUDIT trial, presented by Bruno Fattizzo, MD, of the University of Milan, offered a glimpse at APL-2 in a different setting: AIHA.
Eligibility required hemoglobin levels of less than 11 g/dL, signs of hemolysis, and positive direct antiglobulin test for IgG and/or complement C3.
Dr. Fattizzo discussed results from five patients with cold agglutinin disease and five patients with C3-positive warm AIHA who had received 56 days of therapy.
Among the five patients with cold agglutinin disease, mean hemoglobin increased from 8.7 g/dL to 12.1 g/dL, while patients with warm C3-positive AIHA had a mean increase from 9.3 g/dL to 11.3 g/dL. As with the PNH study, absolute reticulocyte count, LDH, and indirect bilirubin normalized across all 10 patients.
“Some of the patients included in the trial have already reached more than 48 weeks, something like 64 weeks in the study, and they are still doing well,” Dr. Fattizzo said. “So it really seems that those who are do respond really keep the response with ongoing treatment.”
Nine out of 12 patients with cold agglutinin disease (75%) and 8 out of 9 patients (89%) with warm AIHA experienced adverse events, although these were mostly grade 1 or 2 and deemed unrelated to APL-2 by the investigators.
Five grade 3 adverse events in six patients included oral squamous carcinoma, hemolytic flare, pneumonia, purpura, and acute kidney injury. Five grade 4 adverse events in two patients included high calcium, high creatinine, hypoxia, and hemolytic flare, causing these two patients to withdraw from the study. No grade 3 or 4 adverse events were considered related to APL-2.
“APL-2 appears to be well tolerated and safe,” Dr. Fattizzo said, adding that a phase 3 trial for cold agglutinin disease and C3-positive warm AIHA C3+ is planned.
Both studies are sponsored by Apellis Pharmaceuticals. Dr. Wong and his colleagues reported financial relationships with Alexion Pharmaceuticals, Apellis, Celgene, Janssen, and other companies. Dr. Fattizzo reported having no conflicts of interest.
REPORTING FROM BSH 2019
FDA examines changing donation policies for men who have sex with men
The
At a meeting of the FDA’s Blood Products Advisory Committee, the agency shared the content of the 5-item questionnaire and reviewed the proposed study design with committee members, who were asked to comment – but not vote – on the best path forward for MSM donation policies.
The FDA is “committed to ongoing evaluation of the MSM deferral policy” and remains open to adjusting the policy based on the best available scientific evidence, said Barbee Whitaker, PhD, a lead scientist in the agency’s Office of Emerging and Transfusion Transmitted Disease
After recruiting 2,000 men who have had sex with men at least once during the past 3 months, the study will aim to identify individuals who have very recently become HIV infected, in order to assess the discriminant function of the set of behavioral questions that are proposed in the questionnaire.
The crux of the problem currently, noted Dr. Whitaker, is identifying those individuals who are very recently infected with HIV. Nucleic acid testing has tightened the window of undetectability considerably, but the current 12-month deferral window after men have had sexual contact with other men is designed to ensure safety of the blood supply.
Social justice concerns have been raised about the blanket deferral, said Dr. Whitaker; the behavioral questions in the pilot study will ask about the number of different sexual partners men have had within the past 1, 3, and 12 months and ask about the type of sexual contact (oral sex, or anal penetrative or receptive intercourse). The questionnaire also asks about sex with a partner known to be HIV positive, condom use, and use of pre-exposure prophylaxis (PrEP).
The FDA will ask for proposals to conduct the study with an eye to having sites in such cities as Washington, Atlanta, and Miami, which have high incidences of HIV, to improve chances of early detection.
The behavioral questionnaire is not seen as an immediate replacement for the 12-month deferral policy, the FDA made clear in its briefing documents and in discussion with the committee. Instead, its utility will be in the information gleaned from the pilot study and a follow-on that may include several hundred thousand individuals. These data should provide “population-based evidence upon which to base regulatory decisions to ensure blood safety,” she said.
Donation policies outside the United States
Whether a change in blood donation deferral policies for MSM would be a shortened window or a move toward a behavioral questionnaire is currently not known. Globally, a variety of practices are used for blood screening, said Mindy Goldman, MD, medical director of Canadian Blood Services, who reviewed international perspectives on blood donation for MSM.
“There’s no general consensus on donation deferrals internationally,” she said. Factors influencing policy can include epidemiology, risk analysis, modeling, and history of response to threats in the past.
However, “there’s basically a couple of main approaches” to handling deferrals for MSM, Dr. Goldman said. One is time-based deferral – the strategy used in the United States, as well as Canada, the United Kingdom, Japan, and Australia.
Japan and the U.K. have recently moved to 3-month deferral periods, a figure arrived at by doubling the window period for nucleic acid testing for HIV, roughly, Dr. Goldman said. Early data from the U.K. experience has not shown an increase in HIV rates among donors, or an increase in NAT-only positive donors, she said. An application to move from a 12-month to a 3-month deferral period is pending in Canada.
A strong advantage of time-based deferral as a risk management strategy, Dr. Goldman said, is standardization. “For us, standardization is close to godliness.”
However, she added, “another major limitation is that you’re still deferring all sexually active MSM, including those who are in a stable monogamous relationship from donating. From a justice perspective for the lowest risk population of MSM – they are still being deferred using this type of approach.”
Some nations, such as Spain and Italy, use individual risk assessment via physician-led interviews. These approaches are often not standardized. “There’s no national uniform questionnaire, so there’s less standardization, and more variability between blood centers,” Dr. Goldman said. “So you wind up trying to compare apples with oranges.”
This means the results are harder to evaluate on a national level. However, there appears to be higher residual risk, with HIV rates among first-time donors approaching those of the general population, Dr. Goldman said.
Another strategy, used in France, is a test-retest model, where blood from first-time MSM that initially tests negative for HIV is held until the individual returns for re-testing or an additional donation, with a second negative test. This approach increases operational complexity and cost, noted Dr. Goldman, and because of the short shelf life of platelets, it’s not practical for this blood component.
In general questioning and discussion after this and other background presentations, the committee could agree on one point: this isn’t an easy question.
“I’m increasingly struck by how difficult this problem is,” said committee member Roger Lewis, MD, PhD, professor at the University of California, Los Angeles, and chair of the department of emergency medicine at Harbor-UCLA Medical Center. Regarding just the problem of completing the pilot study, Dr. Lewis commented, “It sounds like it’s going to be impossible to get the data that directly answers the questions.”
Peter Marx, MD, PhD, who directs the FDA’s Center for Biologics Evaluation and Research (CBER), which oversees blood products safety, joined the discussion to acknowledge the difficulty, but underscore the social importance of a careful examination of the current MSM donation policy.
“We understand the issues here…. With all due respect to our European colleagues, there’s not enough data. That’s the point of this study; we also know that the U.S. has a very different epidemiology of HIV than the U.K. and a lot of other places,” Dr. Marx said. “The pilot study is a way to get some data where we might be able to get away from a time-based deferral. The LGBT community finds any time-based deferral discriminatory.”
Pathogen reduction technology
The committee heard a proposal for a completely different strategy during its afternoon session: pathogen reduction technology (PRT) holds promise to achieve virtual elimination of HIV and other pathogens from donated blood products.
The FDA is reviewing a variance request from the nonprofit blood donation organization Bloodworks Northwest organization to use PRT for apheresis platelet donations from MSM who would otherwise be deferred because of sexual activity within the 12-month deferral window.
James AuBuchon, MD, president of Bloodworks Northwest, explained that his organization takes in about 225,000 donations annually. The variance sought would use the FDA-approved INTERCEPT device to achieve pathogen reduction for donations that meet all requirements except the MSM deferral, and that would still undergo all relevant transfusion transmitted infection testing.
The INTERCEPT device uses amotosalen, which intercalates with DNA and RNA, inactivating it after exposure to ultraviolet A light. Amotosalen is then removed from the blood product before administration. The pathogen reduction activity doesn’t interfere with platelets or plasma, and is active against a wide range of viruses, bacteria, and fungal pathogens, explained Dr. AuBuchon, who is also a professor of hematology at the University of Washington, Seattle.
Dr. AuBuchon walked the committee through procedures designed to flag donors for PRT platelet apheresis, and to ensure these donations receive the intended PRT treatment. Platelets were chosen for this variance request, he explained, because demand outstrips supply. “We are all spending additional time and resources in recruiting a new framework and demographic, and it is exceedingly difficult to keep enough donors coming through the door,” he said. “Our platelet utilization climbs continually – it’s up 15% in the last 4 years.”
Committee members circled around the idea that all risk can’t be eliminated, even with the highly effective PRT technology. But the risk is exceedingly low, said committee chair Richard Kaufman, MD, medical director of the adult transfusion service at Brigham and Women’s Hospital, Boston. “It’s not possible to get rid of the window. We can kind of hammer down the risk by shrinking down the window by using incredibly sensitive tests. But that risk continues to exist. Pathogen reduction can take care of that residual risk…. So what’s left is really quite a low risk,” Dr. Kaufman said.
Susan Stramer, PhD, vice president of scientific affairs for the American Red Cross, concurred, noting that pathogen reduction techniques are already in use for many other blood products, particularly within the plasma industry.
Wrapping up, Dr. Kaufman asked individual committee members to summarize their position on the variance request, though the FDA had not placed a voting question before the committee. Consensus in the room was that this real-world examination of PRT could point to a path to expanding the donor pool while maintaining patient safety – a concern all agreed was paramount.
The FDA usually follows the recommendations of its committees.
The
At a meeting of the FDA’s Blood Products Advisory Committee, the agency shared the content of the 5-item questionnaire and reviewed the proposed study design with committee members, who were asked to comment – but not vote – on the best path forward for MSM donation policies.
The FDA is “committed to ongoing evaluation of the MSM deferral policy” and remains open to adjusting the policy based on the best available scientific evidence, said Barbee Whitaker, PhD, a lead scientist in the agency’s Office of Emerging and Transfusion Transmitted Disease
After recruiting 2,000 men who have had sex with men at least once during the past 3 months, the study will aim to identify individuals who have very recently become HIV infected, in order to assess the discriminant function of the set of behavioral questions that are proposed in the questionnaire.
The crux of the problem currently, noted Dr. Whitaker, is identifying those individuals who are very recently infected with HIV. Nucleic acid testing has tightened the window of undetectability considerably, but the current 12-month deferral window after men have had sexual contact with other men is designed to ensure safety of the blood supply.
Social justice concerns have been raised about the blanket deferral, said Dr. Whitaker; the behavioral questions in the pilot study will ask about the number of different sexual partners men have had within the past 1, 3, and 12 months and ask about the type of sexual contact (oral sex, or anal penetrative or receptive intercourse). The questionnaire also asks about sex with a partner known to be HIV positive, condom use, and use of pre-exposure prophylaxis (PrEP).
The FDA will ask for proposals to conduct the study with an eye to having sites in such cities as Washington, Atlanta, and Miami, which have high incidences of HIV, to improve chances of early detection.
The behavioral questionnaire is not seen as an immediate replacement for the 12-month deferral policy, the FDA made clear in its briefing documents and in discussion with the committee. Instead, its utility will be in the information gleaned from the pilot study and a follow-on that may include several hundred thousand individuals. These data should provide “population-based evidence upon which to base regulatory decisions to ensure blood safety,” she said.
Donation policies outside the United States
Whether a change in blood donation deferral policies for MSM would be a shortened window or a move toward a behavioral questionnaire is currently not known. Globally, a variety of practices are used for blood screening, said Mindy Goldman, MD, medical director of Canadian Blood Services, who reviewed international perspectives on blood donation for MSM.
“There’s no general consensus on donation deferrals internationally,” she said. Factors influencing policy can include epidemiology, risk analysis, modeling, and history of response to threats in the past.
However, “there’s basically a couple of main approaches” to handling deferrals for MSM, Dr. Goldman said. One is time-based deferral – the strategy used in the United States, as well as Canada, the United Kingdom, Japan, and Australia.
Japan and the U.K. have recently moved to 3-month deferral periods, a figure arrived at by doubling the window period for nucleic acid testing for HIV, roughly, Dr. Goldman said. Early data from the U.K. experience has not shown an increase in HIV rates among donors, or an increase in NAT-only positive donors, she said. An application to move from a 12-month to a 3-month deferral period is pending in Canada.
A strong advantage of time-based deferral as a risk management strategy, Dr. Goldman said, is standardization. “For us, standardization is close to godliness.”
However, she added, “another major limitation is that you’re still deferring all sexually active MSM, including those who are in a stable monogamous relationship from donating. From a justice perspective for the lowest risk population of MSM – they are still being deferred using this type of approach.”
Some nations, such as Spain and Italy, use individual risk assessment via physician-led interviews. These approaches are often not standardized. “There’s no national uniform questionnaire, so there’s less standardization, and more variability between blood centers,” Dr. Goldman said. “So you wind up trying to compare apples with oranges.”
This means the results are harder to evaluate on a national level. However, there appears to be higher residual risk, with HIV rates among first-time donors approaching those of the general population, Dr. Goldman said.
Another strategy, used in France, is a test-retest model, where blood from first-time MSM that initially tests negative for HIV is held until the individual returns for re-testing or an additional donation, with a second negative test. This approach increases operational complexity and cost, noted Dr. Goldman, and because of the short shelf life of platelets, it’s not practical for this blood component.
In general questioning and discussion after this and other background presentations, the committee could agree on one point: this isn’t an easy question.
“I’m increasingly struck by how difficult this problem is,” said committee member Roger Lewis, MD, PhD, professor at the University of California, Los Angeles, and chair of the department of emergency medicine at Harbor-UCLA Medical Center. Regarding just the problem of completing the pilot study, Dr. Lewis commented, “It sounds like it’s going to be impossible to get the data that directly answers the questions.”
Peter Marx, MD, PhD, who directs the FDA’s Center for Biologics Evaluation and Research (CBER), which oversees blood products safety, joined the discussion to acknowledge the difficulty, but underscore the social importance of a careful examination of the current MSM donation policy.
“We understand the issues here…. With all due respect to our European colleagues, there’s not enough data. That’s the point of this study; we also know that the U.S. has a very different epidemiology of HIV than the U.K. and a lot of other places,” Dr. Marx said. “The pilot study is a way to get some data where we might be able to get away from a time-based deferral. The LGBT community finds any time-based deferral discriminatory.”
Pathogen reduction technology
The committee heard a proposal for a completely different strategy during its afternoon session: pathogen reduction technology (PRT) holds promise to achieve virtual elimination of HIV and other pathogens from donated blood products.
The FDA is reviewing a variance request from the nonprofit blood donation organization Bloodworks Northwest organization to use PRT for apheresis platelet donations from MSM who would otherwise be deferred because of sexual activity within the 12-month deferral window.
James AuBuchon, MD, president of Bloodworks Northwest, explained that his organization takes in about 225,000 donations annually. The variance sought would use the FDA-approved INTERCEPT device to achieve pathogen reduction for donations that meet all requirements except the MSM deferral, and that would still undergo all relevant transfusion transmitted infection testing.
The INTERCEPT device uses amotosalen, which intercalates with DNA and RNA, inactivating it after exposure to ultraviolet A light. Amotosalen is then removed from the blood product before administration. The pathogen reduction activity doesn’t interfere with platelets or plasma, and is active against a wide range of viruses, bacteria, and fungal pathogens, explained Dr. AuBuchon, who is also a professor of hematology at the University of Washington, Seattle.
Dr. AuBuchon walked the committee through procedures designed to flag donors for PRT platelet apheresis, and to ensure these donations receive the intended PRT treatment. Platelets were chosen for this variance request, he explained, because demand outstrips supply. “We are all spending additional time and resources in recruiting a new framework and demographic, and it is exceedingly difficult to keep enough donors coming through the door,” he said. “Our platelet utilization climbs continually – it’s up 15% in the last 4 years.”
Committee members circled around the idea that all risk can’t be eliminated, even with the highly effective PRT technology. But the risk is exceedingly low, said committee chair Richard Kaufman, MD, medical director of the adult transfusion service at Brigham and Women’s Hospital, Boston. “It’s not possible to get rid of the window. We can kind of hammer down the risk by shrinking down the window by using incredibly sensitive tests. But that risk continues to exist. Pathogen reduction can take care of that residual risk…. So what’s left is really quite a low risk,” Dr. Kaufman said.
Susan Stramer, PhD, vice president of scientific affairs for the American Red Cross, concurred, noting that pathogen reduction techniques are already in use for many other blood products, particularly within the plasma industry.
Wrapping up, Dr. Kaufman asked individual committee members to summarize their position on the variance request, though the FDA had not placed a voting question before the committee. Consensus in the room was that this real-world examination of PRT could point to a path to expanding the donor pool while maintaining patient safety – a concern all agreed was paramount.
The FDA usually follows the recommendations of its committees.
The
At a meeting of the FDA’s Blood Products Advisory Committee, the agency shared the content of the 5-item questionnaire and reviewed the proposed study design with committee members, who were asked to comment – but not vote – on the best path forward for MSM donation policies.
The FDA is “committed to ongoing evaluation of the MSM deferral policy” and remains open to adjusting the policy based on the best available scientific evidence, said Barbee Whitaker, PhD, a lead scientist in the agency’s Office of Emerging and Transfusion Transmitted Disease
After recruiting 2,000 men who have had sex with men at least once during the past 3 months, the study will aim to identify individuals who have very recently become HIV infected, in order to assess the discriminant function of the set of behavioral questions that are proposed in the questionnaire.
The crux of the problem currently, noted Dr. Whitaker, is identifying those individuals who are very recently infected with HIV. Nucleic acid testing has tightened the window of undetectability considerably, but the current 12-month deferral window after men have had sexual contact with other men is designed to ensure safety of the blood supply.
Social justice concerns have been raised about the blanket deferral, said Dr. Whitaker; the behavioral questions in the pilot study will ask about the number of different sexual partners men have had within the past 1, 3, and 12 months and ask about the type of sexual contact (oral sex, or anal penetrative or receptive intercourse). The questionnaire also asks about sex with a partner known to be HIV positive, condom use, and use of pre-exposure prophylaxis (PrEP).
The FDA will ask for proposals to conduct the study with an eye to having sites in such cities as Washington, Atlanta, and Miami, which have high incidences of HIV, to improve chances of early detection.
The behavioral questionnaire is not seen as an immediate replacement for the 12-month deferral policy, the FDA made clear in its briefing documents and in discussion with the committee. Instead, its utility will be in the information gleaned from the pilot study and a follow-on that may include several hundred thousand individuals. These data should provide “population-based evidence upon which to base regulatory decisions to ensure blood safety,” she said.
Donation policies outside the United States
Whether a change in blood donation deferral policies for MSM would be a shortened window or a move toward a behavioral questionnaire is currently not known. Globally, a variety of practices are used for blood screening, said Mindy Goldman, MD, medical director of Canadian Blood Services, who reviewed international perspectives on blood donation for MSM.
“There’s no general consensus on donation deferrals internationally,” she said. Factors influencing policy can include epidemiology, risk analysis, modeling, and history of response to threats in the past.
However, “there’s basically a couple of main approaches” to handling deferrals for MSM, Dr. Goldman said. One is time-based deferral – the strategy used in the United States, as well as Canada, the United Kingdom, Japan, and Australia.
Japan and the U.K. have recently moved to 3-month deferral periods, a figure arrived at by doubling the window period for nucleic acid testing for HIV, roughly, Dr. Goldman said. Early data from the U.K. experience has not shown an increase in HIV rates among donors, or an increase in NAT-only positive donors, she said. An application to move from a 12-month to a 3-month deferral period is pending in Canada.
A strong advantage of time-based deferral as a risk management strategy, Dr. Goldman said, is standardization. “For us, standardization is close to godliness.”
However, she added, “another major limitation is that you’re still deferring all sexually active MSM, including those who are in a stable monogamous relationship from donating. From a justice perspective for the lowest risk population of MSM – they are still being deferred using this type of approach.”
Some nations, such as Spain and Italy, use individual risk assessment via physician-led interviews. These approaches are often not standardized. “There’s no national uniform questionnaire, so there’s less standardization, and more variability between blood centers,” Dr. Goldman said. “So you wind up trying to compare apples with oranges.”
This means the results are harder to evaluate on a national level. However, there appears to be higher residual risk, with HIV rates among first-time donors approaching those of the general population, Dr. Goldman said.
Another strategy, used in France, is a test-retest model, where blood from first-time MSM that initially tests negative for HIV is held until the individual returns for re-testing or an additional donation, with a second negative test. This approach increases operational complexity and cost, noted Dr. Goldman, and because of the short shelf life of platelets, it’s not practical for this blood component.
In general questioning and discussion after this and other background presentations, the committee could agree on one point: this isn’t an easy question.
“I’m increasingly struck by how difficult this problem is,” said committee member Roger Lewis, MD, PhD, professor at the University of California, Los Angeles, and chair of the department of emergency medicine at Harbor-UCLA Medical Center. Regarding just the problem of completing the pilot study, Dr. Lewis commented, “It sounds like it’s going to be impossible to get the data that directly answers the questions.”
Peter Marx, MD, PhD, who directs the FDA’s Center for Biologics Evaluation and Research (CBER), which oversees blood products safety, joined the discussion to acknowledge the difficulty, but underscore the social importance of a careful examination of the current MSM donation policy.
“We understand the issues here…. With all due respect to our European colleagues, there’s not enough data. That’s the point of this study; we also know that the U.S. has a very different epidemiology of HIV than the U.K. and a lot of other places,” Dr. Marx said. “The pilot study is a way to get some data where we might be able to get away from a time-based deferral. The LGBT community finds any time-based deferral discriminatory.”
Pathogen reduction technology
The committee heard a proposal for a completely different strategy during its afternoon session: pathogen reduction technology (PRT) holds promise to achieve virtual elimination of HIV and other pathogens from donated blood products.
The FDA is reviewing a variance request from the nonprofit blood donation organization Bloodworks Northwest organization to use PRT for apheresis platelet donations from MSM who would otherwise be deferred because of sexual activity within the 12-month deferral window.
James AuBuchon, MD, president of Bloodworks Northwest, explained that his organization takes in about 225,000 donations annually. The variance sought would use the FDA-approved INTERCEPT device to achieve pathogen reduction for donations that meet all requirements except the MSM deferral, and that would still undergo all relevant transfusion transmitted infection testing.
The INTERCEPT device uses amotosalen, which intercalates with DNA and RNA, inactivating it after exposure to ultraviolet A light. Amotosalen is then removed from the blood product before administration. The pathogen reduction activity doesn’t interfere with platelets or plasma, and is active against a wide range of viruses, bacteria, and fungal pathogens, explained Dr. AuBuchon, who is also a professor of hematology at the University of Washington, Seattle.
Dr. AuBuchon walked the committee through procedures designed to flag donors for PRT platelet apheresis, and to ensure these donations receive the intended PRT treatment. Platelets were chosen for this variance request, he explained, because demand outstrips supply. “We are all spending additional time and resources in recruiting a new framework and demographic, and it is exceedingly difficult to keep enough donors coming through the door,” he said. “Our platelet utilization climbs continually – it’s up 15% in the last 4 years.”
Committee members circled around the idea that all risk can’t be eliminated, even with the highly effective PRT technology. But the risk is exceedingly low, said committee chair Richard Kaufman, MD, medical director of the adult transfusion service at Brigham and Women’s Hospital, Boston. “It’s not possible to get rid of the window. We can kind of hammer down the risk by shrinking down the window by using incredibly sensitive tests. But that risk continues to exist. Pathogen reduction can take care of that residual risk…. So what’s left is really quite a low risk,” Dr. Kaufman said.
Susan Stramer, PhD, vice president of scientific affairs for the American Red Cross, concurred, noting that pathogen reduction techniques are already in use for many other blood products, particularly within the plasma industry.
Wrapping up, Dr. Kaufman asked individual committee members to summarize their position on the variance request, though the FDA had not placed a voting question before the committee. Consensus in the room was that this real-world examination of PRT could point to a path to expanding the donor pool while maintaining patient safety – a concern all agreed was paramount.
The FDA usually follows the recommendations of its committees.
FROM AN FDA ADVISORY COMMITTEE MEETING
FDA committee advises status quo for blood supply Zika testing
Most members of a Food and Drug Administration advisory committee considered that data support maintaining current testing protocols for Zika virus in the blood donor pool. However, committee discussion entertained the idea of revisiting testing strategies after another year or 2 of Zika virus epidemiological data are available.
In its last guidance regarding Zika virus testing, issued in July 2018, the FDA recommended that either minipool nucleic acid testing (MP NAT) or individual donor (ID) NAT be used to screen for Zika virus. Current guidance still requires conversion to all-ID NAT “when certain threshold conditions are met that indicate an increased risk of suspected mosquito-borne transmission in a defined geographic collection area.”
In the first of three separate votes, 11 of 15 voting members of the FDA’s Blood Products Advisory Committee (BPAC) answered in the affirmative to the question of whether available data support continuing the status quo for Zika testing. Committee members then were asked to weigh whether current data support scaling back to a regional testing strategy targeting at-risk areas. Here, six committee members answered in the affirmative, and nine in the negative.
Just one committee member, F. Blaine Hollinger, MD, voted in favor of the third option, elimination of all Zika virus testing without reintroducing donor screening for risk factors in risk-free areas pending another outbreak in the United States. Dr. Hollinger is a professor of virology and microbiology at Baylor College of Medicine, Houston.
The committee as whole wasn’t swayed by a line of questioning put forward by chairman Richard Kaufman, MD. “I will be the devil’s advocate a little bit: We learned that there have been zero confirmed positives from blood donors for the past year. Would anyone be comfortable with just stopping screening of donors?” asked Dr. Kaufman, medical director of the adult transfusion service at Brigham and Women’s Hospital, Boston.
A wide-ranging morning of presentations put data regarding historical trends and current global Zika hot spots in front of the committee. Current upticks in infection rates in northwest Mexico and in some states in India were areas of concern, given North American travel patterns, noted speaker Marc Fisher, MD, of the Center for Disease Control and Prevention’s Arboviral Disease Branch (Fort Collins, Colo.) “We’re going to see sporadic outbreaks; it’s hard to predict the future,” he said. “The new outbreak in India raises concerns.”
Briefing information from the FDA explained that Zika virus local transmission peaked in the United States in late summer of 2016. More than 5,000 cases were reported in the United States and over 36,000 in Puerto Rico. This has plummeted to 220 in 2018, with about two-thirds of these cases occurring in the territories, mostly (97%) from Puerto Rico across all 3 years.
Zika viremic blood donors dropped by an order of magnitude yearly, totaling 363 in 2016, 38 in 2017, and just 3 in 2018. Of the 363 detected in 2016, 96% came from Puerto Rico or Florida, noted Dr. Fisher.
The number of suspected and confirmed cases in the Americas overall has also dropped from over 650,000 in 2016 to under 30,000 in 2018, with most cases in 2018 being suspected rather than laboratory confirmed. In contrast to testing conducted in North America, few cases in much of Central and South America were laboratory confirmed.
Asymptomatic infections have occurred in blood donors, said the FDA, with 1.8% of blood donations in Puerto Rico testing positive for Zika virus during the peak of the outbreak. Transmission by transfusion is thought to have occurred in Brazil.
Although Zika virus infections have plummeted in the United States and worldwide, prevalence and rates of local transmission are unpredictable, said the FDA, which pointed to sporadic increases in autochthonous transmission of viruses such as dengue and chikungunya that are carried by the same mosquito vector as Zika.
Some of the committee’s discussion centered around finding a way to carve out protection for those most harmed by Zika virus – pregnant women and their fetuses. Martin Schreiber, MD, professor of surgery at Oregon Health and Sciences University, Portland, proposed a point-of-care testing strategy in which only blood destined for pregnant women would be tested for Zika virus. Dr. Schreiber, a trauma surgeon, put forward the rationale that Zika virus causes harm almost exclusively to fetuses, except for rare cases of Guillain-Barré syndrome.
In response, Dr. Kaufman pointed out that with rare exceptions for some bacterial testing, all testing is done from samples taken at the point of donation. The supply chain for donor blood is not set up to accommodate point-of-care testing, he said.
Answering questions about another targeted strategy – maintaining a separate, Zika-tested supply of blood for pregnant women – Susan Stramer, PhD, vice president of scientific affairs for the American Red Cross, said, “Most hospitals do not want, and are very adamant against, carrying a dual inventory.”
Ultimately, the committee’s discussion swung toward the realization that it may be too soon after the recent spike in U.S. Zika cases to plot the best course for ongoing testing strategies. “We are at the tail end of a waning epidemic. ... I think it would probably be a pretty easy question for the committee and for the agency if we actually had some way of having a crystal ball and knowing that the current trend was likely to continue,” said Roger Lewis, MD, PhD, professor at the University of California, Los Angeles, and chair of the department of emergency medicine at Harbor-UCLA Medical Center.
“I think that is not the question,” he went on. “I think the question is, What is the optimal strategy if we have no idea if that tail is going to continue in this current trend. ... And that maybe the committee ought to be thinking about what is the right strategy for the next 2 years – with an underlying assumption that this is a question that can be brought back as we learn more about how this disease behaves.”
The FDA usually follows the recommendations of its advisory committees.
Most members of a Food and Drug Administration advisory committee considered that data support maintaining current testing protocols for Zika virus in the blood donor pool. However, committee discussion entertained the idea of revisiting testing strategies after another year or 2 of Zika virus epidemiological data are available.
In its last guidance regarding Zika virus testing, issued in July 2018, the FDA recommended that either minipool nucleic acid testing (MP NAT) or individual donor (ID) NAT be used to screen for Zika virus. Current guidance still requires conversion to all-ID NAT “when certain threshold conditions are met that indicate an increased risk of suspected mosquito-borne transmission in a defined geographic collection area.”
In the first of three separate votes, 11 of 15 voting members of the FDA’s Blood Products Advisory Committee (BPAC) answered in the affirmative to the question of whether available data support continuing the status quo for Zika testing. Committee members then were asked to weigh whether current data support scaling back to a regional testing strategy targeting at-risk areas. Here, six committee members answered in the affirmative, and nine in the negative.
Just one committee member, F. Blaine Hollinger, MD, voted in favor of the third option, elimination of all Zika virus testing without reintroducing donor screening for risk factors in risk-free areas pending another outbreak in the United States. Dr. Hollinger is a professor of virology and microbiology at Baylor College of Medicine, Houston.
The committee as whole wasn’t swayed by a line of questioning put forward by chairman Richard Kaufman, MD. “I will be the devil’s advocate a little bit: We learned that there have been zero confirmed positives from blood donors for the past year. Would anyone be comfortable with just stopping screening of donors?” asked Dr. Kaufman, medical director of the adult transfusion service at Brigham and Women’s Hospital, Boston.
A wide-ranging morning of presentations put data regarding historical trends and current global Zika hot spots in front of the committee. Current upticks in infection rates in northwest Mexico and in some states in India were areas of concern, given North American travel patterns, noted speaker Marc Fisher, MD, of the Center for Disease Control and Prevention’s Arboviral Disease Branch (Fort Collins, Colo.) “We’re going to see sporadic outbreaks; it’s hard to predict the future,” he said. “The new outbreak in India raises concerns.”
Briefing information from the FDA explained that Zika virus local transmission peaked in the United States in late summer of 2016. More than 5,000 cases were reported in the United States and over 36,000 in Puerto Rico. This has plummeted to 220 in 2018, with about two-thirds of these cases occurring in the territories, mostly (97%) from Puerto Rico across all 3 years.
Zika viremic blood donors dropped by an order of magnitude yearly, totaling 363 in 2016, 38 in 2017, and just 3 in 2018. Of the 363 detected in 2016, 96% came from Puerto Rico or Florida, noted Dr. Fisher.
The number of suspected and confirmed cases in the Americas overall has also dropped from over 650,000 in 2016 to under 30,000 in 2018, with most cases in 2018 being suspected rather than laboratory confirmed. In contrast to testing conducted in North America, few cases in much of Central and South America were laboratory confirmed.
Asymptomatic infections have occurred in blood donors, said the FDA, with 1.8% of blood donations in Puerto Rico testing positive for Zika virus during the peak of the outbreak. Transmission by transfusion is thought to have occurred in Brazil.
Although Zika virus infections have plummeted in the United States and worldwide, prevalence and rates of local transmission are unpredictable, said the FDA, which pointed to sporadic increases in autochthonous transmission of viruses such as dengue and chikungunya that are carried by the same mosquito vector as Zika.
Some of the committee’s discussion centered around finding a way to carve out protection for those most harmed by Zika virus – pregnant women and their fetuses. Martin Schreiber, MD, professor of surgery at Oregon Health and Sciences University, Portland, proposed a point-of-care testing strategy in which only blood destined for pregnant women would be tested for Zika virus. Dr. Schreiber, a trauma surgeon, put forward the rationale that Zika virus causes harm almost exclusively to fetuses, except for rare cases of Guillain-Barré syndrome.
In response, Dr. Kaufman pointed out that with rare exceptions for some bacterial testing, all testing is done from samples taken at the point of donation. The supply chain for donor blood is not set up to accommodate point-of-care testing, he said.
Answering questions about another targeted strategy – maintaining a separate, Zika-tested supply of blood for pregnant women – Susan Stramer, PhD, vice president of scientific affairs for the American Red Cross, said, “Most hospitals do not want, and are very adamant against, carrying a dual inventory.”
Ultimately, the committee’s discussion swung toward the realization that it may be too soon after the recent spike in U.S. Zika cases to plot the best course for ongoing testing strategies. “We are at the tail end of a waning epidemic. ... I think it would probably be a pretty easy question for the committee and for the agency if we actually had some way of having a crystal ball and knowing that the current trend was likely to continue,” said Roger Lewis, MD, PhD, professor at the University of California, Los Angeles, and chair of the department of emergency medicine at Harbor-UCLA Medical Center.
“I think that is not the question,” he went on. “I think the question is, What is the optimal strategy if we have no idea if that tail is going to continue in this current trend. ... And that maybe the committee ought to be thinking about what is the right strategy for the next 2 years – with an underlying assumption that this is a question that can be brought back as we learn more about how this disease behaves.”
The FDA usually follows the recommendations of its advisory committees.
Most members of a Food and Drug Administration advisory committee considered that data support maintaining current testing protocols for Zika virus in the blood donor pool. However, committee discussion entertained the idea of revisiting testing strategies after another year or 2 of Zika virus epidemiological data are available.
In its last guidance regarding Zika virus testing, issued in July 2018, the FDA recommended that either minipool nucleic acid testing (MP NAT) or individual donor (ID) NAT be used to screen for Zika virus. Current guidance still requires conversion to all-ID NAT “when certain threshold conditions are met that indicate an increased risk of suspected mosquito-borne transmission in a defined geographic collection area.”
In the first of three separate votes, 11 of 15 voting members of the FDA’s Blood Products Advisory Committee (BPAC) answered in the affirmative to the question of whether available data support continuing the status quo for Zika testing. Committee members then were asked to weigh whether current data support scaling back to a regional testing strategy targeting at-risk areas. Here, six committee members answered in the affirmative, and nine in the negative.
Just one committee member, F. Blaine Hollinger, MD, voted in favor of the third option, elimination of all Zika virus testing without reintroducing donor screening for risk factors in risk-free areas pending another outbreak in the United States. Dr. Hollinger is a professor of virology and microbiology at Baylor College of Medicine, Houston.
The committee as whole wasn’t swayed by a line of questioning put forward by chairman Richard Kaufman, MD. “I will be the devil’s advocate a little bit: We learned that there have been zero confirmed positives from blood donors for the past year. Would anyone be comfortable with just stopping screening of donors?” asked Dr. Kaufman, medical director of the adult transfusion service at Brigham and Women’s Hospital, Boston.
A wide-ranging morning of presentations put data regarding historical trends and current global Zika hot spots in front of the committee. Current upticks in infection rates in northwest Mexico and in some states in India were areas of concern, given North American travel patterns, noted speaker Marc Fisher, MD, of the Center for Disease Control and Prevention’s Arboviral Disease Branch (Fort Collins, Colo.) “We’re going to see sporadic outbreaks; it’s hard to predict the future,” he said. “The new outbreak in India raises concerns.”
Briefing information from the FDA explained that Zika virus local transmission peaked in the United States in late summer of 2016. More than 5,000 cases were reported in the United States and over 36,000 in Puerto Rico. This has plummeted to 220 in 2018, with about two-thirds of these cases occurring in the territories, mostly (97%) from Puerto Rico across all 3 years.
Zika viremic blood donors dropped by an order of magnitude yearly, totaling 363 in 2016, 38 in 2017, and just 3 in 2018. Of the 363 detected in 2016, 96% came from Puerto Rico or Florida, noted Dr. Fisher.
The number of suspected and confirmed cases in the Americas overall has also dropped from over 650,000 in 2016 to under 30,000 in 2018, with most cases in 2018 being suspected rather than laboratory confirmed. In contrast to testing conducted in North America, few cases in much of Central and South America were laboratory confirmed.
Asymptomatic infections have occurred in blood donors, said the FDA, with 1.8% of blood donations in Puerto Rico testing positive for Zika virus during the peak of the outbreak. Transmission by transfusion is thought to have occurred in Brazil.
Although Zika virus infections have plummeted in the United States and worldwide, prevalence and rates of local transmission are unpredictable, said the FDA, which pointed to sporadic increases in autochthonous transmission of viruses such as dengue and chikungunya that are carried by the same mosquito vector as Zika.
Some of the committee’s discussion centered around finding a way to carve out protection for those most harmed by Zika virus – pregnant women and their fetuses. Martin Schreiber, MD, professor of surgery at Oregon Health and Sciences University, Portland, proposed a point-of-care testing strategy in which only blood destined for pregnant women would be tested for Zika virus. Dr. Schreiber, a trauma surgeon, put forward the rationale that Zika virus causes harm almost exclusively to fetuses, except for rare cases of Guillain-Barré syndrome.
In response, Dr. Kaufman pointed out that with rare exceptions for some bacterial testing, all testing is done from samples taken at the point of donation. The supply chain for donor blood is not set up to accommodate point-of-care testing, he said.
Answering questions about another targeted strategy – maintaining a separate, Zika-tested supply of blood for pregnant women – Susan Stramer, PhD, vice president of scientific affairs for the American Red Cross, said, “Most hospitals do not want, and are very adamant against, carrying a dual inventory.”
Ultimately, the committee’s discussion swung toward the realization that it may be too soon after the recent spike in U.S. Zika cases to plot the best course for ongoing testing strategies. “We are at the tail end of a waning epidemic. ... I think it would probably be a pretty easy question for the committee and for the agency if we actually had some way of having a crystal ball and knowing that the current trend was likely to continue,” said Roger Lewis, MD, PhD, professor at the University of California, Los Angeles, and chair of the department of emergency medicine at Harbor-UCLA Medical Center.
“I think that is not the question,” he went on. “I think the question is, What is the optimal strategy if we have no idea if that tail is going to continue in this current trend. ... And that maybe the committee ought to be thinking about what is the right strategy for the next 2 years – with an underlying assumption that this is a question that can be brought back as we learn more about how this disease behaves.”
The FDA usually follows the recommendations of its advisory committees.
Novel transplant regimen improves survival in primary immunodeficiency
HOUSTON – Allogeneic hematopoietic stem cell transplantation (allo-HCT) following a novel reduced-intensity conditioning regimen was largely successful in a heterogeneous cohort of 29 adults and children with primary immunodeficiency in a prospective clinical trial.
At 1 year after transplant, overall survival was 98% and the estimated graft failure–free and graft-versus-host disease (GVHD)–free survival was 82% among the participants, who had various underlying primary immunodeficiencies (PIDs), Dimana Dimitrova, MD, reported at the Transplantation and Cellular Therapy Meetings.
GVHD-free survival was defined in this National Institutes of Health study as the absence of steroid-refractory grade 3-4 acute GVHD and chronic GVHD, noted Dr. Dimitrova of the NIH.
All patients, including 19 adults and 10 children (median age, 25 years), received a serotherapy-free, radiation-free, reduced-intensity conditioning regimen designed to optimize immune reconstitution, minimize toxicity and GVHD, reduce the risk of infectious complications, and enable successful use of alternative donors.
The conditioning platform included pentostatin on day –11 and day –7 at 4 mg/m2 along with 8 days of low-dose cyclophosphamide and 2 days of pharmacokinetically dosed busulfan at 4,600 mmol/min. GVHD prophylaxis included posttransplantation cyclophosphamide, mycophenolate mofetil (MMF), and sirolimus.
All patients received T cell–replete bone marrow or peripheral blood stem cell allografts; 72% received alternative donor grafts, Dr. Dimitrova said.
Two patients died, including one with bacterial sepsis and invasive aspergillosis who died on day +44 and one with presumed viral encephalitis who died on day +110. The patients were high risk overall (median HCT–comorbidity index score of 3, with a range of 0-11), and the two who died had HCT-CI scores of 6 and 8, respectively.
An additional accidental death occurred at 18 months after transplant “in the setting of continued remission, good graft function, and no transplant-related complications,” she said.
Neutrophil recovery occurred at a median of 17 days after transplant; three patients experienced graft failure, including one primary failure with autologous recovery on day +14 and two secondary graft failures.
“Two patients with known underlying difficult-to-engraft diseases required second transplants using different nonmyeloabalative platforms, and nevertheless required donor lymphocyte infusions to avoid threatened secondary graft failure,” she said. “The third patient actually had sufficiently improved infectious disease control and has not needed a second transplant to date.”
Overall GVHD incidence using the novel platform has been extremely low, she said, noting that 14% of patients had grade 2-4 GVHD and 3% had grade 3-4 acute GVHD. There was no steroid-refractory GVHD or chronic GVHD.
Among the infectious complications, other than those that led to the two deaths, were cytomegalovirus reactivation in 7 of 16 patients at risk, BK virus–associated hemorrhagic cystitis in 19 of 22 patients at risk, and a suspected case of viral cardiomyopathy that ultimately resolved.
“Importantly, although many patients had Epstein-Barr virus [EBV] control issues prior to transplant, no patients received preemptive EBV-directed therapy, and no patients had EBV-PTLD [posttransplant lymphoproliferative disorder],” she said.
Additionally, blood stream infections were detected in five patients, there were two cases of confirmed aspergillosis, and one child developed cutaneous candidiasis. Other complications and toxicities appeared to relate to underlying pretransplant issues in the affected organ or exuberant immune responses to existing infection.
“Phenotype reversal was evident to some degree in all evaluable patients, even in those with mixed chimerism or unknown underlying genetic defect,” Dr. Dimitrova said.
All 10 patients with malignancy or lymphoproliferative disease as an additional indication for allo-HCT remain in remission, and most patients who required immunoglobulin replacement therapy prior to transplant have been able to discontinue it, she noted.
The findings of this study are of note, because while it has been known for decades that allo-HCT is a potentially curative therapy for patients with PIDs that arise from defects in cells of hematopoietic origin, it frequently fails because of complicating factors or is not an option, Dr. Dimitrova said.
“These patients will often enter transplant with multiple comorbidities and disease sequelae, particularly as diagnosis of PIDs increases in older children and adults following years of illness,” she explained, adding that related donor options may be limited if family members are also affected.
For this reason, and with the goal of improving access to allo-HCT to all who require it, the novel conditioning platform used in this study was developed.
The platform was well tolerated overall, Dr. Dimitrova said, emphasizing the “notably low” GVHD rates.
“Currently we are investigating reduced MMF with the goal of promoting earlier immune reconstitution, and a separate protocol has opened that includes several modifications to this platform aimed at patients with increased risk of graft failure who may not tolerate mixed chimerism early on,” she said, noting that both protocols are currently enrolling.
The meeting was held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
Dr. Dimitrova reported having no financial disclosures.
SOURCE: Dimitrova D et al. TCT 2019, Abstract 54.
HOUSTON – Allogeneic hematopoietic stem cell transplantation (allo-HCT) following a novel reduced-intensity conditioning regimen was largely successful in a heterogeneous cohort of 29 adults and children with primary immunodeficiency in a prospective clinical trial.
At 1 year after transplant, overall survival was 98% and the estimated graft failure–free and graft-versus-host disease (GVHD)–free survival was 82% among the participants, who had various underlying primary immunodeficiencies (PIDs), Dimana Dimitrova, MD, reported at the Transplantation and Cellular Therapy Meetings.
GVHD-free survival was defined in this National Institutes of Health study as the absence of steroid-refractory grade 3-4 acute GVHD and chronic GVHD, noted Dr. Dimitrova of the NIH.
All patients, including 19 adults and 10 children (median age, 25 years), received a serotherapy-free, radiation-free, reduced-intensity conditioning regimen designed to optimize immune reconstitution, minimize toxicity and GVHD, reduce the risk of infectious complications, and enable successful use of alternative donors.
The conditioning platform included pentostatin on day –11 and day –7 at 4 mg/m2 along with 8 days of low-dose cyclophosphamide and 2 days of pharmacokinetically dosed busulfan at 4,600 mmol/min. GVHD prophylaxis included posttransplantation cyclophosphamide, mycophenolate mofetil (MMF), and sirolimus.
All patients received T cell–replete bone marrow or peripheral blood stem cell allografts; 72% received alternative donor grafts, Dr. Dimitrova said.
Two patients died, including one with bacterial sepsis and invasive aspergillosis who died on day +44 and one with presumed viral encephalitis who died on day +110. The patients were high risk overall (median HCT–comorbidity index score of 3, with a range of 0-11), and the two who died had HCT-CI scores of 6 and 8, respectively.
An additional accidental death occurred at 18 months after transplant “in the setting of continued remission, good graft function, and no transplant-related complications,” she said.
Neutrophil recovery occurred at a median of 17 days after transplant; three patients experienced graft failure, including one primary failure with autologous recovery on day +14 and two secondary graft failures.
“Two patients with known underlying difficult-to-engraft diseases required second transplants using different nonmyeloabalative platforms, and nevertheless required donor lymphocyte infusions to avoid threatened secondary graft failure,” she said. “The third patient actually had sufficiently improved infectious disease control and has not needed a second transplant to date.”
Overall GVHD incidence using the novel platform has been extremely low, she said, noting that 14% of patients had grade 2-4 GVHD and 3% had grade 3-4 acute GVHD. There was no steroid-refractory GVHD or chronic GVHD.
Among the infectious complications, other than those that led to the two deaths, were cytomegalovirus reactivation in 7 of 16 patients at risk, BK virus–associated hemorrhagic cystitis in 19 of 22 patients at risk, and a suspected case of viral cardiomyopathy that ultimately resolved.
“Importantly, although many patients had Epstein-Barr virus [EBV] control issues prior to transplant, no patients received preemptive EBV-directed therapy, and no patients had EBV-PTLD [posttransplant lymphoproliferative disorder],” she said.
Additionally, blood stream infections were detected in five patients, there were two cases of confirmed aspergillosis, and one child developed cutaneous candidiasis. Other complications and toxicities appeared to relate to underlying pretransplant issues in the affected organ or exuberant immune responses to existing infection.
“Phenotype reversal was evident to some degree in all evaluable patients, even in those with mixed chimerism or unknown underlying genetic defect,” Dr. Dimitrova said.
All 10 patients with malignancy or lymphoproliferative disease as an additional indication for allo-HCT remain in remission, and most patients who required immunoglobulin replacement therapy prior to transplant have been able to discontinue it, she noted.
The findings of this study are of note, because while it has been known for decades that allo-HCT is a potentially curative therapy for patients with PIDs that arise from defects in cells of hematopoietic origin, it frequently fails because of complicating factors or is not an option, Dr. Dimitrova said.
“These patients will often enter transplant with multiple comorbidities and disease sequelae, particularly as diagnosis of PIDs increases in older children and adults following years of illness,” she explained, adding that related donor options may be limited if family members are also affected.
For this reason, and with the goal of improving access to allo-HCT to all who require it, the novel conditioning platform used in this study was developed.
The platform was well tolerated overall, Dr. Dimitrova said, emphasizing the “notably low” GVHD rates.
“Currently we are investigating reduced MMF with the goal of promoting earlier immune reconstitution, and a separate protocol has opened that includes several modifications to this platform aimed at patients with increased risk of graft failure who may not tolerate mixed chimerism early on,” she said, noting that both protocols are currently enrolling.
The meeting was held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
Dr. Dimitrova reported having no financial disclosures.
SOURCE: Dimitrova D et al. TCT 2019, Abstract 54.
HOUSTON – Allogeneic hematopoietic stem cell transplantation (allo-HCT) following a novel reduced-intensity conditioning regimen was largely successful in a heterogeneous cohort of 29 adults and children with primary immunodeficiency in a prospective clinical trial.
At 1 year after transplant, overall survival was 98% and the estimated graft failure–free and graft-versus-host disease (GVHD)–free survival was 82% among the participants, who had various underlying primary immunodeficiencies (PIDs), Dimana Dimitrova, MD, reported at the Transplantation and Cellular Therapy Meetings.
GVHD-free survival was defined in this National Institutes of Health study as the absence of steroid-refractory grade 3-4 acute GVHD and chronic GVHD, noted Dr. Dimitrova of the NIH.
All patients, including 19 adults and 10 children (median age, 25 years), received a serotherapy-free, radiation-free, reduced-intensity conditioning regimen designed to optimize immune reconstitution, minimize toxicity and GVHD, reduce the risk of infectious complications, and enable successful use of alternative donors.
The conditioning platform included pentostatin on day –11 and day –7 at 4 mg/m2 along with 8 days of low-dose cyclophosphamide and 2 days of pharmacokinetically dosed busulfan at 4,600 mmol/min. GVHD prophylaxis included posttransplantation cyclophosphamide, mycophenolate mofetil (MMF), and sirolimus.
All patients received T cell–replete bone marrow or peripheral blood stem cell allografts; 72% received alternative donor grafts, Dr. Dimitrova said.
Two patients died, including one with bacterial sepsis and invasive aspergillosis who died on day +44 and one with presumed viral encephalitis who died on day +110. The patients were high risk overall (median HCT–comorbidity index score of 3, with a range of 0-11), and the two who died had HCT-CI scores of 6 and 8, respectively.
An additional accidental death occurred at 18 months after transplant “in the setting of continued remission, good graft function, and no transplant-related complications,” she said.
Neutrophil recovery occurred at a median of 17 days after transplant; three patients experienced graft failure, including one primary failure with autologous recovery on day +14 and two secondary graft failures.
“Two patients with known underlying difficult-to-engraft diseases required second transplants using different nonmyeloabalative platforms, and nevertheless required donor lymphocyte infusions to avoid threatened secondary graft failure,” she said. “The third patient actually had sufficiently improved infectious disease control and has not needed a second transplant to date.”
Overall GVHD incidence using the novel platform has been extremely low, she said, noting that 14% of patients had grade 2-4 GVHD and 3% had grade 3-4 acute GVHD. There was no steroid-refractory GVHD or chronic GVHD.
Among the infectious complications, other than those that led to the two deaths, were cytomegalovirus reactivation in 7 of 16 patients at risk, BK virus–associated hemorrhagic cystitis in 19 of 22 patients at risk, and a suspected case of viral cardiomyopathy that ultimately resolved.
“Importantly, although many patients had Epstein-Barr virus [EBV] control issues prior to transplant, no patients received preemptive EBV-directed therapy, and no patients had EBV-PTLD [posttransplant lymphoproliferative disorder],” she said.
Additionally, blood stream infections were detected in five patients, there were two cases of confirmed aspergillosis, and one child developed cutaneous candidiasis. Other complications and toxicities appeared to relate to underlying pretransplant issues in the affected organ or exuberant immune responses to existing infection.
“Phenotype reversal was evident to some degree in all evaluable patients, even in those with mixed chimerism or unknown underlying genetic defect,” Dr. Dimitrova said.
All 10 patients with malignancy or lymphoproliferative disease as an additional indication for allo-HCT remain in remission, and most patients who required immunoglobulin replacement therapy prior to transplant have been able to discontinue it, she noted.
The findings of this study are of note, because while it has been known for decades that allo-HCT is a potentially curative therapy for patients with PIDs that arise from defects in cells of hematopoietic origin, it frequently fails because of complicating factors or is not an option, Dr. Dimitrova said.
“These patients will often enter transplant with multiple comorbidities and disease sequelae, particularly as diagnosis of PIDs increases in older children and adults following years of illness,” she explained, adding that related donor options may be limited if family members are also affected.
For this reason, and with the goal of improving access to allo-HCT to all who require it, the novel conditioning platform used in this study was developed.
The platform was well tolerated overall, Dr. Dimitrova said, emphasizing the “notably low” GVHD rates.
“Currently we are investigating reduced MMF with the goal of promoting earlier immune reconstitution, and a separate protocol has opened that includes several modifications to this platform aimed at patients with increased risk of graft failure who may not tolerate mixed chimerism early on,” she said, noting that both protocols are currently enrolling.
The meeting was held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
Dr. Dimitrova reported having no financial disclosures.
SOURCE: Dimitrova D et al. TCT 2019, Abstract 54.
REPORTING FROM TCT 2019
Regimen shows promise as salvage for classical HL
A retrospective study suggests a four-drug regimen can be effective salvage therapy for patients with relapsed or refractory classical Hodgkin lymphoma.
The regimen – brentuximab vedotin plus ifosfamide, gemcitabine, and vinorelbine (BV-IGEV) – produced responses in 27 of 28 patients studied, allowing them to undergo autologous hematopoietic stem cell transplant (HSCT).
After HSCT, the estimated 2-year progression-free survival (PFS) was 87.1% and the overall survival (OS) was 73.5%.
Though this study was limited by its small population and retrospective nature, the results “warrant further investigation,” according to Khadega A. Abuelgasim, MD, of King Abdullah International Medical Research Center in Riyadh, Saudi Arabia, and colleagues.
The researchers reported the results in a letter to Bone Marrow Transplantation.
The study included 28 patients with classical Hodgkin lymphoma, 15 of them male. The patients’ median age at HSCT was 25 years (range, 15-49 years). Twenty patients (71%) had constitutional symptoms at diagnosis, and eight (29%) had bulky disease.
Twenty-three patients (82%) received doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as frontline therapy, and four (14%) received ABVD followed by escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone. One patient received a different frontline regimen.
The median time to relapse was 7.9 months (range, 1.9-133 months), and 12 patients (43%) were refractory to frontline treatment.
Half of patients (n = 14) received BV-IGEV as first salvage. The regimen was given as follows: ifosfamide at 2,000 mg/m2 on days 1-4, gemcitabine at 800 mg/m2 on days 1 and 4, vinorelbine at 20 mg/m2 on day 1, prednisolone at 100 mg on days 1-4, and BV at a dose of 1.8 mg/kg on day 1 of each 3-week IGEV course.
All patients received at least two cycles of BV-IGEV and were assessed for response after one or two cycles. The median follow-up was 17 months (range, 0-65 months).
Twenty patients (71%) had a complete metabolic response to BV-IGEV, seven (25%) had a partial metabolic response, and one patient (4%) had stable disease. The patient with stable disease went on to receive another salvage regimen and achieved a partial response to that regimen.
The most common adverse events during BV-IGEV treatment were grade 3-4 neutropenia (n = 27; 96%) and thrombocytopenia (n = 25; 89%). Febrile neutropenia was also common (n = 16; 57%), as were mucositis (n = 6; 21%) and diarrhea (n = 6; 21%). Six patients had a reduction in BV dose because of an adverse event.
All patients underwent autologous HSCT. They received carmustine, etoposide, cytarabine, and melphalan as conditioning beforehand, and 18 patients (64%) received consolidative BV after transplant.
PFS and OS were calculated from the date of stem cell infusion. The estimated 2-year PFS was 87.1%, and the estimated 2-year OS was 73.5%.
Patients who received BV-IGEV as first salvage fared better than those who received the regimen as second salvage. The PFS rates were 100% and 75%, respectively (P = .0078), and OS rates were 100% and 50%, respectively (P = .08).
Six patients relapsed after HSCT, and three died. Two patients died of progressive disease and one died of pulmonary infection.
These results suggest BV-IGEV can produce high response rates without compromising stem cell mobilization, but the combination should be investigated further, according to the researchers.
The researchers reported having no conflicts of interest.
SOURCE: Abuelgasim KA et al. Bone Marrow Transplant. 2019 Jan 30. doi: 10.1038/s41409-019-0454-z.
A retrospective study suggests a four-drug regimen can be effective salvage therapy for patients with relapsed or refractory classical Hodgkin lymphoma.
The regimen – brentuximab vedotin plus ifosfamide, gemcitabine, and vinorelbine (BV-IGEV) – produced responses in 27 of 28 patients studied, allowing them to undergo autologous hematopoietic stem cell transplant (HSCT).
After HSCT, the estimated 2-year progression-free survival (PFS) was 87.1% and the overall survival (OS) was 73.5%.
Though this study was limited by its small population and retrospective nature, the results “warrant further investigation,” according to Khadega A. Abuelgasim, MD, of King Abdullah International Medical Research Center in Riyadh, Saudi Arabia, and colleagues.
The researchers reported the results in a letter to Bone Marrow Transplantation.
The study included 28 patients with classical Hodgkin lymphoma, 15 of them male. The patients’ median age at HSCT was 25 years (range, 15-49 years). Twenty patients (71%) had constitutional symptoms at diagnosis, and eight (29%) had bulky disease.
Twenty-three patients (82%) received doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as frontline therapy, and four (14%) received ABVD followed by escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone. One patient received a different frontline regimen.
The median time to relapse was 7.9 months (range, 1.9-133 months), and 12 patients (43%) were refractory to frontline treatment.
Half of patients (n = 14) received BV-IGEV as first salvage. The regimen was given as follows: ifosfamide at 2,000 mg/m2 on days 1-4, gemcitabine at 800 mg/m2 on days 1 and 4, vinorelbine at 20 mg/m2 on day 1, prednisolone at 100 mg on days 1-4, and BV at a dose of 1.8 mg/kg on day 1 of each 3-week IGEV course.
All patients received at least two cycles of BV-IGEV and were assessed for response after one or two cycles. The median follow-up was 17 months (range, 0-65 months).
Twenty patients (71%) had a complete metabolic response to BV-IGEV, seven (25%) had a partial metabolic response, and one patient (4%) had stable disease. The patient with stable disease went on to receive another salvage regimen and achieved a partial response to that regimen.
The most common adverse events during BV-IGEV treatment were grade 3-4 neutropenia (n = 27; 96%) and thrombocytopenia (n = 25; 89%). Febrile neutropenia was also common (n = 16; 57%), as were mucositis (n = 6; 21%) and diarrhea (n = 6; 21%). Six patients had a reduction in BV dose because of an adverse event.
All patients underwent autologous HSCT. They received carmustine, etoposide, cytarabine, and melphalan as conditioning beforehand, and 18 patients (64%) received consolidative BV after transplant.
PFS and OS were calculated from the date of stem cell infusion. The estimated 2-year PFS was 87.1%, and the estimated 2-year OS was 73.5%.
Patients who received BV-IGEV as first salvage fared better than those who received the regimen as second salvage. The PFS rates were 100% and 75%, respectively (P = .0078), and OS rates were 100% and 50%, respectively (P = .08).
Six patients relapsed after HSCT, and three died. Two patients died of progressive disease and one died of pulmonary infection.
These results suggest BV-IGEV can produce high response rates without compromising stem cell mobilization, but the combination should be investigated further, according to the researchers.
The researchers reported having no conflicts of interest.
SOURCE: Abuelgasim KA et al. Bone Marrow Transplant. 2019 Jan 30. doi: 10.1038/s41409-019-0454-z.
A retrospective study suggests a four-drug regimen can be effective salvage therapy for patients with relapsed or refractory classical Hodgkin lymphoma.
The regimen – brentuximab vedotin plus ifosfamide, gemcitabine, and vinorelbine (BV-IGEV) – produced responses in 27 of 28 patients studied, allowing them to undergo autologous hematopoietic stem cell transplant (HSCT).
After HSCT, the estimated 2-year progression-free survival (PFS) was 87.1% and the overall survival (OS) was 73.5%.
Though this study was limited by its small population and retrospective nature, the results “warrant further investigation,” according to Khadega A. Abuelgasim, MD, of King Abdullah International Medical Research Center in Riyadh, Saudi Arabia, and colleagues.
The researchers reported the results in a letter to Bone Marrow Transplantation.
The study included 28 patients with classical Hodgkin lymphoma, 15 of them male. The patients’ median age at HSCT was 25 years (range, 15-49 years). Twenty patients (71%) had constitutional symptoms at diagnosis, and eight (29%) had bulky disease.
Twenty-three patients (82%) received doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as frontline therapy, and four (14%) received ABVD followed by escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone. One patient received a different frontline regimen.
The median time to relapse was 7.9 months (range, 1.9-133 months), and 12 patients (43%) were refractory to frontline treatment.
Half of patients (n = 14) received BV-IGEV as first salvage. The regimen was given as follows: ifosfamide at 2,000 mg/m2 on days 1-4, gemcitabine at 800 mg/m2 on days 1 and 4, vinorelbine at 20 mg/m2 on day 1, prednisolone at 100 mg on days 1-4, and BV at a dose of 1.8 mg/kg on day 1 of each 3-week IGEV course.
All patients received at least two cycles of BV-IGEV and were assessed for response after one or two cycles. The median follow-up was 17 months (range, 0-65 months).
Twenty patients (71%) had a complete metabolic response to BV-IGEV, seven (25%) had a partial metabolic response, and one patient (4%) had stable disease. The patient with stable disease went on to receive another salvage regimen and achieved a partial response to that regimen.
The most common adverse events during BV-IGEV treatment were grade 3-4 neutropenia (n = 27; 96%) and thrombocytopenia (n = 25; 89%). Febrile neutropenia was also common (n = 16; 57%), as were mucositis (n = 6; 21%) and diarrhea (n = 6; 21%). Six patients had a reduction in BV dose because of an adverse event.
All patients underwent autologous HSCT. They received carmustine, etoposide, cytarabine, and melphalan as conditioning beforehand, and 18 patients (64%) received consolidative BV after transplant.
PFS and OS were calculated from the date of stem cell infusion. The estimated 2-year PFS was 87.1%, and the estimated 2-year OS was 73.5%.
Patients who received BV-IGEV as first salvage fared better than those who received the regimen as second salvage. The PFS rates were 100% and 75%, respectively (P = .0078), and OS rates were 100% and 50%, respectively (P = .08).
Six patients relapsed after HSCT, and three died. Two patients died of progressive disease and one died of pulmonary infection.
These results suggest BV-IGEV can produce high response rates without compromising stem cell mobilization, but the combination should be investigated further, according to the researchers.
The researchers reported having no conflicts of interest.
SOURCE: Abuelgasim KA et al. Bone Marrow Transplant. 2019 Jan 30. doi: 10.1038/s41409-019-0454-z.
FROM BONE MARROW TRANSPLANTATION
FDA aims to boost safety of platelets for transfusion
The Food and Drug Administration is asking for comments on its
The draft document, “Bacterial Risk Control Strategies for Blood Collection Establishments and Transfusion Services to Enhance the Safety and Availability of Platelets for Transfusion,” will be open for public comment through Feb. 4, 2019.
It is the first update to the policy document since 2016.
In the draft guidance, the FDA recommended three strategies for platelets stored for 5 days from collection. For apheresis platelets and prestorage pools, the FDA suggested an initial primary culture followed by a secondary culture on day 3 or day 4 or an initial primary culture followed by secondary testing with a rapid test. The third strategy – for apheresis platelets – is pathogen reduction alone.
The FDA also outlined three strategies for testing platelets stored for 7 days, all of which apply to apheresis platelets. The methods include an initial primary culture followed by a secondary culture no earlier than day 4, using a device labeled as a safety measure; an initial primary culture followed by a secondary rapid test, labeled as a safety measure; or large volume delayed sampling.
The supply of blood and blood components in the United States is among the safest in the world, FDA Commissioner Scott Gottlieb, MD, said in a statement. The FDA’s continuously updated protocols are intended to keep it that way.
“Blood and blood components are some of the most critical medical products American patients depend upon,” Dr. Gottlieb wrote. “But there remains risk, albeit uncommon, of contamination with infectious diseases, particularly with blood products that are stored at room temperature. While we’ve made great strides in reducing the risk of blood contamination through donor screening and laboratory testing, we continue to support innovations and blood product alternatives that can better keep pace with emerging pathogens and reduce some of the logistical challenges and costs associated with ensuring the safety of blood products.”
Since the 2016 guidance document was issued, new strategies for bacterial detection have become available that could potentially reduce the risk of contamination of platelets and permit extension of platelet dating up to 7 days, including bacterial testing strategies using culture-based devices, rapid bacterial detection devices, and the implementation of pathogen reduction technology.
The recommendations in the draft guidance incorporate ideas put forth during a July 2018 meeting of the agency’s Blood Products Advisory Committee. Committee members were asked to discuss the advantages and disadvantages of various strategies to control the risk of bacterial contamination in platelets, including the scientific evidence and the operational considerations involved. Their comments have been incorporated into the new draft guidance document.
In late November 2018, the FDA held a public workshop to encourage a scientific discussion on a range of pathogen reduction topics, including the development of novel technologies. “The ideal pathogen reduction technology would: be relatively inexpensive, be simple to implement on whole blood, allow treated blood to subsequently be separated into components or alternatively could be performed on apheresis products, inactivate a broad range of pathogens, and would have no adverse effect on product safety or product yield,” the FDA noted in a statement.
The Food and Drug Administration is asking for comments on its
The draft document, “Bacterial Risk Control Strategies for Blood Collection Establishments and Transfusion Services to Enhance the Safety and Availability of Platelets for Transfusion,” will be open for public comment through Feb. 4, 2019.
It is the first update to the policy document since 2016.
In the draft guidance, the FDA recommended three strategies for platelets stored for 5 days from collection. For apheresis platelets and prestorage pools, the FDA suggested an initial primary culture followed by a secondary culture on day 3 or day 4 or an initial primary culture followed by secondary testing with a rapid test. The third strategy – for apheresis platelets – is pathogen reduction alone.
The FDA also outlined three strategies for testing platelets stored for 7 days, all of which apply to apheresis platelets. The methods include an initial primary culture followed by a secondary culture no earlier than day 4, using a device labeled as a safety measure; an initial primary culture followed by a secondary rapid test, labeled as a safety measure; or large volume delayed sampling.
The supply of blood and blood components in the United States is among the safest in the world, FDA Commissioner Scott Gottlieb, MD, said in a statement. The FDA’s continuously updated protocols are intended to keep it that way.
“Blood and blood components are some of the most critical medical products American patients depend upon,” Dr. Gottlieb wrote. “But there remains risk, albeit uncommon, of contamination with infectious diseases, particularly with blood products that are stored at room temperature. While we’ve made great strides in reducing the risk of blood contamination through donor screening and laboratory testing, we continue to support innovations and blood product alternatives that can better keep pace with emerging pathogens and reduce some of the logistical challenges and costs associated with ensuring the safety of blood products.”
Since the 2016 guidance document was issued, new strategies for bacterial detection have become available that could potentially reduce the risk of contamination of platelets and permit extension of platelet dating up to 7 days, including bacterial testing strategies using culture-based devices, rapid bacterial detection devices, and the implementation of pathogen reduction technology.
The recommendations in the draft guidance incorporate ideas put forth during a July 2018 meeting of the agency’s Blood Products Advisory Committee. Committee members were asked to discuss the advantages and disadvantages of various strategies to control the risk of bacterial contamination in platelets, including the scientific evidence and the operational considerations involved. Their comments have been incorporated into the new draft guidance document.
In late November 2018, the FDA held a public workshop to encourage a scientific discussion on a range of pathogen reduction topics, including the development of novel technologies. “The ideal pathogen reduction technology would: be relatively inexpensive, be simple to implement on whole blood, allow treated blood to subsequently be separated into components or alternatively could be performed on apheresis products, inactivate a broad range of pathogens, and would have no adverse effect on product safety or product yield,” the FDA noted in a statement.
The Food and Drug Administration is asking for comments on its
The draft document, “Bacterial Risk Control Strategies for Blood Collection Establishments and Transfusion Services to Enhance the Safety and Availability of Platelets for Transfusion,” will be open for public comment through Feb. 4, 2019.
It is the first update to the policy document since 2016.
In the draft guidance, the FDA recommended three strategies for platelets stored for 5 days from collection. For apheresis platelets and prestorage pools, the FDA suggested an initial primary culture followed by a secondary culture on day 3 or day 4 or an initial primary culture followed by secondary testing with a rapid test. The third strategy – for apheresis platelets – is pathogen reduction alone.
The FDA also outlined three strategies for testing platelets stored for 7 days, all of which apply to apheresis platelets. The methods include an initial primary culture followed by a secondary culture no earlier than day 4, using a device labeled as a safety measure; an initial primary culture followed by a secondary rapid test, labeled as a safety measure; or large volume delayed sampling.
The supply of blood and blood components in the United States is among the safest in the world, FDA Commissioner Scott Gottlieb, MD, said in a statement. The FDA’s continuously updated protocols are intended to keep it that way.
“Blood and blood components are some of the most critical medical products American patients depend upon,” Dr. Gottlieb wrote. “But there remains risk, albeit uncommon, of contamination with infectious diseases, particularly with blood products that are stored at room temperature. While we’ve made great strides in reducing the risk of blood contamination through donor screening and laboratory testing, we continue to support innovations and blood product alternatives that can better keep pace with emerging pathogens and reduce some of the logistical challenges and costs associated with ensuring the safety of blood products.”
Since the 2016 guidance document was issued, new strategies for bacterial detection have become available that could potentially reduce the risk of contamination of platelets and permit extension of platelet dating up to 7 days, including bacterial testing strategies using culture-based devices, rapid bacterial detection devices, and the implementation of pathogen reduction technology.
The recommendations in the draft guidance incorporate ideas put forth during a July 2018 meeting of the agency’s Blood Products Advisory Committee. Committee members were asked to discuss the advantages and disadvantages of various strategies to control the risk of bacterial contamination in platelets, including the scientific evidence and the operational considerations involved. Their comments have been incorporated into the new draft guidance document.
In late November 2018, the FDA held a public workshop to encourage a scientific discussion on a range of pathogen reduction topics, including the development of novel technologies. “The ideal pathogen reduction technology would: be relatively inexpensive, be simple to implement on whole blood, allow treated blood to subsequently be separated into components or alternatively could be performed on apheresis products, inactivate a broad range of pathogens, and would have no adverse effect on product safety or product yield,” the FDA noted in a statement.
In-hospital blood saving strategy appears safe with anemia
A blood management initiative that reduced RBC transfusions in the hospital did not adversely impact long-term outcomes after discharge, a retrospective analysis of an extensive patient database suggested.
Tolerating moderate in-hospital anemia did not increase subsequent RBC use, readmission, or mortality over the next 6 months, according to results of the study, which drew on nearly half a million patient records.
In fact, modest mortality decreases were seen over time for patients with moderate anemia, perhaps because of concomitant initiatives that targeted infectious and circulatory conditions, reported Nareg H. Roubinian, MD, of Kaiser Permanente Northern California in Oakland and the University of California, San Francisco, and coinvestigators.
“These data support the efficacy and safety of practice recommendations to limit red blood cell transfusion in patients with anemia during and after hospitalization,” Dr. Roubinian and colleagues wrote in their report, which appears in the Annals of Internal Medicine.
However, additional studies are needed to guide anemia management, they wrote, particularly since persistent anemia has impacts on quality of life that are “likely substantial” and linked to the severity of that anemia.
Dr. Roubinian and colleagues sought to evaluate the impact of blood management programs – initiated starting in 2010 – that included blood-sparing surgical and medical techniques, increased use of hemostatic and cell salvage agents, and treatment of suboptimal iron stores before surgery.
In previous retrospective cohort studies, the researchers had found that the blood conservation strategies did not impact in-hospital or 30-day mortality rates, which was consistent with short-term safety data from clinical trials and other observational studies.
Their latest report on longer-term outcomes was based on data from Kaiser Permanente Northern California for 445,371 adults who had 801,261 hospitalizations with discharges between 2010 and 2014. In this cohort, moderate anemia (hemoglobin between 7 g/dL and 10 g/dL) at discharge occurred in 119,489 patients (27%) and 187,440 hospitalizations overall (23%).
Over the 2010-2014 period, RBC transfusions decreased by more than 25% in the inpatient and outpatient settings; and in parallel, the prevalence of moderate anemia at hospital discharge increased from 20% to 25%.
However, the risks of subsequent RBC transfusions and rehospitalization after discharge with anemia decreased during the study period, and mortality rates stayed steady or decreased slightly.
Among patients with moderate anemia, the proportion with subsequent RBC transfusions within 6 months decreased from 18.9% in 2010 to 16.8% in 2014 (P less than .001), while the rate of rehospitalization within 6 months decreased from 36.5% to 32.8% over that same time period (P less than .001).
The adjusted 6-month mortality rate likewise decreased from 16.1% to 15.6% (P = .004) over that time period among patients with moderate anemia.
The study was supported by a grant from the National Heart, Lung, and Blood Institute. Dr. Roubinian and several coauthors reported grants during the conduct of the study from the National Institutes of Health.
SOURCE: Roubinian NH et al. Ann Intern Med. 2018 Dec 18. doi: 10.7326/M17-3253.
Some scrutiny is warranted of the observation of Roubinian et al. that long-term transfusion, readmission, and mortality outcomes were apparently unaffected by decreased in-hospital RBC transfusions, according to the authors of an accompanying editorial.
“Missing here is a wide spectrum of morbidity outcomes and issues related to diminished quality of life that do not reach the level of severity that would necessitate admission but nonetheless detract from patients’ health and well-being,” wrote Aryeh Shander, MD, and Lawrence Tim Goodnough, MD.
Moreover, transfusion rate is not a clinical outcome, they noted, adding that readmission and mortality are important outcomes but that they do not accurately or fully reflect patient well-being.
While blood management initiatives may be a safe practice, as Roubinian et al. found, proper management of anemia after discharge may actually improve outcomes, given the many consequences of anemia.
Instead of again testing whether restricting transfusions is acceptable because of lack of impact on outcomes, future studies could evaluate a “more sensible” hypothesis that proper anemia management – especially post discharge – could improve outcomes.
“Let’s increase efforts to prevent and treat anemia properly, rather than requiring patients to tolerate it,” they wrote.
Dr. Shander is with Englewood (N.J.) Hospital and Medical Center; Dr. Goodnough is with Stanford (Calif.) University. Dr. Shander reported consulting fees from Vifor and AMAG. Dr. Goodnough reported having no relevant financial disclosures. Their comments are taken from an accompanying editorial (Ann Intern Med. 2018 Dec 18. doi: 10.7326/M18-3145).
Some scrutiny is warranted of the observation of Roubinian et al. that long-term transfusion, readmission, and mortality outcomes were apparently unaffected by decreased in-hospital RBC transfusions, according to the authors of an accompanying editorial.
“Missing here is a wide spectrum of morbidity outcomes and issues related to diminished quality of life that do not reach the level of severity that would necessitate admission but nonetheless detract from patients’ health and well-being,” wrote Aryeh Shander, MD, and Lawrence Tim Goodnough, MD.
Moreover, transfusion rate is not a clinical outcome, they noted, adding that readmission and mortality are important outcomes but that they do not accurately or fully reflect patient well-being.
While blood management initiatives may be a safe practice, as Roubinian et al. found, proper management of anemia after discharge may actually improve outcomes, given the many consequences of anemia.
Instead of again testing whether restricting transfusions is acceptable because of lack of impact on outcomes, future studies could evaluate a “more sensible” hypothesis that proper anemia management – especially post discharge – could improve outcomes.
“Let’s increase efforts to prevent and treat anemia properly, rather than requiring patients to tolerate it,” they wrote.
Dr. Shander is with Englewood (N.J.) Hospital and Medical Center; Dr. Goodnough is with Stanford (Calif.) University. Dr. Shander reported consulting fees from Vifor and AMAG. Dr. Goodnough reported having no relevant financial disclosures. Their comments are taken from an accompanying editorial (Ann Intern Med. 2018 Dec 18. doi: 10.7326/M18-3145).
Some scrutiny is warranted of the observation of Roubinian et al. that long-term transfusion, readmission, and mortality outcomes were apparently unaffected by decreased in-hospital RBC transfusions, according to the authors of an accompanying editorial.
“Missing here is a wide spectrum of morbidity outcomes and issues related to diminished quality of life that do not reach the level of severity that would necessitate admission but nonetheless detract from patients’ health and well-being,” wrote Aryeh Shander, MD, and Lawrence Tim Goodnough, MD.
Moreover, transfusion rate is not a clinical outcome, they noted, adding that readmission and mortality are important outcomes but that they do not accurately or fully reflect patient well-being.
While blood management initiatives may be a safe practice, as Roubinian et al. found, proper management of anemia after discharge may actually improve outcomes, given the many consequences of anemia.
Instead of again testing whether restricting transfusions is acceptable because of lack of impact on outcomes, future studies could evaluate a “more sensible” hypothesis that proper anemia management – especially post discharge – could improve outcomes.
“Let’s increase efforts to prevent and treat anemia properly, rather than requiring patients to tolerate it,” they wrote.
Dr. Shander is with Englewood (N.J.) Hospital and Medical Center; Dr. Goodnough is with Stanford (Calif.) University. Dr. Shander reported consulting fees from Vifor and AMAG. Dr. Goodnough reported having no relevant financial disclosures. Their comments are taken from an accompanying editorial (Ann Intern Med. 2018 Dec 18. doi: 10.7326/M18-3145).
A blood management initiative that reduced RBC transfusions in the hospital did not adversely impact long-term outcomes after discharge, a retrospective analysis of an extensive patient database suggested.
Tolerating moderate in-hospital anemia did not increase subsequent RBC use, readmission, or mortality over the next 6 months, according to results of the study, which drew on nearly half a million patient records.
In fact, modest mortality decreases were seen over time for patients with moderate anemia, perhaps because of concomitant initiatives that targeted infectious and circulatory conditions, reported Nareg H. Roubinian, MD, of Kaiser Permanente Northern California in Oakland and the University of California, San Francisco, and coinvestigators.
“These data support the efficacy and safety of practice recommendations to limit red blood cell transfusion in patients with anemia during and after hospitalization,” Dr. Roubinian and colleagues wrote in their report, which appears in the Annals of Internal Medicine.
However, additional studies are needed to guide anemia management, they wrote, particularly since persistent anemia has impacts on quality of life that are “likely substantial” and linked to the severity of that anemia.
Dr. Roubinian and colleagues sought to evaluate the impact of blood management programs – initiated starting in 2010 – that included blood-sparing surgical and medical techniques, increased use of hemostatic and cell salvage agents, and treatment of suboptimal iron stores before surgery.
In previous retrospective cohort studies, the researchers had found that the blood conservation strategies did not impact in-hospital or 30-day mortality rates, which was consistent with short-term safety data from clinical trials and other observational studies.
Their latest report on longer-term outcomes was based on data from Kaiser Permanente Northern California for 445,371 adults who had 801,261 hospitalizations with discharges between 2010 and 2014. In this cohort, moderate anemia (hemoglobin between 7 g/dL and 10 g/dL) at discharge occurred in 119,489 patients (27%) and 187,440 hospitalizations overall (23%).
Over the 2010-2014 period, RBC transfusions decreased by more than 25% in the inpatient and outpatient settings; and in parallel, the prevalence of moderate anemia at hospital discharge increased from 20% to 25%.
However, the risks of subsequent RBC transfusions and rehospitalization after discharge with anemia decreased during the study period, and mortality rates stayed steady or decreased slightly.
Among patients with moderate anemia, the proportion with subsequent RBC transfusions within 6 months decreased from 18.9% in 2010 to 16.8% in 2014 (P less than .001), while the rate of rehospitalization within 6 months decreased from 36.5% to 32.8% over that same time period (P less than .001).
The adjusted 6-month mortality rate likewise decreased from 16.1% to 15.6% (P = .004) over that time period among patients with moderate anemia.
The study was supported by a grant from the National Heart, Lung, and Blood Institute. Dr. Roubinian and several coauthors reported grants during the conduct of the study from the National Institutes of Health.
SOURCE: Roubinian NH et al. Ann Intern Med. 2018 Dec 18. doi: 10.7326/M17-3253.
A blood management initiative that reduced RBC transfusions in the hospital did not adversely impact long-term outcomes after discharge, a retrospective analysis of an extensive patient database suggested.
Tolerating moderate in-hospital anemia did not increase subsequent RBC use, readmission, or mortality over the next 6 months, according to results of the study, which drew on nearly half a million patient records.
In fact, modest mortality decreases were seen over time for patients with moderate anemia, perhaps because of concomitant initiatives that targeted infectious and circulatory conditions, reported Nareg H. Roubinian, MD, of Kaiser Permanente Northern California in Oakland and the University of California, San Francisco, and coinvestigators.
“These data support the efficacy and safety of practice recommendations to limit red blood cell transfusion in patients with anemia during and after hospitalization,” Dr. Roubinian and colleagues wrote in their report, which appears in the Annals of Internal Medicine.
However, additional studies are needed to guide anemia management, they wrote, particularly since persistent anemia has impacts on quality of life that are “likely substantial” and linked to the severity of that anemia.
Dr. Roubinian and colleagues sought to evaluate the impact of blood management programs – initiated starting in 2010 – that included blood-sparing surgical and medical techniques, increased use of hemostatic and cell salvage agents, and treatment of suboptimal iron stores before surgery.
In previous retrospective cohort studies, the researchers had found that the blood conservation strategies did not impact in-hospital or 30-day mortality rates, which was consistent with short-term safety data from clinical trials and other observational studies.
Their latest report on longer-term outcomes was based on data from Kaiser Permanente Northern California for 445,371 adults who had 801,261 hospitalizations with discharges between 2010 and 2014. In this cohort, moderate anemia (hemoglobin between 7 g/dL and 10 g/dL) at discharge occurred in 119,489 patients (27%) and 187,440 hospitalizations overall (23%).
Over the 2010-2014 period, RBC transfusions decreased by more than 25% in the inpatient and outpatient settings; and in parallel, the prevalence of moderate anemia at hospital discharge increased from 20% to 25%.
However, the risks of subsequent RBC transfusions and rehospitalization after discharge with anemia decreased during the study period, and mortality rates stayed steady or decreased slightly.
Among patients with moderate anemia, the proportion with subsequent RBC transfusions within 6 months decreased from 18.9% in 2010 to 16.8% in 2014 (P less than .001), while the rate of rehospitalization within 6 months decreased from 36.5% to 32.8% over that same time period (P less than .001).
The adjusted 6-month mortality rate likewise decreased from 16.1% to 15.6% (P = .004) over that time period among patients with moderate anemia.
The study was supported by a grant from the National Heart, Lung, and Blood Institute. Dr. Roubinian and several coauthors reported grants during the conduct of the study from the National Institutes of Health.
SOURCE: Roubinian NH et al. Ann Intern Med. 2018 Dec 18. doi: 10.7326/M17-3253.
FROM THE ANNALS OF INTERNAL MEDICINE
Key clinical point:
Major finding: The adjusted 6-month mortality rate decreased from 16.1% to 15.6% (P = .004) in the 4-year period following implementation of blood conservation strategies.
Study details: A retrospective cohort study including 445,371 adults hospitalized and discharged between 2010 and 2014.
Disclosures: The study was supported by a grant from the National Heart, Lung, and Blood Institute. Several authors reported grants during the conduct of the study from the National Institutes of Health.
Source: Roubinian NH et al. Ann Intern Med. 2018 Dec 18. doi: 10.7326/M17-3253.
Preop anemia management saves blood, costs
BOSTON – A pilot anemia optimization program resulted in significant increases in day-of-surgery hemoglobin levels and reductions in RBC transfusion rates and costs in one center, but whether patient outcomes also improved is still not known.
By diagnosing anemia at the preanesthesia visit and providing anemic patients with dietary guidance and supplementation prior to cardiac surgery, blood program managers noticed a more than $360 reduction in per-patient blood-product acquisition costs, a more than $1,800 average reduction per patient in transfusion costs, and overall cost savings of more than $100,000 over 18 months, compared with historical data.
The findings were reported by Christine M. Cahill, RN, from Strong Memorial Hospital in Rochester, N.Y., and the University of Rochester (N.Y.), at AABB 2018, the annual meeting of the group formerly known as the American Association of Blood Banks.
“Anemia has been thought of as a relatively benign thing our patients live with traditionally, but what we have been finding lately is that anemia is actually more serious than we once thought, and is an independent risk factor for hospitalization, readmission, increased patient length of stay, loss of function, and diminished quality of life,” she said.
Anemia also increases the likelihood that a patient will require allogeneic transfusions and is an independent risk factor for morbidity and mortality, she added.
The pilot program, which ran from February 2016 to September 2017, was designed to test the feasibility of diagnosing anemia during a cardiology consult visit and implementing a management plan.
During the study period, 240 patients presenting for elective cardiac surgery were screened for anemia, and 58 were diagnosed as anemic, defined as a hemoglobin level of less than 12 g/dL. These patients were referred for anemia work-ups, which found that 33 patients had iron-deficient anemia and 25 had anemia from other causes. Controls were patients who underwent cardiac surgery from March to July 2015, matched by age, sex, and procedures.
Treatments for iron-deficient patients included oral iron (7 patients), intravenous iron with or without folate (20 patients), or oral folate with or without vitamin B12 (5 patients). One iron-deficient patient could not have surgery delayed for anemia management.
Of the iron-replete patients, one received oral iron and 17 received folate plus or minus vitamin B12. The remaining seven iron-replete patients were not treated for anemia.
One iron-deficient patient had a reaction to the infusion and did not receive a scheduled second dose due to the need for immediate surgery. A second patient scheduled for intravenous iron and folate broke an arm and therefore missed an intravenous infusion appointment. No other complications or reactions occurred.
Intraoperative transfusion units used in the anemia management group totaled 10, compared with 68 for controls. Postoperative transfusion units used were also significantly lower following anemia management at 13 versus 122, respectively.
The rate of RBC transfusions among patients with anemia management was 24%, compared with 60% for controls (P less than .0001). Patients in the management program also had significantly higher day-of-surgery hemoglobin, at 11.01 g/dL versus 10.16 g/dL (P less than .001), and less RBC utilization, at an average 0.40 units per patient versus 2.07 for controls (P less than .0001).
The average per patient savings in acquisition costs was $367.40, the average transfusion cost saving was $1,837, and the total cost savings over the life of the pilot program was $106,546.
The keys to success for similar programs is “to make sure you do your homework,” Ms. Cahill said. Specifically, she recommended feasibility studies, evaluation of the potential impact of infusions on the service, work flow analyses, and cost analyses. It’s also important to get high-level administrative support as well as buy-in from surgeons and patients.
Future studies should include assessment of patient outcomes, safety, and length of ICU and hospital stay, she emphasized.
The study was internally funded. Ms. Cahill reported having no conflicts of interest.
SOURCE: Cahill CM et al. AABB 2018, Abstract PBM4-ST4-22.
BOSTON – A pilot anemia optimization program resulted in significant increases in day-of-surgery hemoglobin levels and reductions in RBC transfusion rates and costs in one center, but whether patient outcomes also improved is still not known.
By diagnosing anemia at the preanesthesia visit and providing anemic patients with dietary guidance and supplementation prior to cardiac surgery, blood program managers noticed a more than $360 reduction in per-patient blood-product acquisition costs, a more than $1,800 average reduction per patient in transfusion costs, and overall cost savings of more than $100,000 over 18 months, compared with historical data.
The findings were reported by Christine M. Cahill, RN, from Strong Memorial Hospital in Rochester, N.Y., and the University of Rochester (N.Y.), at AABB 2018, the annual meeting of the group formerly known as the American Association of Blood Banks.
“Anemia has been thought of as a relatively benign thing our patients live with traditionally, but what we have been finding lately is that anemia is actually more serious than we once thought, and is an independent risk factor for hospitalization, readmission, increased patient length of stay, loss of function, and diminished quality of life,” she said.
Anemia also increases the likelihood that a patient will require allogeneic transfusions and is an independent risk factor for morbidity and mortality, she added.
The pilot program, which ran from February 2016 to September 2017, was designed to test the feasibility of diagnosing anemia during a cardiology consult visit and implementing a management plan.
During the study period, 240 patients presenting for elective cardiac surgery were screened for anemia, and 58 were diagnosed as anemic, defined as a hemoglobin level of less than 12 g/dL. These patients were referred for anemia work-ups, which found that 33 patients had iron-deficient anemia and 25 had anemia from other causes. Controls were patients who underwent cardiac surgery from March to July 2015, matched by age, sex, and procedures.
Treatments for iron-deficient patients included oral iron (7 patients), intravenous iron with or without folate (20 patients), or oral folate with or without vitamin B12 (5 patients). One iron-deficient patient could not have surgery delayed for anemia management.
Of the iron-replete patients, one received oral iron and 17 received folate plus or minus vitamin B12. The remaining seven iron-replete patients were not treated for anemia.
One iron-deficient patient had a reaction to the infusion and did not receive a scheduled second dose due to the need for immediate surgery. A second patient scheduled for intravenous iron and folate broke an arm and therefore missed an intravenous infusion appointment. No other complications or reactions occurred.
Intraoperative transfusion units used in the anemia management group totaled 10, compared with 68 for controls. Postoperative transfusion units used were also significantly lower following anemia management at 13 versus 122, respectively.
The rate of RBC transfusions among patients with anemia management was 24%, compared with 60% for controls (P less than .0001). Patients in the management program also had significantly higher day-of-surgery hemoglobin, at 11.01 g/dL versus 10.16 g/dL (P less than .001), and less RBC utilization, at an average 0.40 units per patient versus 2.07 for controls (P less than .0001).
The average per patient savings in acquisition costs was $367.40, the average transfusion cost saving was $1,837, and the total cost savings over the life of the pilot program was $106,546.
The keys to success for similar programs is “to make sure you do your homework,” Ms. Cahill said. Specifically, she recommended feasibility studies, evaluation of the potential impact of infusions on the service, work flow analyses, and cost analyses. It’s also important to get high-level administrative support as well as buy-in from surgeons and patients.
Future studies should include assessment of patient outcomes, safety, and length of ICU and hospital stay, she emphasized.
The study was internally funded. Ms. Cahill reported having no conflicts of interest.
SOURCE: Cahill CM et al. AABB 2018, Abstract PBM4-ST4-22.
BOSTON – A pilot anemia optimization program resulted in significant increases in day-of-surgery hemoglobin levels and reductions in RBC transfusion rates and costs in one center, but whether patient outcomes also improved is still not known.
By diagnosing anemia at the preanesthesia visit and providing anemic patients with dietary guidance and supplementation prior to cardiac surgery, blood program managers noticed a more than $360 reduction in per-patient blood-product acquisition costs, a more than $1,800 average reduction per patient in transfusion costs, and overall cost savings of more than $100,000 over 18 months, compared with historical data.
The findings were reported by Christine M. Cahill, RN, from Strong Memorial Hospital in Rochester, N.Y., and the University of Rochester (N.Y.), at AABB 2018, the annual meeting of the group formerly known as the American Association of Blood Banks.
“Anemia has been thought of as a relatively benign thing our patients live with traditionally, but what we have been finding lately is that anemia is actually more serious than we once thought, and is an independent risk factor for hospitalization, readmission, increased patient length of stay, loss of function, and diminished quality of life,” she said.
Anemia also increases the likelihood that a patient will require allogeneic transfusions and is an independent risk factor for morbidity and mortality, she added.
The pilot program, which ran from February 2016 to September 2017, was designed to test the feasibility of diagnosing anemia during a cardiology consult visit and implementing a management plan.
During the study period, 240 patients presenting for elective cardiac surgery were screened for anemia, and 58 were diagnosed as anemic, defined as a hemoglobin level of less than 12 g/dL. These patients were referred for anemia work-ups, which found that 33 patients had iron-deficient anemia and 25 had anemia from other causes. Controls were patients who underwent cardiac surgery from March to July 2015, matched by age, sex, and procedures.
Treatments for iron-deficient patients included oral iron (7 patients), intravenous iron with or without folate (20 patients), or oral folate with or without vitamin B12 (5 patients). One iron-deficient patient could not have surgery delayed for anemia management.
Of the iron-replete patients, one received oral iron and 17 received folate plus or minus vitamin B12. The remaining seven iron-replete patients were not treated for anemia.
One iron-deficient patient had a reaction to the infusion and did not receive a scheduled second dose due to the need for immediate surgery. A second patient scheduled for intravenous iron and folate broke an arm and therefore missed an intravenous infusion appointment. No other complications or reactions occurred.
Intraoperative transfusion units used in the anemia management group totaled 10, compared with 68 for controls. Postoperative transfusion units used were also significantly lower following anemia management at 13 versus 122, respectively.
The rate of RBC transfusions among patients with anemia management was 24%, compared with 60% for controls (P less than .0001). Patients in the management program also had significantly higher day-of-surgery hemoglobin, at 11.01 g/dL versus 10.16 g/dL (P less than .001), and less RBC utilization, at an average 0.40 units per patient versus 2.07 for controls (P less than .0001).
The average per patient savings in acquisition costs was $367.40, the average transfusion cost saving was $1,837, and the total cost savings over the life of the pilot program was $106,546.
The keys to success for similar programs is “to make sure you do your homework,” Ms. Cahill said. Specifically, she recommended feasibility studies, evaluation of the potential impact of infusions on the service, work flow analyses, and cost analyses. It’s also important to get high-level administrative support as well as buy-in from surgeons and patients.
Future studies should include assessment of patient outcomes, safety, and length of ICU and hospital stay, she emphasized.
The study was internally funded. Ms. Cahill reported having no conflicts of interest.
SOURCE: Cahill CM et al. AABB 2018, Abstract PBM4-ST4-22.
REPORTING FROM AABB 2018
Key clinical point:
Major finding: The total cost savings over the life of a pilot anemia management program was $106,546.
Study details: A case-control study with 58 patients scheduled for elective cardiac surgery and matched historical controls.
Disclosures: The study was internally funded. Ms. Cahill reported having no conflicts of interest.
Source: Cahill CM et al. AABB 2018, Abstract PBM4-ST4-22.