Hematologic Malignancies

The Food and Drug Administration has issued a safety alert warning against long-term use of azithromycin to prevent bronchiolitis obliterans syndrome in patients with blood or lymph node cancers who have received donor stem cell transplants.

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The Food and Drug Administration has issued a safety alert warning against long-term use of azithromycin to prevent bronchiolitis obliterans syndrome in patients with blood or lymph node cancers who have received donor stem cell transplants.

[email protected]

The Food and Drug Administration has issued a safety alert warning against long-term use of azithromycin to prevent bronchiolitis obliterans syndrome in patients with blood or lymph node cancers who have received donor stem cell transplants.

[email protected]

With the help of gene expression signatures, a simulated treatment learning model identified which patients with multiple myeloma would benefit most from treatment with bortezomib or lenalidomide, researchers reported in Nature Communications.

The study included 910 participants across three phase 3 trials. In all, 20% would have a 100% greater-than-average progression-free survival (PFS) benefit from bortezomib, while 31% would have a 200% greater-than-average PFS benefit from lenalidomide, wrote Joske Ubels of University Center Utrecht, the Netherlands, and her colleagues.

The genetic heterogeneity of cancer and risk of treatment necessitate tools that “predict – at the moment of diagnosis – which patients will benefit most from a certain treatment,” the researchers wrote. While gene expression signatures can predict a favorable or adverse prognosis, they do not account for the effect of treatment on survival.

“The key idea of simulated treatment learning is that a patient’s treatment benefit can be estimated by comparing [his or her] survival to a set of genetically similar patients [who] received the comparator treatment,” they noted.

To do so, the researchers applied an algorithm called GESTURE to combined data from the TT2 (Total Therapy 2 for Multiple Myeloma), TT3, and HOVON-65/GMMG-HD4 trials. These trials compared bortezomib or lenalidomide with conventional therapies for multiple myeloma. The model identified 180 patients (20%) for whom bortezomib would produce a 100% greater PFS benefit than in the study population as a whole. Conversely, lenalidomide would produce a 200% greater PFS benefit in 31% of patients.

The simulated treatment learning model “can derive clinically actionable gene expression signatures that enable a more personalized approach to treatment,” the researchers concluded. The method requires a large dataset but could be useful for trials that have missed their primary endpoint, such as the CheckMate-026 trial of nivolumab. The next step is to see if the model makes useful treatment predictions for other cancers. The code needed to train and validate the model is available at github.com/jubels/GESTURE.

The Van Herk Fellowship provided support. The lenalidomide dataset was created as part of the Multiple Myeloma Research Foundation Personalized Medicine Initiative. Dr. Ubels and one coinvestigator are employees of SkylineDx; another coinvestigator served on its advisory board. The others reported having no relevant conflicts of interest.

SOURCE: Ubels J et al. Nat Commun. 2018 Jul 27. doi: 10.1038/s41467-018-05348-5.

With the help of gene expression signatures, a simulated treatment learning model identified which patients with multiple myeloma would benefit most from treatment with bortezomib or lenalidomide, researchers reported in Nature Communications.

The study included 910 participants across three phase 3 trials. In all, 20% would have a 100% greater-than-average progression-free survival (PFS) benefit from bortezomib, while 31% would have a 200% greater-than-average PFS benefit from lenalidomide, wrote Joske Ubels of University Center Utrecht, the Netherlands, and her colleagues.

The genetic heterogeneity of cancer and risk of treatment necessitate tools that “predict – at the moment of diagnosis – which patients will benefit most from a certain treatment,” the researchers wrote. While gene expression signatures can predict a favorable or adverse prognosis, they do not account for the effect of treatment on survival.

“The key idea of simulated treatment learning is that a patient’s treatment benefit can be estimated by comparing [his or her] survival to a set of genetically similar patients [who] received the comparator treatment,” they noted.

To do so, the researchers applied an algorithm called GESTURE to combined data from the TT2 (Total Therapy 2 for Multiple Myeloma), TT3, and HOVON-65/GMMG-HD4 trials. These trials compared bortezomib or lenalidomide with conventional therapies for multiple myeloma. The model identified 180 patients (20%) for whom bortezomib would produce a 100% greater PFS benefit than in the study population as a whole. Conversely, lenalidomide would produce a 200% greater PFS benefit in 31% of patients.

The simulated treatment learning model “can derive clinically actionable gene expression signatures that enable a more personalized approach to treatment,” the researchers concluded. The method requires a large dataset but could be useful for trials that have missed their primary endpoint, such as the CheckMate-026 trial of nivolumab. The next step is to see if the model makes useful treatment predictions for other cancers. The code needed to train and validate the model is available at github.com/jubels/GESTURE.

The Van Herk Fellowship provided support. The lenalidomide dataset was created as part of the Multiple Myeloma Research Foundation Personalized Medicine Initiative. Dr. Ubels and one coinvestigator are employees of SkylineDx; another coinvestigator served on its advisory board. The others reported having no relevant conflicts of interest.

SOURCE: Ubels J et al. Nat Commun. 2018 Jul 27. doi: 10.1038/s41467-018-05348-5.

With the help of gene expression signatures, a simulated treatment learning model identified which patients with multiple myeloma would benefit most from treatment with bortezomib or lenalidomide, researchers reported in Nature Communications.

The study included 910 participants across three phase 3 trials. In all, 20% would have a 100% greater-than-average progression-free survival (PFS) benefit from bortezomib, while 31% would have a 200% greater-than-average PFS benefit from lenalidomide, wrote Joske Ubels of University Center Utrecht, the Netherlands, and her colleagues.

The genetic heterogeneity of cancer and risk of treatment necessitate tools that “predict – at the moment of diagnosis – which patients will benefit most from a certain treatment,” the researchers wrote. While gene expression signatures can predict a favorable or adverse prognosis, they do not account for the effect of treatment on survival.

“The key idea of simulated treatment learning is that a patient’s treatment benefit can be estimated by comparing [his or her] survival to a set of genetically similar patients [who] received the comparator treatment,” they noted.

To do so, the researchers applied an algorithm called GESTURE to combined data from the TT2 (Total Therapy 2 for Multiple Myeloma), TT3, and HOVON-65/GMMG-HD4 trials. These trials compared bortezomib or lenalidomide with conventional therapies for multiple myeloma. The model identified 180 patients (20%) for whom bortezomib would produce a 100% greater PFS benefit than in the study population as a whole. Conversely, lenalidomide would produce a 200% greater PFS benefit in 31% of patients.

The simulated treatment learning model “can derive clinically actionable gene expression signatures that enable a more personalized approach to treatment,” the researchers concluded. The method requires a large dataset but could be useful for trials that have missed their primary endpoint, such as the CheckMate-026 trial of nivolumab. The next step is to see if the model makes useful treatment predictions for other cancers. The code needed to train and validate the model is available at github.com/jubels/GESTURE.

The Van Herk Fellowship provided support. The lenalidomide dataset was created as part of the Multiple Myeloma Research Foundation Personalized Medicine Initiative. Dr. Ubels and one coinvestigator are employees of SkylineDx; another coinvestigator served on its advisory board. The others reported having no relevant conflicts of interest.

SOURCE: Ubels J et al. Nat Commun. 2018 Jul 27. doi: 10.1038/s41467-018-05348-5.

Physicians from Menoufia University and Cairo University in Egypt, and Al Hada Armed Forces Hospital in Saudi Arabia report on a patient who developed myelodysplasia with excess blasts 1 year after he started on the tumor necrosis factor-alpha blocker etanercept for psoriasis. The patient, a 76-year-old man, arrived at the emergency department (ED) with ecchymosis and recurrent epistaxis. He had a critically low platelet count, anemia, and normal leukocyte count. The reticulocyte index, serum ferritin, and folate levels indicated ineffective erythropoiesis. Bone marrow aspirate and biopsy confirmed a diagnosis of myelodysplastic syndrome.

The physicians stopped the etanercept and administered 2 cycles of azacitidine and folic acid supplementation, but the response was minima,l and the patient platelet count worsened. While waiting for the third cycle, the patient was readmitted to the ED with lower gastrointestinal bleeding, epistaxis, and shock. He died of cardiopulmonary arrest.

The physicians note that immune dysregulation and altered T-cell hemostasis are essential to the development of myelodysplastic syndrome. They also note that nonspecific activation and proliferation of T lymphocytes has been documented as promoting epidermal growth in genetically susceptible psoriasis patients.

Myelodysplastic syndrome has been associated with psoriasis in about 7% of cases, and researchers have found a higher incidence of leukemia and laryngeal cancer in families of psoriasis patients. There also have been reports of leukemia in psoriasis patients on systemic immunosuppressives. Etanercept has various hematologic adverse effects, including pancytopenia and aplastic anemia.

However, only 4 cases (including this one) have been reported of myelodysplastic syndrome in psoriasis patients. Taken together, the cases add to the growing evidence that suggests a link between myelodysplastic syndrome and etanercept treatment for psoriasis. Those patients, the physicians caution, should be considered at dual risk from treatment and disease. The physicians also recommend regular routine blood counts and discontinuing etanercept at onset of any cytopenias.

Source:
Dawoud NM, Ayoub OH, Essa ES, Dawoud DM. Indian J Dermatol Venereol Leprol. 2018;84(4):463-465.
doi: 10.4103/ijdvl.IJDVL_463_17

Physicians from Menoufia University and Cairo University in Egypt, and Al Hada Armed Forces Hospital in Saudi Arabia report on a patient who developed myelodysplasia with excess blasts 1 year after he started on the tumor necrosis factor-alpha blocker etanercept for psoriasis. The patient, a 76-year-old man, arrived at the emergency department (ED) with ecchymosis and recurrent epistaxis. He had a critically low platelet count, anemia, and normal leukocyte count. The reticulocyte index, serum ferritin, and folate levels indicated ineffective erythropoiesis. Bone marrow aspirate and biopsy confirmed a diagnosis of myelodysplastic syndrome.

The physicians stopped the etanercept and administered 2 cycles of azacitidine and folic acid supplementation, but the response was minima,l and the patient platelet count worsened. While waiting for the third cycle, the patient was readmitted to the ED with lower gastrointestinal bleeding, epistaxis, and shock. He died of cardiopulmonary arrest.

The physicians note that immune dysregulation and altered T-cell hemostasis are essential to the development of myelodysplastic syndrome. They also note that nonspecific activation and proliferation of T lymphocytes has been documented as promoting epidermal growth in genetically susceptible psoriasis patients.

Myelodysplastic syndrome has been associated with psoriasis in about 7% of cases, and researchers have found a higher incidence of leukemia and laryngeal cancer in families of psoriasis patients. There also have been reports of leukemia in psoriasis patients on systemic immunosuppressives. Etanercept has various hematologic adverse effects, including pancytopenia and aplastic anemia.

However, only 4 cases (including this one) have been reported of myelodysplastic syndrome in psoriasis patients. Taken together, the cases add to the growing evidence that suggests a link between myelodysplastic syndrome and etanercept treatment for psoriasis. Those patients, the physicians caution, should be considered at dual risk from treatment and disease. The physicians also recommend regular routine blood counts and discontinuing etanercept at onset of any cytopenias.

Source:
Dawoud NM, Ayoub OH, Essa ES, Dawoud DM. Indian J Dermatol Venereol Leprol. 2018;84(4):463-465.
doi: 10.4103/ijdvl.IJDVL_463_17

Physicians from Menoufia University and Cairo University in Egypt, and Al Hada Armed Forces Hospital in Saudi Arabia report on a patient who developed myelodysplasia with excess blasts 1 year after he started on the tumor necrosis factor-alpha blocker etanercept for psoriasis. The patient, a 76-year-old man, arrived at the emergency department (ED) with ecchymosis and recurrent epistaxis. He had a critically low platelet count, anemia, and normal leukocyte count. The reticulocyte index, serum ferritin, and folate levels indicated ineffective erythropoiesis. Bone marrow aspirate and biopsy confirmed a diagnosis of myelodysplastic syndrome.

The physicians stopped the etanercept and administered 2 cycles of azacitidine and folic acid supplementation, but the response was minima,l and the patient platelet count worsened. While waiting for the third cycle, the patient was readmitted to the ED with lower gastrointestinal bleeding, epistaxis, and shock. He died of cardiopulmonary arrest.

The physicians note that immune dysregulation and altered T-cell hemostasis are essential to the development of myelodysplastic syndrome. They also note that nonspecific activation and proliferation of T lymphocytes has been documented as promoting epidermal growth in genetically susceptible psoriasis patients.

Myelodysplastic syndrome has been associated with psoriasis in about 7% of cases, and researchers have found a higher incidence of leukemia and laryngeal cancer in families of psoriasis patients. There also have been reports of leukemia in psoriasis patients on systemic immunosuppressives. Etanercept has various hematologic adverse effects, including pancytopenia and aplastic anemia.

However, only 4 cases (including this one) have been reported of myelodysplastic syndrome in psoriasis patients. Taken together, the cases add to the growing evidence that suggests a link between myelodysplastic syndrome and etanercept treatment for psoriasis. Those patients, the physicians caution, should be considered at dual risk from treatment and disease. The physicians also recommend regular routine blood counts and discontinuing etanercept at onset of any cytopenias.

Source:
Dawoud NM, Ayoub OH, Essa ES, Dawoud DM. Indian J Dermatol Venereol Leprol. 2018;84(4):463-465.
doi: 10.4103/ijdvl.IJDVL_463_17

A new index of frailty predicts survival in older patients with multiple myeloma based on accumulation of aging-associated deficits, rather than chronological age alone, investigators report. A 16% increased risk of death was seen for each 10% increase in the deficit-accumulation frailty index (DAFI), which includes 25 variables related health, function, and activities of daily living.

There was only a weak correlation between chronological age and increase in deficits tracked by the index, in contrast to a cohort without cancer, in which age and frailty were strongly correlated, the investigators reported in JCO Clinical Cancer Informatics.

“Our results demonstrate that, for patients with multiple myeloma, chronological age alone is not a good measure for assessing overall health,” study author Tanya M. Wildes, MD, of Washington University, St. Louis, said in a news release from the American Society of Clinical Oncology.

Existing tools to assess frailty include an index proposed by the International Myeloma Working Group that looks at age plus other indexes related to comorbidities and activities of daily living, and the revised Myeloma Comorbidity Index that incorporates age with other prognostic factors.

“Although both tools provide prognostic information, chronological age automatically increases frailty without taking biologic or functional age into account,” Dr. Wildes and her coauthors wrote in their report.

By contrast, the DAFI is based on the concept of biologic age, in which the health status of an individual is measured based on the proportion of aging-associated deficits they have accumulated, according to the authors.

To create the DAFI, Dr. Wildes and her colleagues analyzed nearly 2.7 million records of noncancer patients aged 66 years or older in the SEER Medicare Health Outcomes Survey (MHOS) database. They identified 25 variables in the database representing chronic health conditions, activities of daily living, functioning, mental health, and general health.

An individual’s DAFI score was calculated as the sum of scores for each of the 25 variables as 0 for absent, 0.5 for limited, and 1 for present. Predicted DAFI means were calculated for each year of age and used to create age-specific cut points to determine whether an individual would be considered frail or not versus others of the same age.

“In other words, the same frailty score may qualify an 80-year-old individual as fit and a 70-year-old as frail, depending on the cutoff for their respective age group,” investigators explained in their report.

They applied the index to 305 patients with newly diagnosed myeloma in the SEER-MHOS database who were 66 years of age or older (median age, 76 years) and had completed the survey within 1 year of diagnosis.

The DAFI classified 52% of the myeloma patients as frail, and for that group, median overall survival was 26.8 months, versus 43.7 months for nonfrail patients (P = .015), according to the reported data. For each 10% increase in score, the risk of death increased by 16% (P less than .001).

Notably, advancing age was very weakly correlated with increased age-related deficits in the myeloma cohort (r2 = 0.15; P = .010), according to investigators, but very strongly correlated with deficits in the cohort of noncancer patients (r2 = 0.98; P less than .001).

“This suggests that, in patients with multiple myeloma, the prevalence of impairments across domains of function, chronic comorbidities, general health, and mental health are more related to the overall burden of myeloma rather than chronological age alone,” the investigators wrote.

The information used to calculate a DAFI score is easily obtainable during a clinic visit, according to the authors, who provided an overview of all 25 variables in the journal article.

Further development of a computerized program would further enhance usability in the clinic, allowing for real-time calculation during a patient visit, they said.

Survivorship expert Merry Jennifer Markham, MD, said in the ASCO news release that this frailty index is notable because it accounts for more than just chronological age. “Knowing this information can help oncologists have more informed discussions with patients about their prognosis, which in turn can empower patients and families as they weigh treatment options,” she said.

The research was supported by National Cancer Institute. Dr. Wildes reported honoraria from Carevive Systems and research funding from Janssen Oncology. Another coauthor reported honoraria from Celgene and Janssen, and a consulting or advisory role with Amgen and Takeda.

 

SOURCE: Mian HS et al. JCO Clin Cancer Inform. 2018 Jul 25. 2018 Jul 25. doi: 10.1200/CCI.18.00043.

A new index of frailty predicts survival in older patients with multiple myeloma based on accumulation of aging-associated deficits, rather than chronological age alone, investigators report. A 16% increased risk of death was seen for each 10% increase in the deficit-accumulation frailty index (DAFI), which includes 25 variables related health, function, and activities of daily living.

There was only a weak correlation between chronological age and increase in deficits tracked by the index, in contrast to a cohort without cancer, in which age and frailty were strongly correlated, the investigators reported in JCO Clinical Cancer Informatics.

“Our results demonstrate that, for patients with multiple myeloma, chronological age alone is not a good measure for assessing overall health,” study author Tanya M. Wildes, MD, of Washington University, St. Louis, said in a news release from the American Society of Clinical Oncology.

Existing tools to assess frailty include an index proposed by the International Myeloma Working Group that looks at age plus other indexes related to comorbidities and activities of daily living, and the revised Myeloma Comorbidity Index that incorporates age with other prognostic factors.

“Although both tools provide prognostic information, chronological age automatically increases frailty without taking biologic or functional age into account,” Dr. Wildes and her coauthors wrote in their report.

By contrast, the DAFI is based on the concept of biologic age, in which the health status of an individual is measured based on the proportion of aging-associated deficits they have accumulated, according to the authors.

To create the DAFI, Dr. Wildes and her colleagues analyzed nearly 2.7 million records of noncancer patients aged 66 years or older in the SEER Medicare Health Outcomes Survey (MHOS) database. They identified 25 variables in the database representing chronic health conditions, activities of daily living, functioning, mental health, and general health.

An individual’s DAFI score was calculated as the sum of scores for each of the 25 variables as 0 for absent, 0.5 for limited, and 1 for present. Predicted DAFI means were calculated for each year of age and used to create age-specific cut points to determine whether an individual would be considered frail or not versus others of the same age.

“In other words, the same frailty score may qualify an 80-year-old individual as fit and a 70-year-old as frail, depending on the cutoff for their respective age group,” investigators explained in their report.

They applied the index to 305 patients with newly diagnosed myeloma in the SEER-MHOS database who were 66 years of age or older (median age, 76 years) and had completed the survey within 1 year of diagnosis.

The DAFI classified 52% of the myeloma patients as frail, and for that group, median overall survival was 26.8 months, versus 43.7 months for nonfrail patients (P = .015), according to the reported data. For each 10% increase in score, the risk of death increased by 16% (P less than .001).

Notably, advancing age was very weakly correlated with increased age-related deficits in the myeloma cohort (r2 = 0.15; P = .010), according to investigators, but very strongly correlated with deficits in the cohort of noncancer patients (r2 = 0.98; P less than .001).

“This suggests that, in patients with multiple myeloma, the prevalence of impairments across domains of function, chronic comorbidities, general health, and mental health are more related to the overall burden of myeloma rather than chronological age alone,” the investigators wrote.

The information used to calculate a DAFI score is easily obtainable during a clinic visit, according to the authors, who provided an overview of all 25 variables in the journal article.

Further development of a computerized program would further enhance usability in the clinic, allowing for real-time calculation during a patient visit, they said.

Survivorship expert Merry Jennifer Markham, MD, said in the ASCO news release that this frailty index is notable because it accounts for more than just chronological age. “Knowing this information can help oncologists have more informed discussions with patients about their prognosis, which in turn can empower patients and families as they weigh treatment options,” she said.

The research was supported by National Cancer Institute. Dr. Wildes reported honoraria from Carevive Systems and research funding from Janssen Oncology. Another coauthor reported honoraria from Celgene and Janssen, and a consulting or advisory role with Amgen and Takeda.

 

SOURCE: Mian HS et al. JCO Clin Cancer Inform. 2018 Jul 25. 2018 Jul 25. doi: 10.1200/CCI.18.00043.

A new index of frailty predicts survival in older patients with multiple myeloma based on accumulation of aging-associated deficits, rather than chronological age alone, investigators report. A 16% increased risk of death was seen for each 10% increase in the deficit-accumulation frailty index (DAFI), which includes 25 variables related health, function, and activities of daily living.

There was only a weak correlation between chronological age and increase in deficits tracked by the index, in contrast to a cohort without cancer, in which age and frailty were strongly correlated, the investigators reported in JCO Clinical Cancer Informatics.

“Our results demonstrate that, for patients with multiple myeloma, chronological age alone is not a good measure for assessing overall health,” study author Tanya M. Wildes, MD, of Washington University, St. Louis, said in a news release from the American Society of Clinical Oncology.

Existing tools to assess frailty include an index proposed by the International Myeloma Working Group that looks at age plus other indexes related to comorbidities and activities of daily living, and the revised Myeloma Comorbidity Index that incorporates age with other prognostic factors.

“Although both tools provide prognostic information, chronological age automatically increases frailty without taking biologic or functional age into account,” Dr. Wildes and her coauthors wrote in their report.

By contrast, the DAFI is based on the concept of biologic age, in which the health status of an individual is measured based on the proportion of aging-associated deficits they have accumulated, according to the authors.

To create the DAFI, Dr. Wildes and her colleagues analyzed nearly 2.7 million records of noncancer patients aged 66 years or older in the SEER Medicare Health Outcomes Survey (MHOS) database. They identified 25 variables in the database representing chronic health conditions, activities of daily living, functioning, mental health, and general health.

An individual’s DAFI score was calculated as the sum of scores for each of the 25 variables as 0 for absent, 0.5 for limited, and 1 for present. Predicted DAFI means were calculated for each year of age and used to create age-specific cut points to determine whether an individual would be considered frail or not versus others of the same age.

“In other words, the same frailty score may qualify an 80-year-old individual as fit and a 70-year-old as frail, depending on the cutoff for their respective age group,” investigators explained in their report.

They applied the index to 305 patients with newly diagnosed myeloma in the SEER-MHOS database who were 66 years of age or older (median age, 76 years) and had completed the survey within 1 year of diagnosis.

The DAFI classified 52% of the myeloma patients as frail, and for that group, median overall survival was 26.8 months, versus 43.7 months for nonfrail patients (P = .015), according to the reported data. For each 10% increase in score, the risk of death increased by 16% (P less than .001).

Notably, advancing age was very weakly correlated with increased age-related deficits in the myeloma cohort (r2 = 0.15; P = .010), according to investigators, but very strongly correlated with deficits in the cohort of noncancer patients (r2 = 0.98; P less than .001).

“This suggests that, in patients with multiple myeloma, the prevalence of impairments across domains of function, chronic comorbidities, general health, and mental health are more related to the overall burden of myeloma rather than chronological age alone,” the investigators wrote.

The information used to calculate a DAFI score is easily obtainable during a clinic visit, according to the authors, who provided an overview of all 25 variables in the journal article.

Further development of a computerized program would further enhance usability in the clinic, allowing for real-time calculation during a patient visit, they said.

Survivorship expert Merry Jennifer Markham, MD, said in the ASCO news release that this frailty index is notable because it accounts for more than just chronological age. “Knowing this information can help oncologists have more informed discussions with patients about their prognosis, which in turn can empower patients and families as they weigh treatment options,” she said.

The research was supported by National Cancer Institute. Dr. Wildes reported honoraria from Carevive Systems and research funding from Janssen Oncology. Another coauthor reported honoraria from Celgene and Janssen, and a consulting or advisory role with Amgen and Takeda.

 

SOURCE: Mian HS et al. JCO Clin Cancer Inform. 2018 Jul 25. 2018 Jul 25. doi: 10.1200/CCI.18.00043.

Low serum bicarbonate and lower platelet count were among the factors that predicted a longer hospital length of stay among pediatric patients with high risk or very high risk acute lymphoblastic leukemia (ALL) who were treated with four-drug induction therapy.

©pixelcarpenter/Fotolia.com

Kasper Warrick, MD, and his colleagues at Indiana University in Indianapolis reported findings from a retrospective study of 73 ALL patients at their hospital. They performed chart reviews comparing a cohort of 42 patients who were discharged on day 4 of their induction treatment with 31 similar patients who had a longer hospital stay or admission to the intensive care unit. The report was published in Leukemia Research.

Univariate analysis found that patients with a longer length of stay were more likely to have a fever, pretransfusion hemoglobin of less than 8 g/dL, lower serum bicarbonate values, abnormal serum calcium, and abnormal serum phosphate. Multivariate stepwise logistic regression found that low serum bicarbonate and a lower platelet count on day 4 of admission was predictive of a prolonged hospital stay. About a third of patients from each group had an unplanned readmission within 30 days.

The researchers concluded that early discharge is safe in only a subgroup of high-risk ALL patients undergoing induction chemotherapy. “Treating physicians could opt for a discharge only after normalization of electrolyte abnormalities and renal functions, and when no transfusion support is needed (stable hematocrit and platelet count),” they wrote. Even in those cases, they recommended “aggressive and close outpatient follow” since patients are vulnerable to complications and readmissions.

[email protected]

SOURCE: Warrick K et al. Leuk Res. 2018 Jun 30:71:36-42.
 

Low serum bicarbonate and lower platelet count were among the factors that predicted a longer hospital length of stay among pediatric patients with high risk or very high risk acute lymphoblastic leukemia (ALL) who were treated with four-drug induction therapy.

©pixelcarpenter/Fotolia.com

Kasper Warrick, MD, and his colleagues at Indiana University in Indianapolis reported findings from a retrospective study of 73 ALL patients at their hospital. They performed chart reviews comparing a cohort of 42 patients who were discharged on day 4 of their induction treatment with 31 similar patients who had a longer hospital stay or admission to the intensive care unit. The report was published in Leukemia Research.

Univariate analysis found that patients with a longer length of stay were more likely to have a fever, pretransfusion hemoglobin of less than 8 g/dL, lower serum bicarbonate values, abnormal serum calcium, and abnormal serum phosphate. Multivariate stepwise logistic regression found that low serum bicarbonate and a lower platelet count on day 4 of admission was predictive of a prolonged hospital stay. About a third of patients from each group had an unplanned readmission within 30 days.

The researchers concluded that early discharge is safe in only a subgroup of high-risk ALL patients undergoing induction chemotherapy. “Treating physicians could opt for a discharge only after normalization of electrolyte abnormalities and renal functions, and when no transfusion support is needed (stable hematocrit and platelet count),” they wrote. Even in those cases, they recommended “aggressive and close outpatient follow” since patients are vulnerable to complications and readmissions.

[email protected]

SOURCE: Warrick K et al. Leuk Res. 2018 Jun 30:71:36-42.
 

Low serum bicarbonate and lower platelet count were among the factors that predicted a longer hospital length of stay among pediatric patients with high risk or very high risk acute lymphoblastic leukemia (ALL) who were treated with four-drug induction therapy.

©pixelcarpenter/Fotolia.com

Kasper Warrick, MD, and his colleagues at Indiana University in Indianapolis reported findings from a retrospective study of 73 ALL patients at their hospital. They performed chart reviews comparing a cohort of 42 patients who were discharged on day 4 of their induction treatment with 31 similar patients who had a longer hospital stay or admission to the intensive care unit. The report was published in Leukemia Research.

Univariate analysis found that patients with a longer length of stay were more likely to have a fever, pretransfusion hemoglobin of less than 8 g/dL, lower serum bicarbonate values, abnormal serum calcium, and abnormal serum phosphate. Multivariate stepwise logistic regression found that low serum bicarbonate and a lower platelet count on day 4 of admission was predictive of a prolonged hospital stay. About a third of patients from each group had an unplanned readmission within 30 days.

The researchers concluded that early discharge is safe in only a subgroup of high-risk ALL patients undergoing induction chemotherapy. “Treating physicians could opt for a discharge only after normalization of electrolyte abnormalities and renal functions, and when no transfusion support is needed (stable hematocrit and platelet count),” they wrote. Even in those cases, they recommended “aggressive and close outpatient follow” since patients are vulnerable to complications and readmissions.

[email protected]

SOURCE: Warrick K et al. Leuk Res. 2018 Jun 30:71:36-42.
 

Ixazomib significantly improved progression-free survival as a maintenance therapy in adults with multiple myeloma who had responded to high-dose therapy and autologous stem cell transplant.

The drug’s sponsor, Takeda, announced that the oral proteasome inhibitor had met the primary endpoint – progression-free survival versus placebo – in the randomized, phase 3 TOURMALINE-MM3 study. They also reported that adverse events were consistent with previously reported results for single-agent use of ixazomib and that there were no new safety signals.

Full study results will be presented at the annual meeting of the American Society of Hematology. Company officials plan to submit the trial data to the Food and Drug Administration and regulatory agencies around the world to gain approval of ixazomib as a single-agent maintenance therapy, according to a Takeda announcement.

The TOURMALINE-MM3 study is a double-blind study of 656 patients with multiple myeloma who have had complete response, very good partial response, or partial response to induction therapy followed by high-dose therapy and autologous stem cell transplant. In addition to progression-free survival, the trial assessed overall survival.

[email protected]

Ixazomib significantly improved progression-free survival as a maintenance therapy in adults with multiple myeloma who had responded to high-dose therapy and autologous stem cell transplant.

The drug’s sponsor, Takeda, announced that the oral proteasome inhibitor had met the primary endpoint – progression-free survival versus placebo – in the randomized, phase 3 TOURMALINE-MM3 study. They also reported that adverse events were consistent with previously reported results for single-agent use of ixazomib and that there were no new safety signals.

Full study results will be presented at the annual meeting of the American Society of Hematology. Company officials plan to submit the trial data to the Food and Drug Administration and regulatory agencies around the world to gain approval of ixazomib as a single-agent maintenance therapy, according to a Takeda announcement.

The TOURMALINE-MM3 study is a double-blind study of 656 patients with multiple myeloma who have had complete response, very good partial response, or partial response to induction therapy followed by high-dose therapy and autologous stem cell transplant. In addition to progression-free survival, the trial assessed overall survival.

[email protected]

Ixazomib significantly improved progression-free survival as a maintenance therapy in adults with multiple myeloma who had responded to high-dose therapy and autologous stem cell transplant.

The drug’s sponsor, Takeda, announced that the oral proteasome inhibitor had met the primary endpoint – progression-free survival versus placebo – in the randomized, phase 3 TOURMALINE-MM3 study. They also reported that adverse events were consistent with previously reported results for single-agent use of ixazomib and that there were no new safety signals.

Full study results will be presented at the annual meeting of the American Society of Hematology. Company officials plan to submit the trial data to the Food and Drug Administration and regulatory agencies around the world to gain approval of ixazomib as a single-agent maintenance therapy, according to a Takeda announcement.

The TOURMALINE-MM3 study is a double-blind study of 656 patients with multiple myeloma who have had complete response, very good partial response, or partial response to induction therapy followed by high-dose therapy and autologous stem cell transplant. In addition to progression-free survival, the trial assessed overall survival.

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Individuals who develop acute myeloid leukemia (AML) may have somatic mutations detectable years before diagnosis, a newly published analysis shows.

Mutations in IDH1, IDH2, TP53, DNMT3A, TET2, and spliceosome genes at baseline assessment increased the odds of developing AML with a median follow-up of 9.6 years in the study, which was based on blood samples from participants in the Women’s Health Initiative (WHI).

The findings suggest a “premalignant landscape of mutations” that may precede overt AML by many years, according to Pinkal Desai, MD, assistant professor of medicine at Cornell University and oncologist at New York–Presbyterian/Weill Cornell Medical Center, New York, and her coauthors.

“The ability to detect and identify high-risk mutations suggests that monitoring strategies for patients, as well as clinical trials of potentially preventative or disease-intercepting interventions should be considered,” wrote Dr. Desai and her colleagues. The report was published in Nature Medicine.

Their analysis comprised 212 women who participated in the WHI who were healthy at the baseline evaluation but went on to develop AML during follow-up. They performed deep sequencing on peripheral blood DNA for these cases and for 212 age-matched controls.

Women who developed AML were more likely than were controls to have mutations in baseline assessment (odds ratio, 4.86; 95% confidence interval, 3.07-7.77), and had demonstrated greater clonal complexity versus controls (comutations in 46.8% and 5.5%, respectively; odds ratio, 9.01; 95% CI, 4.1-21.4), investigators found.

©GunarsB/Thinkstock

All 21 patients with TP53 mutations went on to develop AML, as did all 15 with IDH1 or IDH2 mutations and all 3 with RUNX1 mutations. Multivariate analysis showed that TP53, IDH1 and IDH2, TET2, DNMT3A and several spliceosome genes were associated with significantly increased odds of AML versus controls.

Based on these results, Dr. Desai and colleagues proposed that patients at increased AML risk should be followed in long-term monitoring studies that incorporate next-generation sequencing.

“Data from these studies will provide a robust rationale for clinical trials of preventative intervention strategies in populations at high risk of developing AML,” they wrote.

In clinical practice, monitoring individuals for AML-associated mutations will become more feasible as costs decrease and new therapies with favorable toxicity profiles are introduced, they added.

“Molecularly targeted therapy is already available for IDH2 mutations and is under development for mutations in other candidate genes found in this study including IDH1, TP53 and spliceosome genes,” they wrote.

The authors reported having no relevant financial disclosures. The WHI program is funded by the National Institutes of Health.

SOURCE: Desai P et al. Nat Med. 2018;24:1015-23.

Individuals who develop acute myeloid leukemia (AML) may have somatic mutations detectable years before diagnosis, a newly published analysis shows.

Mutations in IDH1, IDH2, TP53, DNMT3A, TET2, and spliceosome genes at baseline assessment increased the odds of developing AML with a median follow-up of 9.6 years in the study, which was based on blood samples from participants in the Women’s Health Initiative (WHI).

The findings suggest a “premalignant landscape of mutations” that may precede overt AML by many years, according to Pinkal Desai, MD, assistant professor of medicine at Cornell University and oncologist at New York–Presbyterian/Weill Cornell Medical Center, New York, and her coauthors.

“The ability to detect and identify high-risk mutations suggests that monitoring strategies for patients, as well as clinical trials of potentially preventative or disease-intercepting interventions should be considered,” wrote Dr. Desai and her colleagues. The report was published in Nature Medicine.

Their analysis comprised 212 women who participated in the WHI who were healthy at the baseline evaluation but went on to develop AML during follow-up. They performed deep sequencing on peripheral blood DNA for these cases and for 212 age-matched controls.

Women who developed AML were more likely than were controls to have mutations in baseline assessment (odds ratio, 4.86; 95% confidence interval, 3.07-7.77), and had demonstrated greater clonal complexity versus controls (comutations in 46.8% and 5.5%, respectively; odds ratio, 9.01; 95% CI, 4.1-21.4), investigators found.

©GunarsB/Thinkstock

All 21 patients with TP53 mutations went on to develop AML, as did all 15 with IDH1 or IDH2 mutations and all 3 with RUNX1 mutations. Multivariate analysis showed that TP53, IDH1 and IDH2, TET2, DNMT3A and several spliceosome genes were associated with significantly increased odds of AML versus controls.

Based on these results, Dr. Desai and colleagues proposed that patients at increased AML risk should be followed in long-term monitoring studies that incorporate next-generation sequencing.

“Data from these studies will provide a robust rationale for clinical trials of preventative intervention strategies in populations at high risk of developing AML,” they wrote.

In clinical practice, monitoring individuals for AML-associated mutations will become more feasible as costs decrease and new therapies with favorable toxicity profiles are introduced, they added.

“Molecularly targeted therapy is already available for IDH2 mutations and is under development for mutations in other candidate genes found in this study including IDH1, TP53 and spliceosome genes,” they wrote.

The authors reported having no relevant financial disclosures. The WHI program is funded by the National Institutes of Health.

SOURCE: Desai P et al. Nat Med. 2018;24:1015-23.

Individuals who develop acute myeloid leukemia (AML) may have somatic mutations detectable years before diagnosis, a newly published analysis shows.

Mutations in IDH1, IDH2, TP53, DNMT3A, TET2, and spliceosome genes at baseline assessment increased the odds of developing AML with a median follow-up of 9.6 years in the study, which was based on blood samples from participants in the Women’s Health Initiative (WHI).

The findings suggest a “premalignant landscape of mutations” that may precede overt AML by many years, according to Pinkal Desai, MD, assistant professor of medicine at Cornell University and oncologist at New York–Presbyterian/Weill Cornell Medical Center, New York, and her coauthors.

“The ability to detect and identify high-risk mutations suggests that monitoring strategies for patients, as well as clinical trials of potentially preventative or disease-intercepting interventions should be considered,” wrote Dr. Desai and her colleagues. The report was published in Nature Medicine.

Their analysis comprised 212 women who participated in the WHI who were healthy at the baseline evaluation but went on to develop AML during follow-up. They performed deep sequencing on peripheral blood DNA for these cases and for 212 age-matched controls.

Women who developed AML were more likely than were controls to have mutations in baseline assessment (odds ratio, 4.86; 95% confidence interval, 3.07-7.77), and had demonstrated greater clonal complexity versus controls (comutations in 46.8% and 5.5%, respectively; odds ratio, 9.01; 95% CI, 4.1-21.4), investigators found.

©GunarsB/Thinkstock

All 21 patients with TP53 mutations went on to develop AML, as did all 15 with IDH1 or IDH2 mutations and all 3 with RUNX1 mutations. Multivariate analysis showed that TP53, IDH1 and IDH2, TET2, DNMT3A and several spliceosome genes were associated with significantly increased odds of AML versus controls.

Based on these results, Dr. Desai and colleagues proposed that patients at increased AML risk should be followed in long-term monitoring studies that incorporate next-generation sequencing.

“Data from these studies will provide a robust rationale for clinical trials of preventative intervention strategies in populations at high risk of developing AML,” they wrote.

In clinical practice, monitoring individuals for AML-associated mutations will become more feasible as costs decrease and new therapies with favorable toxicity profiles are introduced, they added.

“Molecularly targeted therapy is already available for IDH2 mutations and is under development for mutations in other candidate genes found in this study including IDH1, TP53 and spliceosome genes,” they wrote.

The authors reported having no relevant financial disclosures. The WHI program is funded by the National Institutes of Health.

SOURCE: Desai P et al. Nat Med. 2018;24:1015-23.

A 70-year-old man underwent salvage therapy for multiple myeloma (MM). While on maintenance immunotherapy he developed a sternal plasmacytoma. After the fifth cycle of treatment, he developed swelling, erythema, and pain in his right testis.

The main differential diagnoses for those symptoms are infections and tumors; infection is more common, so his clinicians at Indiana University School of Medicine presumed orchitis and started him on IV antibiotics. The pain resolved, but the swelling persisted after the antibiotic course. The clinicians turned to biochemical marker screening for germ cell tumors, but those were negative. Serial ultrasound imaging, which they had begun during his admission, remained unchanged.

Meanwhile, the patient’s chemotherapy was being held back, and he developed another sternal mass, prompting a fluorodeoxyglucose-positron emission tomography–computed tomography (PET/CT) scan to evaluate for relapse of myeloma. The scan revealed an enlarged, diffusely hypermetabolic right testicle. Believing the symptoms were related to the myeloma and not orchitis, the clinicians advised a radical orchiectomy.

A biopsy after the surgery showed tumor cells consistent with testicular plasmacytoma.

While rare, testicular plasmacytoma is commonly associated with MM, especially in the later stages, when cancer cells are more aggressive and not relying on bone marrow for survival, the clinicians say. Unlike myeloma, which typically spreads via blood to bone sites, testicular plasmacytoma may spread via lymphatic channels to the regional lymph nodes and subsequently to distant sites, the clinicians add, similarly to lymphoma or germ cell tumor.

It is hard to diagnose, though. The clinicians say the patient’s case illustrates the challenges. Imaging studies such as ultrasound and CT scans are not specific. And although FDG-PET/CT imaging is a standard staging tool for myeloma and helpful in identifying plasmacytoma when evidenced as intramedullary or extramedullary hypermetabolic lesions, hypermetabolic lesions are not always malignant, they note. FDG-PET/CT can’t differentiate between orchitis and testicular plasmacytoma.  Biopsy remains the diagnostic gold standard.

Source:
Schiavo C, Mann SA, Mer J, Suvannasankha A. BMJ Case Rep. 2018;pii:bcr-2017-222046.
doi: 10.1136/bcr-2017-222046.

A 70-year-old man underwent salvage therapy for multiple myeloma (MM). While on maintenance immunotherapy he developed a sternal plasmacytoma. After the fifth cycle of treatment, he developed swelling, erythema, and pain in his right testis.

The main differential diagnoses for those symptoms are infections and tumors; infection is more common, so his clinicians at Indiana University School of Medicine presumed orchitis and started him on IV antibiotics. The pain resolved, but the swelling persisted after the antibiotic course. The clinicians turned to biochemical marker screening for germ cell tumors, but those were negative. Serial ultrasound imaging, which they had begun during his admission, remained unchanged.

Meanwhile, the patient’s chemotherapy was being held back, and he developed another sternal mass, prompting a fluorodeoxyglucose-positron emission tomography–computed tomography (PET/CT) scan to evaluate for relapse of myeloma. The scan revealed an enlarged, diffusely hypermetabolic right testicle. Believing the symptoms were related to the myeloma and not orchitis, the clinicians advised a radical orchiectomy.

A biopsy after the surgery showed tumor cells consistent with testicular plasmacytoma.

While rare, testicular plasmacytoma is commonly associated with MM, especially in the later stages, when cancer cells are more aggressive and not relying on bone marrow for survival, the clinicians say. Unlike myeloma, which typically spreads via blood to bone sites, testicular plasmacytoma may spread via lymphatic channels to the regional lymph nodes and subsequently to distant sites, the clinicians add, similarly to lymphoma or germ cell tumor.

It is hard to diagnose, though. The clinicians say the patient’s case illustrates the challenges. Imaging studies such as ultrasound and CT scans are not specific. And although FDG-PET/CT imaging is a standard staging tool for myeloma and helpful in identifying plasmacytoma when evidenced as intramedullary or extramedullary hypermetabolic lesions, hypermetabolic lesions are not always malignant, they note. FDG-PET/CT can’t differentiate between orchitis and testicular plasmacytoma.  Biopsy remains the diagnostic gold standard.

Source:
Schiavo C, Mann SA, Mer J, Suvannasankha A. BMJ Case Rep. 2018;pii:bcr-2017-222046.
doi: 10.1136/bcr-2017-222046.

A 70-year-old man underwent salvage therapy for multiple myeloma (MM). While on maintenance immunotherapy he developed a sternal plasmacytoma. After the fifth cycle of treatment, he developed swelling, erythema, and pain in his right testis.

The main differential diagnoses for those symptoms are infections and tumors; infection is more common, so his clinicians at Indiana University School of Medicine presumed orchitis and started him on IV antibiotics. The pain resolved, but the swelling persisted after the antibiotic course. The clinicians turned to biochemical marker screening for germ cell tumors, but those were negative. Serial ultrasound imaging, which they had begun during his admission, remained unchanged.

Meanwhile, the patient’s chemotherapy was being held back, and he developed another sternal mass, prompting a fluorodeoxyglucose-positron emission tomography–computed tomography (PET/CT) scan to evaluate for relapse of myeloma. The scan revealed an enlarged, diffusely hypermetabolic right testicle. Believing the symptoms were related to the myeloma and not orchitis, the clinicians advised a radical orchiectomy.

A biopsy after the surgery showed tumor cells consistent with testicular plasmacytoma.

While rare, testicular plasmacytoma is commonly associated with MM, especially in the later stages, when cancer cells are more aggressive and not relying on bone marrow for survival, the clinicians say. Unlike myeloma, which typically spreads via blood to bone sites, testicular plasmacytoma may spread via lymphatic channels to the regional lymph nodes and subsequently to distant sites, the clinicians add, similarly to lymphoma or germ cell tumor.

It is hard to diagnose, though. The clinicians say the patient’s case illustrates the challenges. Imaging studies such as ultrasound and CT scans are not specific. And although FDG-PET/CT imaging is a standard staging tool for myeloma and helpful in identifying plasmacytoma when evidenced as intramedullary or extramedullary hypermetabolic lesions, hypermetabolic lesions are not always malignant, they note. FDG-PET/CT can’t differentiate between orchitis and testicular plasmacytoma.  Biopsy remains the diagnostic gold standard.

Source:
Schiavo C, Mann SA, Mer J, Suvannasankha A. BMJ Case Rep. 2018;pii:bcr-2017-222046.
doi: 10.1136/bcr-2017-222046.