Anemia

ORLANDO – Stored red blood cells kept for longer than a few weeks do not impair outcomes or harm the patients who receive them, Dr. Christine Cserti-Gazdewich reported at the annual meeting of the American Society of Hematology.

In a randomized clinical trial conducted in Kanpala, Uganda, where severe anemia with lactic acidosis is common, children who received RBCs that had been stored from 25-35 days had outcomes that were not inferior to those of children who received RBCs delivered within 10 days of collection. The findings have significant, positive implications for countries and geographic regions where there are chronic shortages of blood products, said Dr. Cserti-Gazdewich, of Toronto General Hospital.

ORLANDO – Stored red blood cells kept for longer than a few weeks do not impair outcomes or harm the patients who receive them, Dr. Christine Cserti-Gazdewich reported at the annual meeting of the American Society of Hematology.

In a randomized clinical trial conducted in Kanpala, Uganda, where severe anemia with lactic acidosis is common, children who received RBCs that had been stored from 25-35 days had outcomes that were not inferior to those of children who received RBCs delivered within 10 days of collection. The findings have significant, positive implications for countries and geographic regions where there are chronic shortages of blood products, said Dr. Cserti-Gazdewich, of Toronto General Hospital.

ORLANDO – Stored red blood cells kept for longer than a few weeks do not impair outcomes or harm the patients who receive them, Dr. Christine Cserti-Gazdewich reported at the annual meeting of the American Society of Hematology.

In a randomized clinical trial conducted in Kanpala, Uganda, where severe anemia with lactic acidosis is common, children who received RBCs that had been stored from 25-35 days had outcomes that were not inferior to those of children who received RBCs delivered within 10 days of collection. The findings have significant, positive implications for countries and geographic regions where there are chronic shortages of blood products, said Dr. Cserti-Gazdewich, of Toronto General Hospital.

ORLANDO – Oral hydroxyurea is as good as chronic red blood cell transfusions for prevention of primary stroke in children at high-risk for this devastating complication of sickle cell disease, results of the TWiTCH study show.

No child suffered a stroke with either hydroxyurea or monthly transfusions and transcranial doppler (TCD) velocities were maintained in both arms.

The study was stopped early, however, after noninferiority was shown for the primary end point of TCD mean velocities on the index side at 24 months, with a post-hoc analysis suggesting hydroxyurea may even be superior, study author Dr. Russell E. Ware, director of hematology at Cincinnati (Ohio) Children’s Hospital Medical Center, reported during the plenary session at the annual meeting of the American Society of Hematology.

Patrice Wendling/Frontline Medical News

“Hydroxyurea therapy can substitute for chronic transfusions to maintain TCD velocities and help prevent primary stroke,” he said during a press briefing.

The final mean TCD velocities were 143 cm/second in the transfusion arm and 138 cm/sec in the hydroxyurea arm, resulting in P values of 8.82 x 10^-16 for non-inferiority by intention-to-treat analysis and 0.023 for superiority in a post-hoc analysis.

Hydroxyurea also had the added benefit of improving iron overload status more than monthly transfusions based on a greater average change in serum ferritin (-1,085 ng/mL vs. -38 ng/mL; P less than .001) and liver iron concentrations (-1.9 mg/g vs. +2.4 mg/g; P = .001), according to their report.

Press briefing moderator Dr. Alexis Thompson, of the Ann & Robert H. Lurie Children’s Hospital of Chicago, commented, “This truly is one of the abstracts that are being presenting at the meeting today that can be defined as practice changing. There are many families who have great difficulty accepting the reality, prior to the TWiTCH study, of their children having to be transfused lifelong.”

Strokes occur in up to 10% of children with sickle cell disease (SCD). Transfusions are effective for stroke prophylaxis in this setting, but have to be continued lifelong and can lead to iron overload and other complications.

Based on the participating sites, at least 80% of children with abnormal TCD velocities currently on blood transfusions to prevent stroke would be eligible for treatment with hydroxyurea, Dr. Ware said.

Hydroxyurea increases the amount of fetal hemoglobin and fetal red blood cells and was approved more than a decade ago to ameliorate the acute and chronic complications of SCD. Its use could provide dramatic cost savings for families since a transfusion costs about $1,000 to $2,000 every month, whereas hydroxyurea costs less than a dollar a day, Dr. Ware said in an interview.

TWiTCH (TCD with Transfusions Changing to Hydroxyurea) was conducted at 26 pediatric programs and used TCD to identify 121 children with SCD who were at elevated risk of stroke based on abnormally high cerebral artery flow velocities of at least 200 cm/sec. The children were evenly randomized to 24 months of treatment. TCD velocities were obtained every 12 weeks and reviewed centrally, with local investigators blinded to the results. All children had received transfusions for at least 12 months, but had not developed severe vasculopathy.

The transfusion arm was maintained at a target hemoglobin S level of less than 30% and chelation used to manage elevated liver concentrations. Transfusions were allowed in the hydroxyurea arm until a stable maximum tolerated dose (MTD) of hydroxyurea was reached, and were then replaced by serial phlebotomy to reduce iron overload. The MTD was reached after 6 months at an average dose of about 25 mg/kg/day.

The transfusion overlap with hydroxyurea was designed as a safety measure to avoid strokes if monthly transfusions were abruptly discontinued in the hydroxyurea arm before the children had time to achieve MTD.

“The fact that that overlap was about 6 months and the fact we had about 24 months of follow-up tracking the TCD velocities over time, we feel that doesn’t affect the end statistical analysis,” Dr. Ware said.

As for whether hydroxyurea is superior to monthly transfusions, he noted that the trial was not designed for superiority and superiority was seen in a post-hoc analysis. “What we can say with certainty is that it’s non-inferior to the standard treatment,” Dr. Ware said.

The final analysis was based on 42 patients randomized to the transfusion arm who completed all 24 months of treatment, 11 with truncated treatment, and 8 withdrawals, and 41 patients assigned to the hydroxyurea arm who completed all treatment, 13 with truncated treatment and 6 withdrawals.

Sickle cell-related serious adverse events were more common in the hydroxyurea arm than the transfusion arm (23 vs. 15), but none were related to the study drug or procedures.

There were 29 new centrally adjudicated neurological events including 3 transient ischemic attacks in each arm. In the transfusion arm, one child was withdrawn per protocol after developing TCD velocities exceeding 240 cm/sec and a second developed new vasculopathy. The safety of long-term hydroxyurea has been established in multiple pediatric studies, Dr. Ware said.

TWiTCH was funded by the National Heart, Lung and Blood Institute and sponsored by Cincinnati Children’s Hospital Medical Center. Dr. Ware reported serving as a data safety monitoring board member for Eli Lilly, consultancy for Bayer, and research funding from Bristol Myers Squibb. Dr. Thompson disclosed research funding from Amgen, Baxalta, bluebird bio, Celgene, Eli Lilly, GlaxoSmithKline, Mast, and Novartis, and consultancy for ApoPharma, bluebird bio, and Novartis.

[email protected]

ORLANDO – Oral hydroxyurea is as good as chronic red blood cell transfusions for prevention of primary stroke in children at high-risk for this devastating complication of sickle cell disease, results of the TWiTCH study show.

No child suffered a stroke with either hydroxyurea or monthly transfusions and transcranial doppler (TCD) velocities were maintained in both arms.

The study was stopped early, however, after noninferiority was shown for the primary end point of TCD mean velocities on the index side at 24 months, with a post-hoc analysis suggesting hydroxyurea may even be superior, study author Dr. Russell E. Ware, director of hematology at Cincinnati (Ohio) Children’s Hospital Medical Center, reported during the plenary session at the annual meeting of the American Society of Hematology.

Patrice Wendling/Frontline Medical News

“Hydroxyurea therapy can substitute for chronic transfusions to maintain TCD velocities and help prevent primary stroke,” he said during a press briefing.

The final mean TCD velocities were 143 cm/second in the transfusion arm and 138 cm/sec in the hydroxyurea arm, resulting in P values of 8.82 x 10^-16 for non-inferiority by intention-to-treat analysis and 0.023 for superiority in a post-hoc analysis.

Hydroxyurea also had the added benefit of improving iron overload status more than monthly transfusions based on a greater average change in serum ferritin (-1,085 ng/mL vs. -38 ng/mL; P less than .001) and liver iron concentrations (-1.9 mg/g vs. +2.4 mg/g; P = .001), according to their report.

Press briefing moderator Dr. Alexis Thompson, of the Ann & Robert H. Lurie Children’s Hospital of Chicago, commented, “This truly is one of the abstracts that are being presenting at the meeting today that can be defined as practice changing. There are many families who have great difficulty accepting the reality, prior to the TWiTCH study, of their children having to be transfused lifelong.”

Strokes occur in up to 10% of children with sickle cell disease (SCD). Transfusions are effective for stroke prophylaxis in this setting, but have to be continued lifelong and can lead to iron overload and other complications.

Based on the participating sites, at least 80% of children with abnormal TCD velocities currently on blood transfusions to prevent stroke would be eligible for treatment with hydroxyurea, Dr. Ware said.

Hydroxyurea increases the amount of fetal hemoglobin and fetal red blood cells and was approved more than a decade ago to ameliorate the acute and chronic complications of SCD. Its use could provide dramatic cost savings for families since a transfusion costs about $1,000 to $2,000 every month, whereas hydroxyurea costs less than a dollar a day, Dr. Ware said in an interview.

TWiTCH (TCD with Transfusions Changing to Hydroxyurea) was conducted at 26 pediatric programs and used TCD to identify 121 children with SCD who were at elevated risk of stroke based on abnormally high cerebral artery flow velocities of at least 200 cm/sec. The children were evenly randomized to 24 months of treatment. TCD velocities were obtained every 12 weeks and reviewed centrally, with local investigators blinded to the results. All children had received transfusions for at least 12 months, but had not developed severe vasculopathy.

The transfusion arm was maintained at a target hemoglobin S level of less than 30% and chelation used to manage elevated liver concentrations. Transfusions were allowed in the hydroxyurea arm until a stable maximum tolerated dose (MTD) of hydroxyurea was reached, and were then replaced by serial phlebotomy to reduce iron overload. The MTD was reached after 6 months at an average dose of about 25 mg/kg/day.

The transfusion overlap with hydroxyurea was designed as a safety measure to avoid strokes if monthly transfusions were abruptly discontinued in the hydroxyurea arm before the children had time to achieve MTD.

“The fact that that overlap was about 6 months and the fact we had about 24 months of follow-up tracking the TCD velocities over time, we feel that doesn’t affect the end statistical analysis,” Dr. Ware said.

As for whether hydroxyurea is superior to monthly transfusions, he noted that the trial was not designed for superiority and superiority was seen in a post-hoc analysis. “What we can say with certainty is that it’s non-inferior to the standard treatment,” Dr. Ware said.

The final analysis was based on 42 patients randomized to the transfusion arm who completed all 24 months of treatment, 11 with truncated treatment, and 8 withdrawals, and 41 patients assigned to the hydroxyurea arm who completed all treatment, 13 with truncated treatment and 6 withdrawals.

Sickle cell-related serious adverse events were more common in the hydroxyurea arm than the transfusion arm (23 vs. 15), but none were related to the study drug or procedures.

There were 29 new centrally adjudicated neurological events including 3 transient ischemic attacks in each arm. In the transfusion arm, one child was withdrawn per protocol after developing TCD velocities exceeding 240 cm/sec and a second developed new vasculopathy. The safety of long-term hydroxyurea has been established in multiple pediatric studies, Dr. Ware said.

TWiTCH was funded by the National Heart, Lung and Blood Institute and sponsored by Cincinnati Children’s Hospital Medical Center. Dr. Ware reported serving as a data safety monitoring board member for Eli Lilly, consultancy for Bayer, and research funding from Bristol Myers Squibb. Dr. Thompson disclosed research funding from Amgen, Baxalta, bluebird bio, Celgene, Eli Lilly, GlaxoSmithKline, Mast, and Novartis, and consultancy for ApoPharma, bluebird bio, and Novartis.

[email protected]

ORLANDO – Oral hydroxyurea is as good as chronic red blood cell transfusions for prevention of primary stroke in children at high-risk for this devastating complication of sickle cell disease, results of the TWiTCH study show.

No child suffered a stroke with either hydroxyurea or monthly transfusions and transcranial doppler (TCD) velocities were maintained in both arms.

The study was stopped early, however, after noninferiority was shown for the primary end point of TCD mean velocities on the index side at 24 months, with a post-hoc analysis suggesting hydroxyurea may even be superior, study author Dr. Russell E. Ware, director of hematology at Cincinnati (Ohio) Children’s Hospital Medical Center, reported during the plenary session at the annual meeting of the American Society of Hematology.

Patrice Wendling/Frontline Medical News

“Hydroxyurea therapy can substitute for chronic transfusions to maintain TCD velocities and help prevent primary stroke,” he said during a press briefing.

The final mean TCD velocities were 143 cm/second in the transfusion arm and 138 cm/sec in the hydroxyurea arm, resulting in P values of 8.82 x 10^-16 for non-inferiority by intention-to-treat analysis and 0.023 for superiority in a post-hoc analysis.

Hydroxyurea also had the added benefit of improving iron overload status more than monthly transfusions based on a greater average change in serum ferritin (-1,085 ng/mL vs. -38 ng/mL; P less than .001) and liver iron concentrations (-1.9 mg/g vs. +2.4 mg/g; P = .001), according to their report.

Press briefing moderator Dr. Alexis Thompson, of the Ann & Robert H. Lurie Children’s Hospital of Chicago, commented, “This truly is one of the abstracts that are being presenting at the meeting today that can be defined as practice changing. There are many families who have great difficulty accepting the reality, prior to the TWiTCH study, of their children having to be transfused lifelong.”

Strokes occur in up to 10% of children with sickle cell disease (SCD). Transfusions are effective for stroke prophylaxis in this setting, but have to be continued lifelong and can lead to iron overload and other complications.

Based on the participating sites, at least 80% of children with abnormal TCD velocities currently on blood transfusions to prevent stroke would be eligible for treatment with hydroxyurea, Dr. Ware said.

Hydroxyurea increases the amount of fetal hemoglobin and fetal red blood cells and was approved more than a decade ago to ameliorate the acute and chronic complications of SCD. Its use could provide dramatic cost savings for families since a transfusion costs about $1,000 to $2,000 every month, whereas hydroxyurea costs less than a dollar a day, Dr. Ware said in an interview.

TWiTCH (TCD with Transfusions Changing to Hydroxyurea) was conducted at 26 pediatric programs and used TCD to identify 121 children with SCD who were at elevated risk of stroke based on abnormally high cerebral artery flow velocities of at least 200 cm/sec. The children were evenly randomized to 24 months of treatment. TCD velocities were obtained every 12 weeks and reviewed centrally, with local investigators blinded to the results. All children had received transfusions for at least 12 months, but had not developed severe vasculopathy.

The transfusion arm was maintained at a target hemoglobin S level of less than 30% and chelation used to manage elevated liver concentrations. Transfusions were allowed in the hydroxyurea arm until a stable maximum tolerated dose (MTD) of hydroxyurea was reached, and were then replaced by serial phlebotomy to reduce iron overload. The MTD was reached after 6 months at an average dose of about 25 mg/kg/day.

The transfusion overlap with hydroxyurea was designed as a safety measure to avoid strokes if monthly transfusions were abruptly discontinued in the hydroxyurea arm before the children had time to achieve MTD.

“The fact that that overlap was about 6 months and the fact we had about 24 months of follow-up tracking the TCD velocities over time, we feel that doesn’t affect the end statistical analysis,” Dr. Ware said.

As for whether hydroxyurea is superior to monthly transfusions, he noted that the trial was not designed for superiority and superiority was seen in a post-hoc analysis. “What we can say with certainty is that it’s non-inferior to the standard treatment,” Dr. Ware said.

The final analysis was based on 42 patients randomized to the transfusion arm who completed all 24 months of treatment, 11 with truncated treatment, and 8 withdrawals, and 41 patients assigned to the hydroxyurea arm who completed all treatment, 13 with truncated treatment and 6 withdrawals.

Sickle cell-related serious adverse events were more common in the hydroxyurea arm than the transfusion arm (23 vs. 15), but none were related to the study drug or procedures.

There were 29 new centrally adjudicated neurological events including 3 transient ischemic attacks in each arm. In the transfusion arm, one child was withdrawn per protocol after developing TCD velocities exceeding 240 cm/sec and a second developed new vasculopathy. The safety of long-term hydroxyurea has been established in multiple pediatric studies, Dr. Ware said.

TWiTCH was funded by the National Heart, Lung and Blood Institute and sponsored by Cincinnati Children’s Hospital Medical Center. Dr. Ware reported serving as a data safety monitoring board member for Eli Lilly, consultancy for Bayer, and research funding from Bristol Myers Squibb. Dr. Thompson disclosed research funding from Amgen, Baxalta, bluebird bio, Celgene, Eli Lilly, GlaxoSmithKline, Mast, and Novartis, and consultancy for ApoPharma, bluebird bio, and Novartis.

[email protected]

Prescription drugs

Photo by Steven Harbour

The US Food and Drug Administration (FDA) has approved the use of imatinib mesylate, a generic version of Novartis’s Gleevec being developed by a subsidiary of Sun Pharmaceuticals Limited.

Under the terms of a settlement agreement with Novartis, the Sun Pharma subsidiary is allowed to launch its generic imatinib in the US on February 1, 2016.

The drug will be available in 100 mg and 400 mg tablets.

The Sun Pharma subsidiary was the first company to file an abbreviated new drug application for generic imatinib with a para IV certification and is therefore eligible for 180 days of marketing exclusivity in the US.

Sun Pharma’s imatinib mesylate is approved for the following indications:

• Newly diagnosed adult and pediatric patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase
• Patients with (Ph+ CML) in blast crisis, accelerated phase, or in chronic phase after failure of interferon-alpha therapy
• Adult patients with relapsed or refractory Ph+ acute lymphoblastic leukemia
• Adult patients with myelodysplastic/myeloproliferative diseases associated with PDGFR gene re-arrangements
• Adult patients with aggressive systemic mastocytosis without the D816V c-Kit mutation or with c-Kit mutational status unknown
•  Adult patients with hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukemia (CEL) who have the FIP1L1-PDGFRα fusion kinase and for patients with HES and/or CEL who are FIP1L1- PDGFRα fusion kinase negative or unknown
• Adult patients with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans.

The drug is not approved to treat patients with KIT (CD117)-positive unresectable and/or metastatic malignant gastrointestinal stromal tumors.

Prescription drugs

Photo by Steven Harbour

The US Food and Drug Administration (FDA) has approved the use of imatinib mesylate, a generic version of Novartis’s Gleevec being developed by a subsidiary of Sun Pharmaceuticals Limited.

Under the terms of a settlement agreement with Novartis, the Sun Pharma subsidiary is allowed to launch its generic imatinib in the US on February 1, 2016.

The drug will be available in 100 mg and 400 mg tablets.

The Sun Pharma subsidiary was the first company to file an abbreviated new drug application for generic imatinib with a para IV certification and is therefore eligible for 180 days of marketing exclusivity in the US.

Sun Pharma’s imatinib mesylate is approved for the following indications:

• Newly diagnosed adult and pediatric patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase
• Patients with (Ph+ CML) in blast crisis, accelerated phase, or in chronic phase after failure of interferon-alpha therapy
• Adult patients with relapsed or refractory Ph+ acute lymphoblastic leukemia
• Adult patients with myelodysplastic/myeloproliferative diseases associated with PDGFR gene re-arrangements
• Adult patients with aggressive systemic mastocytosis without the D816V c-Kit mutation or with c-Kit mutational status unknown
•  Adult patients with hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukemia (CEL) who have the FIP1L1-PDGFRα fusion kinase and for patients with HES and/or CEL who are FIP1L1- PDGFRα fusion kinase negative or unknown
• Adult patients with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans.

The drug is not approved to treat patients with KIT (CD117)-positive unresectable and/or metastatic malignant gastrointestinal stromal tumors.

Prescription drugs

Photo by Steven Harbour

The US Food and Drug Administration (FDA) has approved the use of imatinib mesylate, a generic version of Novartis’s Gleevec being developed by a subsidiary of Sun Pharmaceuticals Limited.

Under the terms of a settlement agreement with Novartis, the Sun Pharma subsidiary is allowed to launch its generic imatinib in the US on February 1, 2016.

The drug will be available in 100 mg and 400 mg tablets.

The Sun Pharma subsidiary was the first company to file an abbreviated new drug application for generic imatinib with a para IV certification and is therefore eligible for 180 days of marketing exclusivity in the US.

Sun Pharma’s imatinib mesylate is approved for the following indications:

• Newly diagnosed adult and pediatric patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase
• Patients with (Ph+ CML) in blast crisis, accelerated phase, or in chronic phase after failure of interferon-alpha therapy
• Adult patients with relapsed or refractory Ph+ acute lymphoblastic leukemia
• Adult patients with myelodysplastic/myeloproliferative diseases associated with PDGFR gene re-arrangements
• Adult patients with aggressive systemic mastocytosis without the D816V c-Kit mutation or with c-Kit mutational status unknown
•  Adult patients with hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukemia (CEL) who have the FIP1L1-PDGFRα fusion kinase and for patients with HES and/or CEL who are FIP1L1- PDGFRα fusion kinase negative or unknown
• Adult patients with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans.

The drug is not approved to treat patients with KIT (CD117)-positive unresectable and/or metastatic malignant gastrointestinal stromal tumors.

ORLANDO – Lentiviral gene therapy with LentiGlobin BB305 boosts beta-globin production in patients with beta-thalassemia, but frees only some from lifelong dependence on blood transfusions, updated results of the Northstar study show.

Five patients with non-Beta-0/Beta-0 genotypes were able to stop transfusions shortly after their infusion, and remain transfusion independent for up to 16.4 months.

In four patients with the more severe form of beta-thalassemia, the Beta-0/Beta-0 genotype, red blood cell transfusion volume was reduced by 33% to 100%, with one patient stopping transfusions entirely, Dr. Mark C. Walters of the University of California-San Francisco Benioff Children’s Hospital in Oakland reported at the annual meeting of the American Society of Hematology.

Preliminary findings reported over the last two years have raised hopes that the experimental lentiviral-based therapy could be a functional cure for beta-thalassemia major and severe sickle cell disease.

Patients with beta-thalassemia major, also called Cooley’s anemia, rely on frequent blood transfusions to correct the anemia, with less than a quarter undergoing curative treatment with an allogeneic hematopoietic transplant.

In the ongoing Northstar study, 13 patients with transfusion-dependent beta-thalassemia major have been infused as of Oct. 28, 2015 with autologous CD34-positive cells transduced ex-vivo with LentiGlobin BB305 (Bluebird bio, Cambridge, Mass.), a self-inactivating, second-generation lentiviral vector containing a functioning, engineered beta-globin gene (A-T87Q). Their median age was 21 years and 11 were women.Vector-derived hemoglobin A^T87Q was detectable at 6 months in 8 of 9 evaluable patients with at least six months follow-up and in 100% at 9 months, Dr. Walters reported. The median HbA^T87Q level was 4.9 g/dL at 6 months, 6.5 g/dL at 9 months, and 4.2 g/dL at 12 months.

The difference in transfusion independence between genotypes is explained by endogenous non-HbAT87Q production, he said during a press briefing. While lentiglobin production was the same in patients with Beta-0/Beta-0 and non-Beta-0/Beta-0 genotypes, the Beta-0/Beta-0 patients made much smaller amounts of native hemoglobin.

Three serious post-infusion events occurred: grade 2 thrombosis, grade 3 skin infection and grade 3 veno-occlusive liver disease.

Importantly, there was no evidence of clonal dominance or replication competent lentivirus with up to 19 months follow-up.

“This is a significant advancement in the treatment of thalassemia for several reasons,” Dr. Walters told reporters. “First, compared to a bone marrow transplant, which is the only curative therapy that’s been approved, this appears to be a safer treatment in that none of these patients had a life-threatening complication. Second, because the treatment uses a thalassemia patient’s own stem cells, this bypasses the need to find a healthy bone marrow donor and thus should be more broadly available to patients affected by this disease.”

Dr. George Daley of Harvard Medical School in Boston and moderator of the press briefing, agreed that the results are an welcome advancement after decades of disappointments in the field of gene therapy including the development of insertional mutigenesis.

In addition to the Northstar study (Ab. 201), results will be presented at the meeting from a second study examining LentiGlobin BB305 gene therapy for severe sickle cell disease and beta-thalassemia major (Ab. 202) and from the recently expanded phase I HGB-206 study in severe sickle cell disease (Ab. 3233).

Sickle cell disease represents a much larger potential market for LentiGlobin BB305, with an estimated 90,000 to 100,000 Americans affected compared with about 15,000 patients in America and Europe living with beta-thalassemia major.

[email protected]

ORLANDO – Lentiviral gene therapy with LentiGlobin BB305 boosts beta-globin production in patients with beta-thalassemia, but frees only some from lifelong dependence on blood transfusions, updated results of the Northstar study show.

Five patients with non-Beta-0/Beta-0 genotypes were able to stop transfusions shortly after their infusion, and remain transfusion independent for up to 16.4 months.

In four patients with the more severe form of beta-thalassemia, the Beta-0/Beta-0 genotype, red blood cell transfusion volume was reduced by 33% to 100%, with one patient stopping transfusions entirely, Dr. Mark C. Walters of the University of California-San Francisco Benioff Children’s Hospital in Oakland reported at the annual meeting of the American Society of Hematology.

Preliminary findings reported over the last two years have raised hopes that the experimental lentiviral-based therapy could be a functional cure for beta-thalassemia major and severe sickle cell disease.

Patients with beta-thalassemia major, also called Cooley’s anemia, rely on frequent blood transfusions to correct the anemia, with less than a quarter undergoing curative treatment with an allogeneic hematopoietic transplant.

In the ongoing Northstar study, 13 patients with transfusion-dependent beta-thalassemia major have been infused as of Oct. 28, 2015 with autologous CD34-positive cells transduced ex-vivo with LentiGlobin BB305 (Bluebird bio, Cambridge, Mass.), a self-inactivating, second-generation lentiviral vector containing a functioning, engineered beta-globin gene (A-T87Q). Their median age was 21 years and 11 were women.Vector-derived hemoglobin A^T87Q was detectable at 6 months in 8 of 9 evaluable patients with at least six months follow-up and in 100% at 9 months, Dr. Walters reported. The median HbA^T87Q level was 4.9 g/dL at 6 months, 6.5 g/dL at 9 months, and 4.2 g/dL at 12 months.

The difference in transfusion independence between genotypes is explained by endogenous non-HbAT87Q production, he said during a press briefing. While lentiglobin production was the same in patients with Beta-0/Beta-0 and non-Beta-0/Beta-0 genotypes, the Beta-0/Beta-0 patients made much smaller amounts of native hemoglobin.

Three serious post-infusion events occurred: grade 2 thrombosis, grade 3 skin infection and grade 3 veno-occlusive liver disease.

Importantly, there was no evidence of clonal dominance or replication competent lentivirus with up to 19 months follow-up.

“This is a significant advancement in the treatment of thalassemia for several reasons,” Dr. Walters told reporters. “First, compared to a bone marrow transplant, which is the only curative therapy that’s been approved, this appears to be a safer treatment in that none of these patients had a life-threatening complication. Second, because the treatment uses a thalassemia patient’s own stem cells, this bypasses the need to find a healthy bone marrow donor and thus should be more broadly available to patients affected by this disease.”

Dr. George Daley of Harvard Medical School in Boston and moderator of the press briefing, agreed that the results are an welcome advancement after decades of disappointments in the field of gene therapy including the development of insertional mutigenesis.

In addition to the Northstar study (Ab. 201), results will be presented at the meeting from a second study examining LentiGlobin BB305 gene therapy for severe sickle cell disease and beta-thalassemia major (Ab. 202) and from the recently expanded phase I HGB-206 study in severe sickle cell disease (Ab. 3233).

Sickle cell disease represents a much larger potential market for LentiGlobin BB305, with an estimated 90,000 to 100,000 Americans affected compared with about 15,000 patients in America and Europe living with beta-thalassemia major.

[email protected]

ORLANDO – Lentiviral gene therapy with LentiGlobin BB305 boosts beta-globin production in patients with beta-thalassemia, but frees only some from lifelong dependence on blood transfusions, updated results of the Northstar study show.

Five patients with non-Beta-0/Beta-0 genotypes were able to stop transfusions shortly after their infusion, and remain transfusion independent for up to 16.4 months.

In four patients with the more severe form of beta-thalassemia, the Beta-0/Beta-0 genotype, red blood cell transfusion volume was reduced by 33% to 100%, with one patient stopping transfusions entirely, Dr. Mark C. Walters of the University of California-San Francisco Benioff Children’s Hospital in Oakland reported at the annual meeting of the American Society of Hematology.

Preliminary findings reported over the last two years have raised hopes that the experimental lentiviral-based therapy could be a functional cure for beta-thalassemia major and severe sickle cell disease.

Patients with beta-thalassemia major, also called Cooley’s anemia, rely on frequent blood transfusions to correct the anemia, with less than a quarter undergoing curative treatment with an allogeneic hematopoietic transplant.

In the ongoing Northstar study, 13 patients with transfusion-dependent beta-thalassemia major have been infused as of Oct. 28, 2015 with autologous CD34-positive cells transduced ex-vivo with LentiGlobin BB305 (Bluebird bio, Cambridge, Mass.), a self-inactivating, second-generation lentiviral vector containing a functioning, engineered beta-globin gene (A-T87Q). Their median age was 21 years and 11 were women.Vector-derived hemoglobin A^T87Q was detectable at 6 months in 8 of 9 evaluable patients with at least six months follow-up and in 100% at 9 months, Dr. Walters reported. The median HbA^T87Q level was 4.9 g/dL at 6 months, 6.5 g/dL at 9 months, and 4.2 g/dL at 12 months.

The difference in transfusion independence between genotypes is explained by endogenous non-HbAT87Q production, he said during a press briefing. While lentiglobin production was the same in patients with Beta-0/Beta-0 and non-Beta-0/Beta-0 genotypes, the Beta-0/Beta-0 patients made much smaller amounts of native hemoglobin.

Three serious post-infusion events occurred: grade 2 thrombosis, grade 3 skin infection and grade 3 veno-occlusive liver disease.

Importantly, there was no evidence of clonal dominance or replication competent lentivirus with up to 19 months follow-up.

“This is a significant advancement in the treatment of thalassemia for several reasons,” Dr. Walters told reporters. “First, compared to a bone marrow transplant, which is the only curative therapy that’s been approved, this appears to be a safer treatment in that none of these patients had a life-threatening complication. Second, because the treatment uses a thalassemia patient’s own stem cells, this bypasses the need to find a healthy bone marrow donor and thus should be more broadly available to patients affected by this disease.”

Dr. George Daley of Harvard Medical School in Boston and moderator of the press briefing, agreed that the results are an welcome advancement after decades of disappointments in the field of gene therapy including the development of insertional mutigenesis.

In addition to the Northstar study (Ab. 201), results will be presented at the meeting from a second study examining LentiGlobin BB305 gene therapy for severe sickle cell disease and beta-thalassemia major (Ab. 202) and from the recently expanded phase I HGB-206 study in severe sickle cell disease (Ab. 3233).

Sickle cell disease represents a much larger potential market for LentiGlobin BB305, with an estimated 90,000 to 100,000 Americans affected compared with about 15,000 patients in America and Europe living with beta-thalassemia major.

[email protected]

Blood donation

A device used to measure hemoglobin can deliver inaccurate results and may have prompted an increase in anemia among blood donors in Ireland, according to the Irish Blood Transfusion Service (IBTS).

The IBTS began using the device—called haemospect—in July 2014 but recently discovered that it cannot detect anemia accurately in all cases.

This may have resulted in anemic individuals donating blood or caused individuals to become anemic by donating.

The IBTS said this issue likely affected female donors more than males, so the organization has decided to temporarily stop taking blood donations from women who have donated in the last 18 months.

The IBTS also said it will perform a full blood count on all male and female donors going forward, until this issue has been resolved.

“Until we have a resolution to the problem that has arisen, we are asking male donors to attend our clinics and give blood,” said IBTS Medical and Scientific Director William Murphy, MD.

“We need male donors to make an extra effort to donate and maintain the blood supply. We will be double-checking all hemoglobin results on these donors.”

Discovering the problem

Haemospect is a noninvasive device that uses white light to detect hemoglobin levels. The device is made by the German company MBR Optical Systems.

IBTS learned of the potential for inaccuracies with haemospect after a blood donor contacted the organization. She had been diagnosed as severely anemic by her doctor but had given blood the week before.

“We have now discovered that the device gives inaccurate results in some individuals with anemia down to, and probably below, 8.4 g/dL,” Dr Murphy said. “As a result of the issue . . . , some women, and probably a much smaller number of men, could have been rendered iron-deficient and anemic from blood donation in the past 18 months.”

Steps to resolution

Since the issue was discovered, more than 30 women with anemia have been identified and contacted. The IBTS said it will contact all donors who are found to be anemic.

“Over the next few weeks, we will introduce new software to reanalyze all the electronic results from all donors who have been tested and accepted for donation since we introduced this device,” Dr Murphy said. “Any discrepant results will be notified to the donors involved.”

Dr Murphy also said donors who think they might be anemic or iron-deficient should visit their doctors for testing, and the IBTS will foot the bill. Concerned donors can contact the IBTS at 1850 731137.

The IBTS plans to replace haemospect with an alternative device as soon as possible. The organization has contacted the Health Products Regularity Authority about the issue with haemospect, which is used in Austria and Germany as well.

“We are determined to have this matter resolved as soon as possible,” Dr Murphy said. “We are confident that this issue . . . has not had any impact on blood received by patients.”

Blood donation

A device used to measure hemoglobin can deliver inaccurate results and may have prompted an increase in anemia among blood donors in Ireland, according to the Irish Blood Transfusion Service (IBTS).

The IBTS began using the device—called haemospect—in July 2014 but recently discovered that it cannot detect anemia accurately in all cases.

This may have resulted in anemic individuals donating blood or caused individuals to become anemic by donating.

The IBTS said this issue likely affected female donors more than males, so the organization has decided to temporarily stop taking blood donations from women who have donated in the last 18 months.

The IBTS also said it will perform a full blood count on all male and female donors going forward, until this issue has been resolved.

“Until we have a resolution to the problem that has arisen, we are asking male donors to attend our clinics and give blood,” said IBTS Medical and Scientific Director William Murphy, MD.

“We need male donors to make an extra effort to donate and maintain the blood supply. We will be double-checking all hemoglobin results on these donors.”

Discovering the problem

Haemospect is a noninvasive device that uses white light to detect hemoglobin levels. The device is made by the German company MBR Optical Systems.

IBTS learned of the potential for inaccuracies with haemospect after a blood donor contacted the organization. She had been diagnosed as severely anemic by her doctor but had given blood the week before.

“We have now discovered that the device gives inaccurate results in some individuals with anemia down to, and probably below, 8.4 g/dL,” Dr Murphy said. “As a result of the issue . . . , some women, and probably a much smaller number of men, could have been rendered iron-deficient and anemic from blood donation in the past 18 months.”

Steps to resolution

Since the issue was discovered, more than 30 women with anemia have been identified and contacted. The IBTS said it will contact all donors who are found to be anemic.

“Over the next few weeks, we will introduce new software to reanalyze all the electronic results from all donors who have been tested and accepted for donation since we introduced this device,” Dr Murphy said. “Any discrepant results will be notified to the donors involved.”

Dr Murphy also said donors who think they might be anemic or iron-deficient should visit their doctors for testing, and the IBTS will foot the bill. Concerned donors can contact the IBTS at 1850 731137.

The IBTS plans to replace haemospect with an alternative device as soon as possible. The organization has contacted the Health Products Regularity Authority about the issue with haemospect, which is used in Austria and Germany as well.

“We are determined to have this matter resolved as soon as possible,” Dr Murphy said. “We are confident that this issue . . . has not had any impact on blood received by patients.”

Blood donation

A device used to measure hemoglobin can deliver inaccurate results and may have prompted an increase in anemia among blood donors in Ireland, according to the Irish Blood Transfusion Service (IBTS).

The IBTS began using the device—called haemospect—in July 2014 but recently discovered that it cannot detect anemia accurately in all cases.

This may have resulted in anemic individuals donating blood or caused individuals to become anemic by donating.

The IBTS said this issue likely affected female donors more than males, so the organization has decided to temporarily stop taking blood donations from women who have donated in the last 18 months.

The IBTS also said it will perform a full blood count on all male and female donors going forward, until this issue has been resolved.

“Until we have a resolution to the problem that has arisen, we are asking male donors to attend our clinics and give blood,” said IBTS Medical and Scientific Director William Murphy, MD.

“We need male donors to make an extra effort to donate and maintain the blood supply. We will be double-checking all hemoglobin results on these donors.”

Discovering the problem

Haemospect is a noninvasive device that uses white light to detect hemoglobin levels. The device is made by the German company MBR Optical Systems.

IBTS learned of the potential for inaccuracies with haemospect after a blood donor contacted the organization. She had been diagnosed as severely anemic by her doctor but had given blood the week before.

“We have now discovered that the device gives inaccurate results in some individuals with anemia down to, and probably below, 8.4 g/dL,” Dr Murphy said. “As a result of the issue . . . , some women, and probably a much smaller number of men, could have been rendered iron-deficient and anemic from blood donation in the past 18 months.”

Steps to resolution

Since the issue was discovered, more than 30 women with anemia have been identified and contacted. The IBTS said it will contact all donors who are found to be anemic.

“Over the next few weeks, we will introduce new software to reanalyze all the electronic results from all donors who have been tested and accepted for donation since we introduced this device,” Dr Murphy said. “Any discrepant results will be notified to the donors involved.”

Dr Murphy also said donors who think they might be anemic or iron-deficient should visit their doctors for testing, and the IBTS will foot the bill. Concerned donors can contact the IBTS at 1850 731137.

The IBTS plans to replace haemospect with an alternative device as soon as possible. The organization has contacted the Health Products Regularity Authority about the issue with haemospect, which is used in Austria and Germany as well.

“We are determined to have this matter resolved as soon as possible,” Dr Murphy said. “We are confident that this issue . . . has not had any impact on blood received by patients.”

Proliferating HSCs

Image by John Perry

Previous studies have shown that hematopoietic stresses—such as myelofibrosis, anemia, and myeloablation—can induce extramedullary hematopoiesis (EMH), in which hematopoietic stem cells (HSCs) are mobilized to sites outside the bone marrow.

The splenic red pulp is known to be a prominent site of EMH in both mice and humans, but not much is known about the EMH niche.

Now, investigators say they have characterized this niche.

They detailed their findings in Nature.

The team used mouse models to examine the expression patterns of 2 known niche cell factors, SCF and CXCL12.

They discovered that the hematopoietic microenvironment in the spleen is found near sinusoidal blood vessels and is created by endothelial cells and perivascular stromal cells, just like the microenvironment in the bone marrow.

“Under emergency conditions, the endothelial cells and perivascular stromal cells that reside in the spleen are induced to proliferate so they can sustain all the new blood-forming stem cells that migrate into the spleen,” explained study author Sean Morrison, PhD, of the University of Texas Southwestern Medical Center, Dallas.

“We determined that this process in the spleen is physiologically important for responding to hematopoietic stress. Without it, the mice we studied could not maintain normal blood cell counts during pregnancy or quickly regenerate blood cell counts after bleeding or chemotherapy.”

The investigators believe these findings could aid the development of therapeutic interventions to enhance blood formation following chemotherapy or HSC transplant and thus accelerate the recovery of blood cell counts.

Proliferating HSCs

Image by John Perry

Previous studies have shown that hematopoietic stresses—such as myelofibrosis, anemia, and myeloablation—can induce extramedullary hematopoiesis (EMH), in which hematopoietic stem cells (HSCs) are mobilized to sites outside the bone marrow.

The splenic red pulp is known to be a prominent site of EMH in both mice and humans, but not much is known about the EMH niche.

Now, investigators say they have characterized this niche.

They detailed their findings in Nature.

The team used mouse models to examine the expression patterns of 2 known niche cell factors, SCF and CXCL12.

They discovered that the hematopoietic microenvironment in the spleen is found near sinusoidal blood vessels and is created by endothelial cells and perivascular stromal cells, just like the microenvironment in the bone marrow.

“Under emergency conditions, the endothelial cells and perivascular stromal cells that reside in the spleen are induced to proliferate so they can sustain all the new blood-forming stem cells that migrate into the spleen,” explained study author Sean Morrison, PhD, of the University of Texas Southwestern Medical Center, Dallas.

“We determined that this process in the spleen is physiologically important for responding to hematopoietic stress. Without it, the mice we studied could not maintain normal blood cell counts during pregnancy or quickly regenerate blood cell counts after bleeding or chemotherapy.”

The investigators believe these findings could aid the development of therapeutic interventions to enhance blood formation following chemotherapy or HSC transplant and thus accelerate the recovery of blood cell counts.

Proliferating HSCs

Image by John Perry

Previous studies have shown that hematopoietic stresses—such as myelofibrosis, anemia, and myeloablation—can induce extramedullary hematopoiesis (EMH), in which hematopoietic stem cells (HSCs) are mobilized to sites outside the bone marrow.

The splenic red pulp is known to be a prominent site of EMH in both mice and humans, but not much is known about the EMH niche.

Now, investigators say they have characterized this niche.

They detailed their findings in Nature.

The team used mouse models to examine the expression patterns of 2 known niche cell factors, SCF and CXCL12.

They discovered that the hematopoietic microenvironment in the spleen is found near sinusoidal blood vessels and is created by endothelial cells and perivascular stromal cells, just like the microenvironment in the bone marrow.

“Under emergency conditions, the endothelial cells and perivascular stromal cells that reside in the spleen are induced to proliferate so they can sustain all the new blood-forming stem cells that migrate into the spleen,” explained study author Sean Morrison, PhD, of the University of Texas Southwestern Medical Center, Dallas.

“We determined that this process in the spleen is physiologically important for responding to hematopoietic stress. Without it, the mice we studied could not maintain normal blood cell counts during pregnancy or quickly regenerate blood cell counts after bleeding or chemotherapy.”

The investigators believe these findings could aid the development of therapeutic interventions to enhance blood formation following chemotherapy or HSC transplant and thus accelerate the recovery of blood cell counts.

Iron dextran drip

Photo from Flickr

Researchers have compared the risk of anaphylaxis with different intravenous (IV) iron products and found evidence to suggest that iron dextran poses the greatest risk.

Compared with nondextran formulations, iron dextran was associated with a higher cumulative risk of anaphylaxis and an increased risk of anaphylaxis at first administration.

Iron sucrose was associated with the lowest risk of anaphylaxis, both cumulative and at first administration.

Cunlin Wang, MD, PhD, of the US Food and Drug Administration in Silver Spring, Maryland, and his colleagues conducted this research and reported the results in JAMA.

The researchers studied 688,183 recipients of IV iron enrolled in the fee-for-service Medicare program from January 2003 to December 2013.

The team examined administrations of IV iron dextran, gluconate, sucrose, or ferumoxytol. They identified 247,500 iron dextran and 440,683 nondextran users during the study period.

Overall, there were 274 cases of anaphylaxis at first exposure to IV iron and an additional 170 cases during subsequent iron administrations.

At first administration, iron dextran was associated with a higher anaphylaxis risk than nondextran formulations.  The risk of anaphylaxis was 68 per 100,000 persons for iron dextran and 24 per 100,000 persons for all nondextran products combined. The odds ratio—adjusted for age, indication, history of coronary heart disease, and hypertension—was 2.6 (P<0.001).

Among the nondextran products, the risk of anaphylaxis at first administration was higher with both iron gluconate and ferumoxytol than with iron sucrose. When compared with iron sucrose, the adjusted odds ratio of anaphylaxis was 3.6 for iron dextran, 2.0 for iron gluconate, and 2.2 for ferumoxytol.

Because each IV iron product has a specific recommended dose and schedule of administration, the researchers also calculated the cumulative risk of anaphylaxis based on both the number of administrations and the clinically relevant repletion level of iron (1000 mg) achieved within 12 weeks.

The cumulative risk of anaphylaxis over multiple administrations was highest for iron dextran, followed by ferumoxytol, iron gluconate, and iron sucrose.

The estimated cumulative anaphylaxis risk following total iron repletion of 1000 mg administered within a 12-week period was highest with iron dextran (82 per 100,000 persons) and lowest with iron sucrose (21 per 100,000 persons).

The researchers noted that the mechanism of anaphylactic reaction after IV iron remains unknown.

Iron dextran drip

Photo from Flickr

Researchers have compared the risk of anaphylaxis with different intravenous (IV) iron products and found evidence to suggest that iron dextran poses the greatest risk.

Compared with nondextran formulations, iron dextran was associated with a higher cumulative risk of anaphylaxis and an increased risk of anaphylaxis at first administration.

Iron sucrose was associated with the lowest risk of anaphylaxis, both cumulative and at first administration.

Cunlin Wang, MD, PhD, of the US Food and Drug Administration in Silver Spring, Maryland, and his colleagues conducted this research and reported the results in JAMA.

The researchers studied 688,183 recipients of IV iron enrolled in the fee-for-service Medicare program from January 2003 to December 2013.

The team examined administrations of IV iron dextran, gluconate, sucrose, or ferumoxytol. They identified 247,500 iron dextran and 440,683 nondextran users during the study period.

Overall, there were 274 cases of anaphylaxis at first exposure to IV iron and an additional 170 cases during subsequent iron administrations.

At first administration, iron dextran was associated with a higher anaphylaxis risk than nondextran formulations.  The risk of anaphylaxis was 68 per 100,000 persons for iron dextran and 24 per 100,000 persons for all nondextran products combined. The odds ratio—adjusted for age, indication, history of coronary heart disease, and hypertension—was 2.6 (P<0.001).

Among the nondextran products, the risk of anaphylaxis at first administration was higher with both iron gluconate and ferumoxytol than with iron sucrose. When compared with iron sucrose, the adjusted odds ratio of anaphylaxis was 3.6 for iron dextran, 2.0 for iron gluconate, and 2.2 for ferumoxytol.

Because each IV iron product has a specific recommended dose and schedule of administration, the researchers also calculated the cumulative risk of anaphylaxis based on both the number of administrations and the clinically relevant repletion level of iron (1000 mg) achieved within 12 weeks.

The cumulative risk of anaphylaxis over multiple administrations was highest for iron dextran, followed by ferumoxytol, iron gluconate, and iron sucrose.

The estimated cumulative anaphylaxis risk following total iron repletion of 1000 mg administered within a 12-week period was highest with iron dextran (82 per 100,000 persons) and lowest with iron sucrose (21 per 100,000 persons).

The researchers noted that the mechanism of anaphylactic reaction after IV iron remains unknown.

Iron dextran drip

Photo from Flickr

Researchers have compared the risk of anaphylaxis with different intravenous (IV) iron products and found evidence to suggest that iron dextran poses the greatest risk.

Compared with nondextran formulations, iron dextran was associated with a higher cumulative risk of anaphylaxis and an increased risk of anaphylaxis at first administration.

Iron sucrose was associated with the lowest risk of anaphylaxis, both cumulative and at first administration.

Cunlin Wang, MD, PhD, of the US Food and Drug Administration in Silver Spring, Maryland, and his colleagues conducted this research and reported the results in JAMA.

The researchers studied 688,183 recipients of IV iron enrolled in the fee-for-service Medicare program from January 2003 to December 2013.

The team examined administrations of IV iron dextran, gluconate, sucrose, or ferumoxytol. They identified 247,500 iron dextran and 440,683 nondextran users during the study period.

Overall, there were 274 cases of anaphylaxis at first exposure to IV iron and an additional 170 cases during subsequent iron administrations.

At first administration, iron dextran was associated with a higher anaphylaxis risk than nondextran formulations.  The risk of anaphylaxis was 68 per 100,000 persons for iron dextran and 24 per 100,000 persons for all nondextran products combined. The odds ratio—adjusted for age, indication, history of coronary heart disease, and hypertension—was 2.6 (P<0.001).

Among the nondextran products, the risk of anaphylaxis at first administration was higher with both iron gluconate and ferumoxytol than with iron sucrose. When compared with iron sucrose, the adjusted odds ratio of anaphylaxis was 3.6 for iron dextran, 2.0 for iron gluconate, and 2.2 for ferumoxytol.

Because each IV iron product has a specific recommended dose and schedule of administration, the researchers also calculated the cumulative risk of anaphylaxis based on both the number of administrations and the clinically relevant repletion level of iron (1000 mg) achieved within 12 weeks.

The cumulative risk of anaphylaxis over multiple administrations was highest for iron dextran, followed by ferumoxytol, iron gluconate, and iron sucrose.

The estimated cumulative anaphylaxis risk following total iron repletion of 1000 mg administered within a 12-week period was highest with iron dextran (82 per 100,000 persons) and lowest with iron sucrose (21 per 100,000 persons).

The researchers noted that the mechanism of anaphylactic reaction after IV iron remains unknown.

FROM A TELECONFERENCE – The American Society of Hematology’s (ASH) 57th annual meeting in Orlando is chock-full of much-anticipated results in cancer immunotherapies such as CAR T cell therapies and checkpoint inhibitors, advances in sickle cell disease, and practical advice on managing the latest drugs in the clinic, ASH officials said in a teleconference. Here are some of the day-by-day picks selected by ASH president Dr. David Williams and ASH secretary Dr. Stephanie J. Lee, who gave their recommendations during a conference call for the press. Meeting abstracts are now available online.

Saturday, Dec. 5

Clinical applications of newly approved drugs

The popular special education session on clinical applications of newly approved drugs returns on Saturday, Dec. 5 at 9:30 a.m., with didactic presentations that address issues clinicians may face such as drug-drug interactions, side effects, and adverse events. The three drugs to be discussed this year are: idarucizumab (Praxbind), the first specific reversal agent approved for dabigatran reversal; blinatumomab (Blincyto), approved for second-line treatment of Philadelphia chromosomenegative acute lymphoblastic leukemia; and the histone deacetylase (HDAC) inhibitor panobinostat (Farydak), approved for the treatment of multiple myeloma.

Adoptive immunotherapy

One presentation to look out for next month is abstract 99at 12:30 p.m. on Saturday, Dec. 5 in the adoptive immunotherapy session, Dr. Williams told reporters. The chimeric antigen receptor (CAR)-T-cell approach has relied on genetically engineering the patient’s own T cells to rev up the immune system. This group’s approach is to treat B-cell malignancies after allogeneic hematopoietic stem cell transplantation using a single infusion of anti-CD19 CAR-T cells from the patient’s transplant donor.

Eight of 20 patients treated with this strategy achieved remission, including six complete remissions and two partial remissions. Importantly, none of these patients developed acute graft-versus-host disease, a potential consequence of using allogeneic rather than autologous T cells, he said. The authors also noted that patients who responded and went into remission were marked by higher numbers of these infused CAR-T cells in their circulation, suggesting a biomarker of response.

Checkpoint, please?

Immunotherapy is a “very hot area,” so ASH has put together a special session at 4 p.m. Saturday called “Checkpoint, Please?” Dr. Williams said. Topics include the role of programmed death (PD)-1 and PD-ligand 1 in acute and chronic graft-versus-host disease, checkpoint blockade with neoantigen cancer vaccines, and insights into the mechanisms of action of anti-CTLA-4 (cytotoxic T-lymphocyte–associated protein 4) antibody therapy.

Sunday, Dec. 6

Precision medicine

Sunday’s plenary scientific session will include several noteworthy personalized medicine abstracts featuring emerging therapies targeted to specific genetic subtypes, Dr. Lee, from the University of Washington, Seattle, said.

Plenary abstract 6 is a large, multinational study looking at whether adding the multikinase inhibitor midostaurin to standard induction therapy and carried through 1 year of maintenance would improve outcomes in newly diagnosed acute myeloid leukemia with FLT3 mutations. Patients with these deleterious mutations do enter remission with chemotherapy, but often relapse.

Overall and event-free survival were better at 5 years by about 7% to 8% in the experimental arm using midostaurin, she said. Caveats are that complete response rates were similar in both arms and lower than reported in other trials.

“Because we know that patients with this FLT3 mutation have a very poor prognosis with standard chemotherapy, more than half of the patients in this trial received an allogeneic transplant,” Dr. Lee noted. “But the abstract does say that the results are similar if you censor at the time of the transplant.”

In this same vein of precision medicine is plenary abstract 1, testing whether adding rituximab to standard chemotherapy improves outcomes in adults with CD-20–positive, Philadelphia chromosome–negative, B-cell precursor acute lymphoblastic leukemia (ALL). Rituximab (Rituxan) binds to CD-20, which is found in about 30% to 50% of adult B-cell ALL, she said.

At 2 years, patients treated with rituximab had longer event-free survival than controls (65% vs. 52%; P = .038), but similar overall survival (71% vs. 64%; P = .09), according to the abstract. The rituximab arm also received more allogeneic transplants, but again, after censoring the data, the abstract states that both event-free and overall survival were longer with rituximab, Dr. Lee said.

Sickle cell anemia

Sunday’s plenary session will also feature the very important TWiTCH (TCD with Transfusions Changing to Hydroxyurea) study evaluating hydroxyurea therapy as an alternative to chronic blood transfusions to prevent stroke. Stroke is one of the most dreaded complications of sickle cell disease, occurring in up to 10% of children, Dr. Williams said. Though transfusions are effective, they have to be continued indefinitely and lead to iron overload. Hydroxyurea increases the amount of fetal hemoglobin and fetal red blood cells and has become a standard therapy to attenuate the complications of sickle cell.

The phase III noninferiority study, which used Transcranial Doppler (TCD) screening to identify children at elevated risk for stroke, showed that hydroxyurea “was as good as current therapy with red cell transfusions and there was some indication, although not significant, that it might even be superior in lowering the TCD levels,” Dr. Williams said. An added benefit of the hydroxyurea was that it improved the patients’ iron overload status. There were no strokes in either group.

Sunday’s abstract 202 is another presentation “that I’m sure will get a lot of attention,” Dr. Williams said. It offers updated details on outcomes from patients with sickle cell disease (SCD) treated with a novel gene therapy transduced with the LentiGlobin BB305 (Bluebird Bio) lentiviral vector. Patients with beta thalassemia major have remained transfusion-independent for more than a year after this treatment, with results now available from four patients with SCD. One patient with a severe phenotype has had no sickle cell complications and has been able to stop his transfusion therapy, while two of the other four patients are also transfusion-independent.

“This is an early study showing what appears to be efficacy of the gene therapy approach not in thalassemia, but in sickle cell disease,” Dr. Williams said, noting that abstract 3233 will also feature results using LentiGlobin gene therapy in severe SCD.

ASH/EHA joint symposium

Also noteworthy is a special joint ASH/European Hematology Association symposium looking at how well genomic data are being incorporated into practice in the U.S. and Europe.

Monday, Dec. 7

ASH/FDA joint symposium

A joint ASH/FDA symposium on late-breaking drug approvals is new this year and features drugs that gained approval in November 2015. FDA product-reviewers will discuss safety and efficacy issues in the clinical approval trials and toxicity studies, while clinicians will share their experiences in the real-world use of these drugs.

“This is information that is really going to be very hot off the press and presented in conjunction with the FDA,” Dr. Lee said.

Dr. Williams reported research funding from Bluebird Bio. Dr. Lee reported having no conflicts of interest.

[email protected]

FROM A TELECONFERENCE – The American Society of Hematology’s (ASH) 57th annual meeting in Orlando is chock-full of much-anticipated results in cancer immunotherapies such as CAR T cell therapies and checkpoint inhibitors, advances in sickle cell disease, and practical advice on managing the latest drugs in the clinic, ASH officials said in a teleconference. Here are some of the day-by-day picks selected by ASH president Dr. David Williams and ASH secretary Dr. Stephanie J. Lee, who gave their recommendations during a conference call for the press. Meeting abstracts are now available online.

Saturday, Dec. 5

Clinical applications of newly approved drugs

The popular special education session on clinical applications of newly approved drugs returns on Saturday, Dec. 5 at 9:30 a.m., with didactic presentations that address issues clinicians may face such as drug-drug interactions, side effects, and adverse events. The three drugs to be discussed this year are: idarucizumab (Praxbind), the first specific reversal agent approved for dabigatran reversal; blinatumomab (Blincyto), approved for second-line treatment of Philadelphia chromosomenegative acute lymphoblastic leukemia; and the histone deacetylase (HDAC) inhibitor panobinostat (Farydak), approved for the treatment of multiple myeloma.

Adoptive immunotherapy

One presentation to look out for next month is abstract 99at 12:30 p.m. on Saturday, Dec. 5 in the adoptive immunotherapy session, Dr. Williams told reporters. The chimeric antigen receptor (CAR)-T-cell approach has relied on genetically engineering the patient’s own T cells to rev up the immune system. This group’s approach is to treat B-cell malignancies after allogeneic hematopoietic stem cell transplantation using a single infusion of anti-CD19 CAR-T cells from the patient’s transplant donor.

Eight of 20 patients treated with this strategy achieved remission, including six complete remissions and two partial remissions. Importantly, none of these patients developed acute graft-versus-host disease, a potential consequence of using allogeneic rather than autologous T cells, he said. The authors also noted that patients who responded and went into remission were marked by higher numbers of these infused CAR-T cells in their circulation, suggesting a biomarker of response.

Checkpoint, please?

Immunotherapy is a “very hot area,” so ASH has put together a special session at 4 p.m. Saturday called “Checkpoint, Please?” Dr. Williams said. Topics include the role of programmed death (PD)-1 and PD-ligand 1 in acute and chronic graft-versus-host disease, checkpoint blockade with neoantigen cancer vaccines, and insights into the mechanisms of action of anti-CTLA-4 (cytotoxic T-lymphocyte–associated protein 4) antibody therapy.

Sunday, Dec. 6

Precision medicine

Sunday’s plenary scientific session will include several noteworthy personalized medicine abstracts featuring emerging therapies targeted to specific genetic subtypes, Dr. Lee, from the University of Washington, Seattle, said.

Plenary abstract 6 is a large, multinational study looking at whether adding the multikinase inhibitor midostaurin to standard induction therapy and carried through 1 year of maintenance would improve outcomes in newly diagnosed acute myeloid leukemia with FLT3 mutations. Patients with these deleterious mutations do enter remission with chemotherapy, but often relapse.

Overall and event-free survival were better at 5 years by about 7% to 8% in the experimental arm using midostaurin, she said. Caveats are that complete response rates were similar in both arms and lower than reported in other trials.

“Because we know that patients with this FLT3 mutation have a very poor prognosis with standard chemotherapy, more than half of the patients in this trial received an allogeneic transplant,” Dr. Lee noted. “But the abstract does say that the results are similar if you censor at the time of the transplant.”

In this same vein of precision medicine is plenary abstract 1, testing whether adding rituximab to standard chemotherapy improves outcomes in adults with CD-20–positive, Philadelphia chromosome–negative, B-cell precursor acute lymphoblastic leukemia (ALL). Rituximab (Rituxan) binds to CD-20, which is found in about 30% to 50% of adult B-cell ALL, she said.

At 2 years, patients treated with rituximab had longer event-free survival than controls (65% vs. 52%; P = .038), but similar overall survival (71% vs. 64%; P = .09), according to the abstract. The rituximab arm also received more allogeneic transplants, but again, after censoring the data, the abstract states that both event-free and overall survival were longer with rituximab, Dr. Lee said.

Sickle cell anemia

Sunday’s plenary session will also feature the very important TWiTCH (TCD with Transfusions Changing to Hydroxyurea) study evaluating hydroxyurea therapy as an alternative to chronic blood transfusions to prevent stroke. Stroke is one of the most dreaded complications of sickle cell disease, occurring in up to 10% of children, Dr. Williams said. Though transfusions are effective, they have to be continued indefinitely and lead to iron overload. Hydroxyurea increases the amount of fetal hemoglobin and fetal red blood cells and has become a standard therapy to attenuate the complications of sickle cell.

The phase III noninferiority study, which used Transcranial Doppler (TCD) screening to identify children at elevated risk for stroke, showed that hydroxyurea “was as good as current therapy with red cell transfusions and there was some indication, although not significant, that it might even be superior in lowering the TCD levels,” Dr. Williams said. An added benefit of the hydroxyurea was that it improved the patients’ iron overload status. There were no strokes in either group.

Sunday’s abstract 202 is another presentation “that I’m sure will get a lot of attention,” Dr. Williams said. It offers updated details on outcomes from patients with sickle cell disease (SCD) treated with a novel gene therapy transduced with the LentiGlobin BB305 (Bluebird Bio) lentiviral vector. Patients with beta thalassemia major have remained transfusion-independent for more than a year after this treatment, with results now available from four patients with SCD. One patient with a severe phenotype has had no sickle cell complications and has been able to stop his transfusion therapy, while two of the other four patients are also transfusion-independent.

“This is an early study showing what appears to be efficacy of the gene therapy approach not in thalassemia, but in sickle cell disease,” Dr. Williams said, noting that abstract 3233 will also feature results using LentiGlobin gene therapy in severe SCD.

ASH/EHA joint symposium

Also noteworthy is a special joint ASH/European Hematology Association symposium looking at how well genomic data are being incorporated into practice in the U.S. and Europe.

Monday, Dec. 7

ASH/FDA joint symposium

A joint ASH/FDA symposium on late-breaking drug approvals is new this year and features drugs that gained approval in November 2015. FDA product-reviewers will discuss safety and efficacy issues in the clinical approval trials and toxicity studies, while clinicians will share their experiences in the real-world use of these drugs.

“This is information that is really going to be very hot off the press and presented in conjunction with the FDA,” Dr. Lee said.

Dr. Williams reported research funding from Bluebird Bio. Dr. Lee reported having no conflicts of interest.

[email protected]

FROM A TELECONFERENCE – The American Society of Hematology’s (ASH) 57th annual meeting in Orlando is chock-full of much-anticipated results in cancer immunotherapies such as CAR T cell therapies and checkpoint inhibitors, advances in sickle cell disease, and practical advice on managing the latest drugs in the clinic, ASH officials said in a teleconference. Here are some of the day-by-day picks selected by ASH president Dr. David Williams and ASH secretary Dr. Stephanie J. Lee, who gave their recommendations during a conference call for the press. Meeting abstracts are now available online.

Saturday, Dec. 5

Clinical applications of newly approved drugs

The popular special education session on clinical applications of newly approved drugs returns on Saturday, Dec. 5 at 9:30 a.m., with didactic presentations that address issues clinicians may face such as drug-drug interactions, side effects, and adverse events. The three drugs to be discussed this year are: idarucizumab (Praxbind), the first specific reversal agent approved for dabigatran reversal; blinatumomab (Blincyto), approved for second-line treatment of Philadelphia chromosomenegative acute lymphoblastic leukemia; and the histone deacetylase (HDAC) inhibitor panobinostat (Farydak), approved for the treatment of multiple myeloma.

Adoptive immunotherapy

One presentation to look out for next month is abstract 99at 12:30 p.m. on Saturday, Dec. 5 in the adoptive immunotherapy session, Dr. Williams told reporters. The chimeric antigen receptor (CAR)-T-cell approach has relied on genetically engineering the patient’s own T cells to rev up the immune system. This group’s approach is to treat B-cell malignancies after allogeneic hematopoietic stem cell transplantation using a single infusion of anti-CD19 CAR-T cells from the patient’s transplant donor.

Eight of 20 patients treated with this strategy achieved remission, including six complete remissions and two partial remissions. Importantly, none of these patients developed acute graft-versus-host disease, a potential consequence of using allogeneic rather than autologous T cells, he said. The authors also noted that patients who responded and went into remission were marked by higher numbers of these infused CAR-T cells in their circulation, suggesting a biomarker of response.

Checkpoint, please?

Immunotherapy is a “very hot area,” so ASH has put together a special session at 4 p.m. Saturday called “Checkpoint, Please?” Dr. Williams said. Topics include the role of programmed death (PD)-1 and PD-ligand 1 in acute and chronic graft-versus-host disease, checkpoint blockade with neoantigen cancer vaccines, and insights into the mechanisms of action of anti-CTLA-4 (cytotoxic T-lymphocyte–associated protein 4) antibody therapy.

Sunday, Dec. 6

Precision medicine

Sunday’s plenary scientific session will include several noteworthy personalized medicine abstracts featuring emerging therapies targeted to specific genetic subtypes, Dr. Lee, from the University of Washington, Seattle, said.

Plenary abstract 6 is a large, multinational study looking at whether adding the multikinase inhibitor midostaurin to standard induction therapy and carried through 1 year of maintenance would improve outcomes in newly diagnosed acute myeloid leukemia with FLT3 mutations. Patients with these deleterious mutations do enter remission with chemotherapy, but often relapse.

Overall and event-free survival were better at 5 years by about 7% to 8% in the experimental arm using midostaurin, she said. Caveats are that complete response rates were similar in both arms and lower than reported in other trials.

“Because we know that patients with this FLT3 mutation have a very poor prognosis with standard chemotherapy, more than half of the patients in this trial received an allogeneic transplant,” Dr. Lee noted. “But the abstract does say that the results are similar if you censor at the time of the transplant.”

In this same vein of precision medicine is plenary abstract 1, testing whether adding rituximab to standard chemotherapy improves outcomes in adults with CD-20–positive, Philadelphia chromosome–negative, B-cell precursor acute lymphoblastic leukemia (ALL). Rituximab (Rituxan) binds to CD-20, which is found in about 30% to 50% of adult B-cell ALL, she said.

At 2 years, patients treated with rituximab had longer event-free survival than controls (65% vs. 52%; P = .038), but similar overall survival (71% vs. 64%; P = .09), according to the abstract. The rituximab arm also received more allogeneic transplants, but again, after censoring the data, the abstract states that both event-free and overall survival were longer with rituximab, Dr. Lee said.

Sickle cell anemia

Sunday’s plenary session will also feature the very important TWiTCH (TCD with Transfusions Changing to Hydroxyurea) study evaluating hydroxyurea therapy as an alternative to chronic blood transfusions to prevent stroke. Stroke is one of the most dreaded complications of sickle cell disease, occurring in up to 10% of children, Dr. Williams said. Though transfusions are effective, they have to be continued indefinitely and lead to iron overload. Hydroxyurea increases the amount of fetal hemoglobin and fetal red blood cells and has become a standard therapy to attenuate the complications of sickle cell.

The phase III noninferiority study, which used Transcranial Doppler (TCD) screening to identify children at elevated risk for stroke, showed that hydroxyurea “was as good as current therapy with red cell transfusions and there was some indication, although not significant, that it might even be superior in lowering the TCD levels,” Dr. Williams said. An added benefit of the hydroxyurea was that it improved the patients’ iron overload status. There were no strokes in either group.

Sunday’s abstract 202 is another presentation “that I’m sure will get a lot of attention,” Dr. Williams said. It offers updated details on outcomes from patients with sickle cell disease (SCD) treated with a novel gene therapy transduced with the LentiGlobin BB305 (Bluebird Bio) lentiviral vector. Patients with beta thalassemia major have remained transfusion-independent for more than a year after this treatment, with results now available from four patients with SCD. One patient with a severe phenotype has had no sickle cell complications and has been able to stop his transfusion therapy, while two of the other four patients are also transfusion-independent.

“This is an early study showing what appears to be efficacy of the gene therapy approach not in thalassemia, but in sickle cell disease,” Dr. Williams said, noting that abstract 3233 will also feature results using LentiGlobin gene therapy in severe SCD.

ASH/EHA joint symposium

Also noteworthy is a special joint ASH/European Hematology Association symposium looking at how well genomic data are being incorporated into practice in the U.S. and Europe.

Monday, Dec. 7

ASH/FDA joint symposium

A joint ASH/FDA symposium on late-breaking drug approvals is new this year and features drugs that gained approval in November 2015. FDA product-reviewers will discuss safety and efficacy issues in the clinical approval trials and toxicity studies, while clinicians will share their experiences in the real-world use of these drugs.

“This is information that is really going to be very hot off the press and presented in conjunction with the FDA,” Dr. Lee said.

Dr. Williams reported research funding from Bluebird Bio. Dr. Lee reported having no conflicts of interest.

[email protected]

Iron pills

A new study suggests it may be difficult for the body to absorb iron in the necessary or desired quantities when iron supplements are administered in 24-hour intervals.

Investigators believe this is due to hepcidin. They found that giving subjects iron supplements at doses of 60 mg or higher increased hepcidin levels for up to 24 hours and was associated with lower iron absorption on the following day.

The team postulated that administering low-dose iron on alternate days may overcome this problem, but they said more research is needed to confirm this.

The investigators reported their findings in Blood.

Diego Moretti, PhD, of the Swiss Federal Institute of Technology Zürich, and his colleagues conducted this study in 54 young women.

The women had depleted iron reserves but were not yet anemic (plasma ferritin ≤20 mcg/L). They received a daily dose of at least 40 mg of iron, as is commonly prescribed in cases of iron deficiency.

Afterward, the investigators measured how the hepcidin concentration developed and quantified its effect on the absorption of subsequent doses of iron.

To analyze iron reabsorption, the team used stable iron isotopes as indicator substances. These substances have a modified ratio of stable iron isotopes. Iron-56 is the most frequent naturally occurring stable iron isotope (91.7%), followed by iron-54 (5.8%), and iron-57 (2.1%). Iron-58 occurs only in trace amounts.

The investigators used tablets with increased quantities of iron-57, iron-54, and iron-58. And they were able to measure endogenous iron absorption by observing isotope ratio changes within the body.

The team found that hepcidin reached its peak concentration after 6 to 8 hours, but even 24 hours after the first dose of iron, it was still present in high enough quantities to markedly reduce absorption of the second dose.

The body was only partly able to absorb a second dose of iron, which was given either on the same day or 24 hours after the first dose.

“To improve the percentage of iron absorbed, it would likely be more efficient to wait longer between doses,” Dr Moretti said.

However, he noted that more research is needed to confirm this, particularly because this study had 2 limitations. The first is that participants were all healthy young women without anemia, and the second is that iron absorption was observed over 2 days only.

The investigators are now preparing to conduct a follow-up study to analyze hepcidin concentration over the course of an iron supplementation regimen lasting several weeks.

Iron pills

A new study suggests it may be difficult for the body to absorb iron in the necessary or desired quantities when iron supplements are administered in 24-hour intervals.

Investigators believe this is due to hepcidin. They found that giving subjects iron supplements at doses of 60 mg or higher increased hepcidin levels for up to 24 hours and was associated with lower iron absorption on the following day.

The team postulated that administering low-dose iron on alternate days may overcome this problem, but they said more research is needed to confirm this.

The investigators reported their findings in Blood.

Diego Moretti, PhD, of the Swiss Federal Institute of Technology Zürich, and his colleagues conducted this study in 54 young women.

The women had depleted iron reserves but were not yet anemic (plasma ferritin ≤20 mcg/L). They received a daily dose of at least 40 mg of iron, as is commonly prescribed in cases of iron deficiency.

Afterward, the investigators measured how the hepcidin concentration developed and quantified its effect on the absorption of subsequent doses of iron.

To analyze iron reabsorption, the team used stable iron isotopes as indicator substances. These substances have a modified ratio of stable iron isotopes. Iron-56 is the most frequent naturally occurring stable iron isotope (91.7%), followed by iron-54 (5.8%), and iron-57 (2.1%). Iron-58 occurs only in trace amounts.

The investigators used tablets with increased quantities of iron-57, iron-54, and iron-58. And they were able to measure endogenous iron absorption by observing isotope ratio changes within the body.

The team found that hepcidin reached its peak concentration after 6 to 8 hours, but even 24 hours after the first dose of iron, it was still present in high enough quantities to markedly reduce absorption of the second dose.

The body was only partly able to absorb a second dose of iron, which was given either on the same day or 24 hours after the first dose.

“To improve the percentage of iron absorbed, it would likely be more efficient to wait longer between doses,” Dr Moretti said.

However, he noted that more research is needed to confirm this, particularly because this study had 2 limitations. The first is that participants were all healthy young women without anemia, and the second is that iron absorption was observed over 2 days only.

The investigators are now preparing to conduct a follow-up study to analyze hepcidin concentration over the course of an iron supplementation regimen lasting several weeks.

Iron pills

A new study suggests it may be difficult for the body to absorb iron in the necessary or desired quantities when iron supplements are administered in 24-hour intervals.

Investigators believe this is due to hepcidin. They found that giving subjects iron supplements at doses of 60 mg or higher increased hepcidin levels for up to 24 hours and was associated with lower iron absorption on the following day.

The team postulated that administering low-dose iron on alternate days may overcome this problem, but they said more research is needed to confirm this.

The investigators reported their findings in Blood.

Diego Moretti, PhD, of the Swiss Federal Institute of Technology Zürich, and his colleagues conducted this study in 54 young women.

The women had depleted iron reserves but were not yet anemic (plasma ferritin ≤20 mcg/L). They received a daily dose of at least 40 mg of iron, as is commonly prescribed in cases of iron deficiency.

Afterward, the investigators measured how the hepcidin concentration developed and quantified its effect on the absorption of subsequent doses of iron.

To analyze iron reabsorption, the team used stable iron isotopes as indicator substances. These substances have a modified ratio of stable iron isotopes. Iron-56 is the most frequent naturally occurring stable iron isotope (91.7%), followed by iron-54 (5.8%), and iron-57 (2.1%). Iron-58 occurs only in trace amounts.

The investigators used tablets with increased quantities of iron-57, iron-54, and iron-58. And they were able to measure endogenous iron absorption by observing isotope ratio changes within the body.

The team found that hepcidin reached its peak concentration after 6 to 8 hours, but even 24 hours after the first dose of iron, it was still present in high enough quantities to markedly reduce absorption of the second dose.

The body was only partly able to absorb a second dose of iron, which was given either on the same day or 24 hours after the first dose.

“To improve the percentage of iron absorbed, it would likely be more efficient to wait longer between doses,” Dr Moretti said.

However, he noted that more research is needed to confirm this, particularly because this study had 2 limitations. The first is that participants were all healthy young women without anemia, and the second is that iron absorption was observed over 2 days only.

The investigators are now preparing to conduct a follow-up study to analyze hepcidin concentration over the course of an iron supplementation regimen lasting several weeks.

Thomas J. Braciale, MD, PhD

Photo courtesy of

Josh Barney/University of

Virginia Health System

An unexpected result of a lab experiment has led researchers to a new way to trigger red blood cell (RBC) production.

They found that engaging a stress receptor on type 1 conventional dendritic cells can induce stress erythropoiesis in mice.

The team believes that, eventually, this method could be used to turn on RBC production in humans when necessary, perhaps to replace a blood transfusion or as a stop-gap measure when a transfusion is delayed.

Thomas J. Braciale, MD, PhD, of the University of Virginia in Charlottesville, and his colleagues conducted this research and reported the results in The Journal of Clinical Investigation.

The team was not investigating RBC production when they made their discovery. They were looking into the role of dendritic cells in the lungs.

Dendritic cells have traditionally been thought to be sensors of infection and inflammation, but a lab test involving the flu virus produced an unexpected effect in mice that ultimately revealed a new aspect to the cells’ function.

The researchers injected mice with the flu virus and an αCD24 monoclonal antibody, which resulted in splenomegaly. The team was baffled at this outcome, so they repeated the experiment, only to get the same results.

“We did it again, and I didn’t believe it, and we did it again, and I didn’t believe it,” Dr Braciale recalled. “I asked whether you needed flu to infect the mice when you injected this antibody. So the postdoc did the experiment, and he just injected the antibody without flu-injecting the mice—giant spleens. After much consultation, after talking with my colleagues in pathology, we decided we were inducing stress erythropoiesis.”

Specifically, the researchers found that engaging CD24 on type 1 conventional dendritic cells upregulates expression of the Kit ligand stem cell factor, which results in Kit-mediated proliferative expansion of early erythroid progenitors and transient reticulocytosis.

“In a very basic way, what we’ve discovered is that the process of regulating stress in the body is mediated—certainly in part, at least—by these dendritic cells,” Dr Braciale explained. “And stress can be a variety of different stresses.”

“It doesn’t have to be infection. It doesn’t have to be inflammation. It can be anemia. It can be hemorrhage. And these cells act to initiate this response that, until this report, there’s been really no evidence that [dendritic] cells ever participate in making red blood cells.”

More work is needed before this approach to RBC production can be tested in humans. However, Dr Braciale is optimistic, based on the findings so far.

“We’re very excited to see where this goes,” he said. “We know that the same things can be done in humans in the following sense. There are mice called humanized mice. These are mice that are engineered so they have a human blood system. And if you inject these mice with this antibody, they’ll make red blood cells.”

Thomas J. Braciale, MD, PhD

Photo courtesy of

Josh Barney/University of

Virginia Health System

An unexpected result of a lab experiment has led researchers to a new way to trigger red blood cell (RBC) production.

They found that engaging a stress receptor on type 1 conventional dendritic cells can induce stress erythropoiesis in mice.

The team believes that, eventually, this method could be used to turn on RBC production in humans when necessary, perhaps to replace a blood transfusion or as a stop-gap measure when a transfusion is delayed.

Thomas J. Braciale, MD, PhD, of the University of Virginia in Charlottesville, and his colleagues conducted this research and reported the results in The Journal of Clinical Investigation.

The team was not investigating RBC production when they made their discovery. They were looking into the role of dendritic cells in the lungs.

Dendritic cells have traditionally been thought to be sensors of infection and inflammation, but a lab test involving the flu virus produced an unexpected effect in mice that ultimately revealed a new aspect to the cells’ function.

The researchers injected mice with the flu virus and an αCD24 monoclonal antibody, which resulted in splenomegaly. The team was baffled at this outcome, so they repeated the experiment, only to get the same results.

“We did it again, and I didn’t believe it, and we did it again, and I didn’t believe it,” Dr Braciale recalled. “I asked whether you needed flu to infect the mice when you injected this antibody. So the postdoc did the experiment, and he just injected the antibody without flu-injecting the mice—giant spleens. After much consultation, after talking with my colleagues in pathology, we decided we were inducing stress erythropoiesis.”

Specifically, the researchers found that engaging CD24 on type 1 conventional dendritic cells upregulates expression of the Kit ligand stem cell factor, which results in Kit-mediated proliferative expansion of early erythroid progenitors and transient reticulocytosis.

“In a very basic way, what we’ve discovered is that the process of regulating stress in the body is mediated—certainly in part, at least—by these dendritic cells,” Dr Braciale explained. “And stress can be a variety of different stresses.”

“It doesn’t have to be infection. It doesn’t have to be inflammation. It can be anemia. It can be hemorrhage. And these cells act to initiate this response that, until this report, there’s been really no evidence that [dendritic] cells ever participate in making red blood cells.”

More work is needed before this approach to RBC production can be tested in humans. However, Dr Braciale is optimistic, based on the findings so far.

“We’re very excited to see where this goes,” he said. “We know that the same things can be done in humans in the following sense. There are mice called humanized mice. These are mice that are engineered so they have a human blood system. And if you inject these mice with this antibody, they’ll make red blood cells.”

Thomas J. Braciale, MD, PhD

Photo courtesy of

Josh Barney/University of

Virginia Health System

An unexpected result of a lab experiment has led researchers to a new way to trigger red blood cell (RBC) production.

They found that engaging a stress receptor on type 1 conventional dendritic cells can induce stress erythropoiesis in mice.

The team believes that, eventually, this method could be used to turn on RBC production in humans when necessary, perhaps to replace a blood transfusion or as a stop-gap measure when a transfusion is delayed.

Thomas J. Braciale, MD, PhD, of the University of Virginia in Charlottesville, and his colleagues conducted this research and reported the results in The Journal of Clinical Investigation.

The team was not investigating RBC production when they made their discovery. They were looking into the role of dendritic cells in the lungs.

Dendritic cells have traditionally been thought to be sensors of infection and inflammation, but a lab test involving the flu virus produced an unexpected effect in mice that ultimately revealed a new aspect to the cells’ function.

The researchers injected mice with the flu virus and an αCD24 monoclonal antibody, which resulted in splenomegaly. The team was baffled at this outcome, so they repeated the experiment, only to get the same results.

“We did it again, and I didn’t believe it, and we did it again, and I didn’t believe it,” Dr Braciale recalled. “I asked whether you needed flu to infect the mice when you injected this antibody. So the postdoc did the experiment, and he just injected the antibody without flu-injecting the mice—giant spleens. After much consultation, after talking with my colleagues in pathology, we decided we were inducing stress erythropoiesis.”

Specifically, the researchers found that engaging CD24 on type 1 conventional dendritic cells upregulates expression of the Kit ligand stem cell factor, which results in Kit-mediated proliferative expansion of early erythroid progenitors and transient reticulocytosis.

“In a very basic way, what we’ve discovered is that the process of regulating stress in the body is mediated—certainly in part, at least—by these dendritic cells,” Dr Braciale explained. “And stress can be a variety of different stresses.”

“It doesn’t have to be infection. It doesn’t have to be inflammation. It can be anemia. It can be hemorrhage. And these cells act to initiate this response that, until this report, there’s been really no evidence that [dendritic] cells ever participate in making red blood cells.”

More work is needed before this approach to RBC production can be tested in humans. However, Dr Braciale is optimistic, based on the findings so far.

“We’re very excited to see where this goes,” he said. “We know that the same things can be done in humans in the following sense. There are mice called humanized mice. These are mice that are engineered so they have a human blood system. And if you inject these mice with this antibody, they’ll make red blood cells.”