Anemia

Micrograph showing MDS

Genetic profiling can be used to determine which patients with myelodysplastic syndrome (MDS) are likely to benefit from allogeneic hematopoietic stem cell transplant (HSCT), according to research published in NEJM.

Targeted sequencing of 129 genes revealed mutations that, after adjustment for clinical variables, were associated with shorter survival and/or relapse after HSCT.

Patients with mutations in TP53, JAK2, and the RAS pathway tended to have worse outcomes after HSCT than patients without such mutations.

“Although donor stem cell transplantation is the only curative therapy for MDS, many patients die after transplantation, largely due to relapse of the disease or complications relating to the transplant itself,” said study author R. Coleman Lindsley, MD, PhD, of Dana-Farber Cancer Institute in Boston, Massachusetts.

“As physicians, one of our major challenges is to be able to predict which patients are most likely to benefit from a transplant. Improving our ability to identify patients who are most likely to have a relapse or to experience life-threatening complications from a transplant could lead to better pre-transplant therapies and strategies for preventing relapse.”

Researchers have long known that specific genetic mutations are closely related to the course MDS takes. With this study, Dr Lindsley and his colleagues sought to discover whether mutations can be used to predict how patients will fare following allogeneic HSCT.

The team analyzed blood samples from 1514 MDS patients, performing targeted sequencing of 129 genes. The genes were selected based on their known or suspected involvement in the pathogenesis of myeloid cancers or bone marrow failure syndromes.

Dr Lindsley and his colleagues then evaluated the association between mutations and HSCT outcomes, including overall survival, relapse, and death without relapse.

After adjusting for significant clinical variables, the researchers found that having mutated TP53 was significantly associated with shorter survival and shorter time to relapse after HSCT (P<0.001 for both comparisons). This was true whether patients received standard conditioning or reduced-intensity conditioning.

In patients age 40 and older who did not have TP53 mutations, mutations in RAS pathway genes (P=0.004) or JAK2 (P=0.001) were significantly associated with shorter survival.

The shorter survival in patients with mutated RAS pathway genes was due to a higher risk of relapse, while the shorter survival in patients with JAK2 mutations was due to a higher risk of death without relapse.

In contrast to TP53 mutations, the adverse effect of RAS mutations on survival and risk of relapse was evident only in patients who received reduced-intensity conditioning (P<0.001). This suggests these patients may benefit from higher intensity conditioning regimens, the researchers said.

This study also yielded insights about the biology of MDS in specific groups of patients.

For example, the researchers found that 4% of MDS patients between the ages of 18 and 40 had mutations associated with Shwachman-Diamond syndrome (in the SBDS gene), but most of them had not previously been diagnosed with the syndrome.

In each case, the patients had acquired a TP53 mutation, suggesting not only how MDS develops in patients with Schwachman-Diamond syndrome but also what underlies their poor prognosis after HSCT.

The researchers also analyzed patients with therapy-related MDS. The team found that TP53 mutations and mutations in PPM1D, a gene that regulates TP53 function, were far more common in these patients than in those with primary MDS (15% and 3%, respectively, P<0.001).

“In deciding whether a stem cell transplant is appropriate for a patient with MDS, it’s always necessary to balance the potential benefit with the risk of complications,” Dr Lindsley noted.

“Our findings offer physicians a guide—based on the genetic profile of the disease and certain clinical factors—to identifying patients for whom a transplant is appropriate, and the intensity of treatment most likely to be effective.”

Micrograph showing MDS

Genetic profiling can be used to determine which patients with myelodysplastic syndrome (MDS) are likely to benefit from allogeneic hematopoietic stem cell transplant (HSCT), according to research published in NEJM.

Targeted sequencing of 129 genes revealed mutations that, after adjustment for clinical variables, were associated with shorter survival and/or relapse after HSCT.

Patients with mutations in TP53, JAK2, and the RAS pathway tended to have worse outcomes after HSCT than patients without such mutations.

“Although donor stem cell transplantation is the only curative therapy for MDS, many patients die after transplantation, largely due to relapse of the disease or complications relating to the transplant itself,” said study author R. Coleman Lindsley, MD, PhD, of Dana-Farber Cancer Institute in Boston, Massachusetts.

“As physicians, one of our major challenges is to be able to predict which patients are most likely to benefit from a transplant. Improving our ability to identify patients who are most likely to have a relapse or to experience life-threatening complications from a transplant could lead to better pre-transplant therapies and strategies for preventing relapse.”

Researchers have long known that specific genetic mutations are closely related to the course MDS takes. With this study, Dr Lindsley and his colleagues sought to discover whether mutations can be used to predict how patients will fare following allogeneic HSCT.

The team analyzed blood samples from 1514 MDS patients, performing targeted sequencing of 129 genes. The genes were selected based on their known or suspected involvement in the pathogenesis of myeloid cancers or bone marrow failure syndromes.

Dr Lindsley and his colleagues then evaluated the association between mutations and HSCT outcomes, including overall survival, relapse, and death without relapse.

After adjusting for significant clinical variables, the researchers found that having mutated TP53 was significantly associated with shorter survival and shorter time to relapse after HSCT (P<0.001 for both comparisons). This was true whether patients received standard conditioning or reduced-intensity conditioning.

In patients age 40 and older who did not have TP53 mutations, mutations in RAS pathway genes (P=0.004) or JAK2 (P=0.001) were significantly associated with shorter survival.

The shorter survival in patients with mutated RAS pathway genes was due to a higher risk of relapse, while the shorter survival in patients with JAK2 mutations was due to a higher risk of death without relapse.

In contrast to TP53 mutations, the adverse effect of RAS mutations on survival and risk of relapse was evident only in patients who received reduced-intensity conditioning (P<0.001). This suggests these patients may benefit from higher intensity conditioning regimens, the researchers said.

This study also yielded insights about the biology of MDS in specific groups of patients.

For example, the researchers found that 4% of MDS patients between the ages of 18 and 40 had mutations associated with Shwachman-Diamond syndrome (in the SBDS gene), but most of them had not previously been diagnosed with the syndrome.

In each case, the patients had acquired a TP53 mutation, suggesting not only how MDS develops in patients with Schwachman-Diamond syndrome but also what underlies their poor prognosis after HSCT.

The researchers also analyzed patients with therapy-related MDS. The team found that TP53 mutations and mutations in PPM1D, a gene that regulates TP53 function, were far more common in these patients than in those with primary MDS (15% and 3%, respectively, P<0.001).

“In deciding whether a stem cell transplant is appropriate for a patient with MDS, it’s always necessary to balance the potential benefit with the risk of complications,” Dr Lindsley noted.

“Our findings offer physicians a guide—based on the genetic profile of the disease and certain clinical factors—to identifying patients for whom a transplant is appropriate, and the intensity of treatment most likely to be effective.”

Micrograph showing MDS

Genetic profiling can be used to determine which patients with myelodysplastic syndrome (MDS) are likely to benefit from allogeneic hematopoietic stem cell transplant (HSCT), according to research published in NEJM.

Targeted sequencing of 129 genes revealed mutations that, after adjustment for clinical variables, were associated with shorter survival and/or relapse after HSCT.

Patients with mutations in TP53, JAK2, and the RAS pathway tended to have worse outcomes after HSCT than patients without such mutations.

“Although donor stem cell transplantation is the only curative therapy for MDS, many patients die after transplantation, largely due to relapse of the disease or complications relating to the transplant itself,” said study author R. Coleman Lindsley, MD, PhD, of Dana-Farber Cancer Institute in Boston, Massachusetts.

“As physicians, one of our major challenges is to be able to predict which patients are most likely to benefit from a transplant. Improving our ability to identify patients who are most likely to have a relapse or to experience life-threatening complications from a transplant could lead to better pre-transplant therapies and strategies for preventing relapse.”

Researchers have long known that specific genetic mutations are closely related to the course MDS takes. With this study, Dr Lindsley and his colleagues sought to discover whether mutations can be used to predict how patients will fare following allogeneic HSCT.

The team analyzed blood samples from 1514 MDS patients, performing targeted sequencing of 129 genes. The genes were selected based on their known or suspected involvement in the pathogenesis of myeloid cancers or bone marrow failure syndromes.

Dr Lindsley and his colleagues then evaluated the association between mutations and HSCT outcomes, including overall survival, relapse, and death without relapse.

After adjusting for significant clinical variables, the researchers found that having mutated TP53 was significantly associated with shorter survival and shorter time to relapse after HSCT (P<0.001 for both comparisons). This was true whether patients received standard conditioning or reduced-intensity conditioning.

In patients age 40 and older who did not have TP53 mutations, mutations in RAS pathway genes (P=0.004) or JAK2 (P=0.001) were significantly associated with shorter survival.

The shorter survival in patients with mutated RAS pathway genes was due to a higher risk of relapse, while the shorter survival in patients with JAK2 mutations was due to a higher risk of death without relapse.

In contrast to TP53 mutations, the adverse effect of RAS mutations on survival and risk of relapse was evident only in patients who received reduced-intensity conditioning (P<0.001). This suggests these patients may benefit from higher intensity conditioning regimens, the researchers said.

This study also yielded insights about the biology of MDS in specific groups of patients.

For example, the researchers found that 4% of MDS patients between the ages of 18 and 40 had mutations associated with Shwachman-Diamond syndrome (in the SBDS gene), but most of them had not previously been diagnosed with the syndrome.

In each case, the patients had acquired a TP53 mutation, suggesting not only how MDS develops in patients with Schwachman-Diamond syndrome but also what underlies their poor prognosis after HSCT.

The researchers also analyzed patients with therapy-related MDS. The team found that TP53 mutations and mutations in PPM1D, a gene that regulates TP53 function, were far more common in these patients than in those with primary MDS (15% and 3%, respectively, P<0.001).

“In deciding whether a stem cell transplant is appropriate for a patient with MDS, it’s always necessary to balance the potential benefit with the risk of complications,” Dr Lindsley noted.

“Our findings offer physicians a guide—based on the genetic profile of the disease and certain clinical factors—to identifying patients for whom a transplant is appropriate, and the intensity of treatment most likely to be effective.”

RBCs made by iPSCs generated
from cells from a DBA patient
Image courtesy of
Boston Children’s Hospital

Researchers have used induced pluripotent stem cells (iPSCs) to identify a compound that could treat Diamond Blackfan anemia (DBA).

The team used iPSCs to generate expandable hematopoietic progenitor cells (HPCs) that recapitulate the defects in erythroid differentiation observed in patients with DBA.

The researchers then used the HPCs to screen chemical compounds that might be used to treat DBA.

One of these compounds, SMER28, enhanced erythropoiesis in models of DBA.

“It is very satisfying as physician-scientists to find new potential treatments for rare blood diseases such as Diamond Blackfan anemia,” said study author Leonard Zon, MD, of Boston Children’s Hospital and Dana-Farber Cancer Institute in Boston, Massachusetts.

Dr Zon and his colleagues described this work in Science Translational Medicine.

The researchers first took fibroblasts from 2 patients with DBA and reprogrammed them into iPSCs. From the iPSCs, the team generated HPCs, which they loaded into a high-throughput drug screening system.

Testing a library of 1440 chemicals, the researchers found several that showed promise for treating DBA in vitro. One compound, SMER28, was able to induce red blood cell (RBC) production in mice and zebrafish.

The researchers believe this study marks an important advance in the stem cell field.

“[iPSCs] have been hard to instruct when it comes to making blood,” said study author Sergei Doulatov, PhD, of the University of Washington in Seattle.

“This is the first time [iPSCs] have been used to identify a drug to treat a blood disorder.”

Making RBCs

As in DBA itself, the patient-derived HPCs, studied in vitro, failed to generate erythroid cells. The same was true when the cells were transplanted into mice.

However, the chemical screen got several “hits.” In wells loaded with certain chemicals, erythroid cells began appearing. Because of its especially strong effect, SMER28 was put through additional testing.

When SMER28 was used to treat the marrow in zebrafish and mouse models of DBA, the animals made erythroid progenitor cells that, in turn, made RBCs, reversing or stabilizing anemia. The same was true in cells from DBA patients transplanted into mice.

The higher the dose of SMER28, the more RBCs were produced, and no ill effects were found. However, formal toxicity studies have not been conducted.

SMER28 has been tested preclinically for some neurodegenerative diseases. It activates an autophagy pathway that recycles damaged cellular components.

In DBA, SMER28 appears to turn on autophagy in erythroid progenitors. Dr Doulatov plans to further explore how this interferes with RBC production.

RBCs made by iPSCs generated
from cells from a DBA patient
Image courtesy of
Boston Children’s Hospital

Researchers have used induced pluripotent stem cells (iPSCs) to identify a compound that could treat Diamond Blackfan anemia (DBA).

The team used iPSCs to generate expandable hematopoietic progenitor cells (HPCs) that recapitulate the defects in erythroid differentiation observed in patients with DBA.

The researchers then used the HPCs to screen chemical compounds that might be used to treat DBA.

One of these compounds, SMER28, enhanced erythropoiesis in models of DBA.

“It is very satisfying as physician-scientists to find new potential treatments for rare blood diseases such as Diamond Blackfan anemia,” said study author Leonard Zon, MD, of Boston Children’s Hospital and Dana-Farber Cancer Institute in Boston, Massachusetts.

Dr Zon and his colleagues described this work in Science Translational Medicine.

The researchers first took fibroblasts from 2 patients with DBA and reprogrammed them into iPSCs. From the iPSCs, the team generated HPCs, which they loaded into a high-throughput drug screening system.

Testing a library of 1440 chemicals, the researchers found several that showed promise for treating DBA in vitro. One compound, SMER28, was able to induce red blood cell (RBC) production in mice and zebrafish.

The researchers believe this study marks an important advance in the stem cell field.

“[iPSCs] have been hard to instruct when it comes to making blood,” said study author Sergei Doulatov, PhD, of the University of Washington in Seattle.

“This is the first time [iPSCs] have been used to identify a drug to treat a blood disorder.”

Making RBCs

As in DBA itself, the patient-derived HPCs, studied in vitro, failed to generate erythroid cells. The same was true when the cells were transplanted into mice.

However, the chemical screen got several “hits.” In wells loaded with certain chemicals, erythroid cells began appearing. Because of its especially strong effect, SMER28 was put through additional testing.

When SMER28 was used to treat the marrow in zebrafish and mouse models of DBA, the animals made erythroid progenitor cells that, in turn, made RBCs, reversing or stabilizing anemia. The same was true in cells from DBA patients transplanted into mice.

The higher the dose of SMER28, the more RBCs were produced, and no ill effects were found. However, formal toxicity studies have not been conducted.

SMER28 has been tested preclinically for some neurodegenerative diseases. It activates an autophagy pathway that recycles damaged cellular components.

In DBA, SMER28 appears to turn on autophagy in erythroid progenitors. Dr Doulatov plans to further explore how this interferes with RBC production.

RBCs made by iPSCs generated
from cells from a DBA patient
Image courtesy of
Boston Children’s Hospital

Researchers have used induced pluripotent stem cells (iPSCs) to identify a compound that could treat Diamond Blackfan anemia (DBA).

The team used iPSCs to generate expandable hematopoietic progenitor cells (HPCs) that recapitulate the defects in erythroid differentiation observed in patients with DBA.

The researchers then used the HPCs to screen chemical compounds that might be used to treat DBA.

One of these compounds, SMER28, enhanced erythropoiesis in models of DBA.

“It is very satisfying as physician-scientists to find new potential treatments for rare blood diseases such as Diamond Blackfan anemia,” said study author Leonard Zon, MD, of Boston Children’s Hospital and Dana-Farber Cancer Institute in Boston, Massachusetts.

Dr Zon and his colleagues described this work in Science Translational Medicine.

The researchers first took fibroblasts from 2 patients with DBA and reprogrammed them into iPSCs. From the iPSCs, the team generated HPCs, which they loaded into a high-throughput drug screening system.

Testing a library of 1440 chemicals, the researchers found several that showed promise for treating DBA in vitro. One compound, SMER28, was able to induce red blood cell (RBC) production in mice and zebrafish.

The researchers believe this study marks an important advance in the stem cell field.

“[iPSCs] have been hard to instruct when it comes to making blood,” said study author Sergei Doulatov, PhD, of the University of Washington in Seattle.

“This is the first time [iPSCs] have been used to identify a drug to treat a blood disorder.”

Making RBCs

As in DBA itself, the patient-derived HPCs, studied in vitro, failed to generate erythroid cells. The same was true when the cells were transplanted into mice.

However, the chemical screen got several “hits.” In wells loaded with certain chemicals, erythroid cells began appearing. Because of its especially strong effect, SMER28 was put through additional testing.

When SMER28 was used to treat the marrow in zebrafish and mouse models of DBA, the animals made erythroid progenitor cells that, in turn, made RBCs, reversing or stabilizing anemia. The same was true in cells from DBA patients transplanted into mice.

The higher the dose of SMER28, the more RBCs were produced, and no ill effects were found. However, formal toxicity studies have not been conducted.

SMER28 has been tested preclinically for some neurodegenerative diseases. It activates an autophagy pathway that recycles damaged cellular components.

In DBA, SMER28 appears to turn on autophagy in erythroid progenitors. Dr Doulatov plans to further explore how this interferes with RBC production.

Vials of product
Photo by Bill Branson

The US Food and Drug Administration (FDA) has approved an intravenous immunoglobulin (IVIG) product (Gammaplex® 10%) for the treatment of primary immunodeficiency (PI) and chronic immune thrombocytopenia (ITP) in adults. 

PI includes, but is not limited to,

the humoral immune defect in common variable immunodeficiency, X-linked and congenital

agammaglobulinemia, Wiskott-Aldrich

syndrome, and severe combined immunodeficiencies.

Gammaplex 10% is manufactured by Bio Products Laboratory Limited (BPL).

Gammaplex 10% is made with the same process as BPL’s previously approved IVIG treatment, Gammaplex® 5% (immune globulin intravenous [human], 5% liquid). 

Gammaplex 10% is more concentrated than Gammaplex 5%, with an immune globulin G (IgG) concentration of 100 g/L, and is stabilized with glycine. 

The FDA’s approval of Gammaplex 10% was based on a 2-phase, crossover bioequivalence study comparing Gammaplex 10% and Gammaplex 5% in 33 adult patients with PI. This study is the first direct comparison of 10% and 5% IVIG products in the treatment of PI.

The primary endpoint of bioequivalence between the products was achieved, and trough levels of IgG were well maintained throughout the study. 

Both Gammaplex 10% and Gammaplex 5% infusion rates were increased incrementally at 15-minute intervals if tolerated by the subject. The Gammaplex 10% infusion rate was increased to the maximum in 96% of infusions. 

The mean infusion time for Gammaplex 10% was 1 hour and 51 minutes, which was 57 minutes faster than Gammaplex 5%.

There were no notable differences in the safety and tolerability of the 2 products.

The most common adverse events in patients receiving Gammaplex 10% were headache (12.5%), migraine (6.3%), and pyrexia (6.3%). There were no serious product-related adverse events. 

The safety of Gammaplex 10% has not been established in adults with chronic ITP. The safety profile for Gammaplex 5% has been studied in a phase 3 trial of adults with chronic ITP, and it is anticipated that the safety profile for both formulations are comparable for ITP patients.

The most common adverse events in adults with chronic ITP receiving Gammaplex 5% were headache, vomiting, nausea, pyrexia, arthralgia, and dehydration. Serious adverse events were headache, vomiting, and dehydration.

The full prescribing information for Gammaplex 10%, which includes trial data, is available at http://www.gammaplex.com.

Vials of product
Photo by Bill Branson

The US Food and Drug Administration (FDA) has approved an intravenous immunoglobulin (IVIG) product (Gammaplex® 10%) for the treatment of primary immunodeficiency (PI) and chronic immune thrombocytopenia (ITP) in adults. 

PI includes, but is not limited to,

the humoral immune defect in common variable immunodeficiency, X-linked and congenital

agammaglobulinemia, Wiskott-Aldrich

syndrome, and severe combined immunodeficiencies.

Gammaplex 10% is manufactured by Bio Products Laboratory Limited (BPL).

Gammaplex 10% is made with the same process as BPL’s previously approved IVIG treatment, Gammaplex® 5% (immune globulin intravenous [human], 5% liquid). 

Gammaplex 10% is more concentrated than Gammaplex 5%, with an immune globulin G (IgG) concentration of 100 g/L, and is stabilized with glycine. 

The FDA’s approval of Gammaplex 10% was based on a 2-phase, crossover bioequivalence study comparing Gammaplex 10% and Gammaplex 5% in 33 adult patients with PI. This study is the first direct comparison of 10% and 5% IVIG products in the treatment of PI.

The primary endpoint of bioequivalence between the products was achieved, and trough levels of IgG were well maintained throughout the study. 

Both Gammaplex 10% and Gammaplex 5% infusion rates were increased incrementally at 15-minute intervals if tolerated by the subject. The Gammaplex 10% infusion rate was increased to the maximum in 96% of infusions. 

The mean infusion time for Gammaplex 10% was 1 hour and 51 minutes, which was 57 minutes faster than Gammaplex 5%.

There were no notable differences in the safety and tolerability of the 2 products.

The most common adverse events in patients receiving Gammaplex 10% were headache (12.5%), migraine (6.3%), and pyrexia (6.3%). There were no serious product-related adverse events. 

The safety of Gammaplex 10% has not been established in adults with chronic ITP. The safety profile for Gammaplex 5% has been studied in a phase 3 trial of adults with chronic ITP, and it is anticipated that the safety profile for both formulations are comparable for ITP patients.

The most common adverse events in adults with chronic ITP receiving Gammaplex 5% were headache, vomiting, nausea, pyrexia, arthralgia, and dehydration. Serious adverse events were headache, vomiting, and dehydration.

The full prescribing information for Gammaplex 10%, which includes trial data, is available at http://www.gammaplex.com.

Vials of product
Photo by Bill Branson

The US Food and Drug Administration (FDA) has approved an intravenous immunoglobulin (IVIG) product (Gammaplex® 10%) for the treatment of primary immunodeficiency (PI) and chronic immune thrombocytopenia (ITP) in adults. 

PI includes, but is not limited to,

the humoral immune defect in common variable immunodeficiency, X-linked and congenital

agammaglobulinemia, Wiskott-Aldrich

syndrome, and severe combined immunodeficiencies.

Gammaplex 10% is manufactured by Bio Products Laboratory Limited (BPL).

Gammaplex 10% is made with the same process as BPL’s previously approved IVIG treatment, Gammaplex® 5% (immune globulin intravenous [human], 5% liquid). 

Gammaplex 10% is more concentrated than Gammaplex 5%, with an immune globulin G (IgG) concentration of 100 g/L, and is stabilized with glycine. 

The FDA’s approval of Gammaplex 10% was based on a 2-phase, crossover bioequivalence study comparing Gammaplex 10% and Gammaplex 5% in 33 adult patients with PI. This study is the first direct comparison of 10% and 5% IVIG products in the treatment of PI.

The primary endpoint of bioequivalence between the products was achieved, and trough levels of IgG were well maintained throughout the study. 

Both Gammaplex 10% and Gammaplex 5% infusion rates were increased incrementally at 15-minute intervals if tolerated by the subject. The Gammaplex 10% infusion rate was increased to the maximum in 96% of infusions. 

The mean infusion time for Gammaplex 10% was 1 hour and 51 minutes, which was 57 minutes faster than Gammaplex 5%.

There were no notable differences in the safety and tolerability of the 2 products.

The most common adverse events in patients receiving Gammaplex 10% were headache (12.5%), migraine (6.3%), and pyrexia (6.3%). There were no serious product-related adverse events. 

The safety of Gammaplex 10% has not been established in adults with chronic ITP. The safety profile for Gammaplex 5% has been studied in a phase 3 trial of adults with chronic ITP, and it is anticipated that the safety profile for both formulations are comparable for ITP patients.

The most common adverse events in adults with chronic ITP receiving Gammaplex 5% were headache, vomiting, nausea, pyrexia, arthralgia, and dehydration. Serious adverse events were headache, vomiting, and dehydration.

The full prescribing information for Gammaplex 10%, which includes trial data, is available at http://www.gammaplex.com.

Blood sample
Photo by Juan D. Alfonso

A new study suggests that hemoglobin A1c (HbA1c), a biomarker used to measure blood sugar over time, may not perform as accurately among African-Americans with sickle cell trait (SCT) and could be leading to a systemic underestimation of blood sugar control in that population.

Researchers analyzed data from more than 4600 people and found that HbA1c readings were significantly lower in individuals with SCT than in those without it, even after accounting for several possible confounding factors.

The team reported these findings in JAMA. 

“We found that HbA1c was systematically lower in African-Americans with sickle cell trait than those without sickle cell trait, despite similar blood sugar measurements using other tests,” said study author Mary Lacy, a doctoral candidate at the Brown University School of Public Health in Providence, Rhode Island.

“We might be missing an opportunity for diagnosis and treatment of a serious disease.”

Lacy and her co-authors found that using standard clinical HbA1c cutoffs resulted in identifying 40% fewer potential cases of prediabetes and 48% fewer potential cases of diabetes in people with SCT than in people without SCT.

However, when the researchers used other blood glucose measures as the diagnostic criteria, they found no significant difference in the likelihood of diabetes and prediabetes among patients with or without SCT.

The questions the study raises about using HbA1c among SCT carriers matter for treatment as well as diagnosis, said study author Wen-Chih Wu, MD, of Brown University.

“The clinical implications of these results are highly relevant,” Dr Wu said. “For patients with diabetes, HbA1c is often used as a marker of how well they are managing their diabetes, so having an underestimation of their blood sugars is problematic because they might have a false sense of security, thinking they are doing okay when they are not.”

Study details

For this study, the researchers analyzed data from 2 major public health studies—the Coronary Artery Risk Development in Young Adults (CARDIA) study and the Jackson Heart Study (JHS). Of the 4620 participants included in the analysis, 367 had SCT.

Among all the patients included in the analysis, HbA1c readings came from either of 2 widely used, clinically accepted assays made by Tosoh Bioscience Inc. that rely on a process called high-performance liquid chromatography.

In addition to those measures, the researchers also compared fasting and 2-hour blood glucose and statistically controlled for demographic and medical factors, such as gender, age, body-mass index, whether diabetes had already been diagnosed, and whether it was being treated.

Study author Gregory Wellenius, ScD, of Brown University, said the study’s scale and breadth allowed for the most definitive comparison to date of HbA1c readings in patients with and without SCT. Two previous, smaller studies had not detected a similar discrepancy.

“The strengths of the study are that it’s the largest sample size ever used, it’s across 2 different studies with somewhat different populations, and it’s a more thorough evaluation than prior studies,” Dr Wellenius said.

While the study showed that HbA1c readings were significantly different between people with and without SCT, it also showed that blood glucose readings were not, suggesting that glucose metabolism is not necessarily different between the 2 groups, as the HbA1c readings alone would suggest.

Implications for practice

The study does not explain why the HbA1c readings differ. While it could be related to the assay method, which is approved by the NGSP (formerly National Glycohemoglobin Standardization Program) for use in patients with SCT, it could also be a consequence of the underlying biology of SCT.

Hypothetically, according to the researchers, if the hemoglobin variant of the trait endows red blood cells with a shorter lifespan, the cells’ hemoglobin would carry less accumulated blood glucose, leading to falsely low HbA1c readings.

“Irrespective of the reason of the underestimation, the underestimation is very real, and clinicians should consider screening for sickle cell trait and account for the difference in HbA1c,” Dr Wu said.

Yet not many people with SCT in the US know they carry the variant, especially those born before routine screenings at birth began, Lacy said.

The researchers therefore recommend that practitioners following African-American patients whose HbA1c levels are within 0.3 percentage points of a diagnostic cutoff also consider using additional blood glucose measures. Current diagnostic thresholds for A1C are ≥5.7% for prediabetes and ≥6.5% for diabetes.

Blood sample
Photo by Juan D. Alfonso

A new study suggests that hemoglobin A1c (HbA1c), a biomarker used to measure blood sugar over time, may not perform as accurately among African-Americans with sickle cell trait (SCT) and could be leading to a systemic underestimation of blood sugar control in that population.

Researchers analyzed data from more than 4600 people and found that HbA1c readings were significantly lower in individuals with SCT than in those without it, even after accounting for several possible confounding factors.

The team reported these findings in JAMA. 

“We found that HbA1c was systematically lower in African-Americans with sickle cell trait than those without sickle cell trait, despite similar blood sugar measurements using other tests,” said study author Mary Lacy, a doctoral candidate at the Brown University School of Public Health in Providence, Rhode Island.

“We might be missing an opportunity for diagnosis and treatment of a serious disease.”

Lacy and her co-authors found that using standard clinical HbA1c cutoffs resulted in identifying 40% fewer potential cases of prediabetes and 48% fewer potential cases of diabetes in people with SCT than in people without SCT.

However, when the researchers used other blood glucose measures as the diagnostic criteria, they found no significant difference in the likelihood of diabetes and prediabetes among patients with or without SCT.

The questions the study raises about using HbA1c among SCT carriers matter for treatment as well as diagnosis, said study author Wen-Chih Wu, MD, of Brown University.

“The clinical implications of these results are highly relevant,” Dr Wu said. “For patients with diabetes, HbA1c is often used as a marker of how well they are managing their diabetes, so having an underestimation of their blood sugars is problematic because they might have a false sense of security, thinking they are doing okay when they are not.”

Study details

For this study, the researchers analyzed data from 2 major public health studies—the Coronary Artery Risk Development in Young Adults (CARDIA) study and the Jackson Heart Study (JHS). Of the 4620 participants included in the analysis, 367 had SCT.

Among all the patients included in the analysis, HbA1c readings came from either of 2 widely used, clinically accepted assays made by Tosoh Bioscience Inc. that rely on a process called high-performance liquid chromatography.

In addition to those measures, the researchers also compared fasting and 2-hour blood glucose and statistically controlled for demographic and medical factors, such as gender, age, body-mass index, whether diabetes had already been diagnosed, and whether it was being treated.

Study author Gregory Wellenius, ScD, of Brown University, said the study’s scale and breadth allowed for the most definitive comparison to date of HbA1c readings in patients with and without SCT. Two previous, smaller studies had not detected a similar discrepancy.

“The strengths of the study are that it’s the largest sample size ever used, it’s across 2 different studies with somewhat different populations, and it’s a more thorough evaluation than prior studies,” Dr Wellenius said.

While the study showed that HbA1c readings were significantly different between people with and without SCT, it also showed that blood glucose readings were not, suggesting that glucose metabolism is not necessarily different between the 2 groups, as the HbA1c readings alone would suggest.

Implications for practice

The study does not explain why the HbA1c readings differ. While it could be related to the assay method, which is approved by the NGSP (formerly National Glycohemoglobin Standardization Program) for use in patients with SCT, it could also be a consequence of the underlying biology of SCT.

Hypothetically, according to the researchers, if the hemoglobin variant of the trait endows red blood cells with a shorter lifespan, the cells’ hemoglobin would carry less accumulated blood glucose, leading to falsely low HbA1c readings.

“Irrespective of the reason of the underestimation, the underestimation is very real, and clinicians should consider screening for sickle cell trait and account for the difference in HbA1c,” Dr Wu said.

Yet not many people with SCT in the US know they carry the variant, especially those born before routine screenings at birth began, Lacy said.

The researchers therefore recommend that practitioners following African-American patients whose HbA1c levels are within 0.3 percentage points of a diagnostic cutoff also consider using additional blood glucose measures. Current diagnostic thresholds for A1C are ≥5.7% for prediabetes and ≥6.5% for diabetes.

Blood sample
Photo by Juan D. Alfonso

A new study suggests that hemoglobin A1c (HbA1c), a biomarker used to measure blood sugar over time, may not perform as accurately among African-Americans with sickle cell trait (SCT) and could be leading to a systemic underestimation of blood sugar control in that population.

Researchers analyzed data from more than 4600 people and found that HbA1c readings were significantly lower in individuals with SCT than in those without it, even after accounting for several possible confounding factors.

The team reported these findings in JAMA. 

“We found that HbA1c was systematically lower in African-Americans with sickle cell trait than those without sickle cell trait, despite similar blood sugar measurements using other tests,” said study author Mary Lacy, a doctoral candidate at the Brown University School of Public Health in Providence, Rhode Island.

“We might be missing an opportunity for diagnosis and treatment of a serious disease.”

Lacy and her co-authors found that using standard clinical HbA1c cutoffs resulted in identifying 40% fewer potential cases of prediabetes and 48% fewer potential cases of diabetes in people with SCT than in people without SCT.

However, when the researchers used other blood glucose measures as the diagnostic criteria, they found no significant difference in the likelihood of diabetes and prediabetes among patients with or without SCT.

The questions the study raises about using HbA1c among SCT carriers matter for treatment as well as diagnosis, said study author Wen-Chih Wu, MD, of Brown University.

“The clinical implications of these results are highly relevant,” Dr Wu said. “For patients with diabetes, HbA1c is often used as a marker of how well they are managing their diabetes, so having an underestimation of their blood sugars is problematic because they might have a false sense of security, thinking they are doing okay when they are not.”

Study details

For this study, the researchers analyzed data from 2 major public health studies—the Coronary Artery Risk Development in Young Adults (CARDIA) study and the Jackson Heart Study (JHS). Of the 4620 participants included in the analysis, 367 had SCT.

Among all the patients included in the analysis, HbA1c readings came from either of 2 widely used, clinically accepted assays made by Tosoh Bioscience Inc. that rely on a process called high-performance liquid chromatography.

In addition to those measures, the researchers also compared fasting and 2-hour blood glucose and statistically controlled for demographic and medical factors, such as gender, age, body-mass index, whether diabetes had already been diagnosed, and whether it was being treated.

Study author Gregory Wellenius, ScD, of Brown University, said the study’s scale and breadth allowed for the most definitive comparison to date of HbA1c readings in patients with and without SCT. Two previous, smaller studies had not detected a similar discrepancy.

“The strengths of the study are that it’s the largest sample size ever used, it’s across 2 different studies with somewhat different populations, and it’s a more thorough evaluation than prior studies,” Dr Wellenius said.

While the study showed that HbA1c readings were significantly different between people with and without SCT, it also showed that blood glucose readings were not, suggesting that glucose metabolism is not necessarily different between the 2 groups, as the HbA1c readings alone would suggest.

Implications for practice

The study does not explain why the HbA1c readings differ. While it could be related to the assay method, which is approved by the NGSP (formerly National Glycohemoglobin Standardization Program) for use in patients with SCT, it could also be a consequence of the underlying biology of SCT.

Hypothetically, according to the researchers, if the hemoglobin variant of the trait endows red blood cells with a shorter lifespan, the cells’ hemoglobin would carry less accumulated blood glucose, leading to falsely low HbA1c readings.

“Irrespective of the reason of the underestimation, the underestimation is very real, and clinicians should consider screening for sickle cell trait and account for the difference in HbA1c,” Dr Wu said.

Yet not many people with SCT in the US know they carry the variant, especially those born before routine screenings at birth began, Lacy said.

The researchers therefore recommend that practitioners following African-American patients whose HbA1c levels are within 0.3 percentage points of a diagnostic cutoff also consider using additional blood glucose measures. Current diagnostic thresholds for A1C are ≥5.7% for prediabetes and ≥6.5% for diabetes.

Bone marrow harvest
Photo by Chad McNeeley

Researchers have reported a “promising” treatment approach for

refractory, severe aplastic anemia (SAA).

The

regimen consists of nonmyeloablative conditioning, bone marrow

transplants (BMTs) from “alternative” donors, and graft-vs-host disease

(GVHD) prophylaxis.

All 16 SAA patients who received this treatment

achieved engraftment and were completely cleared of disease.

There were 2 cases of acute and chronic GVHD, but they resolved.

All patients were ultimately able to stop immunosuppressive therapy.

Robert Brodsky, MD, of Sidney Kimmel Cancer Center in Baltimore, Maryland, and his colleagues reported these findings in Biology of Blood and Marrow Transplantation.

“Our findings have the potential to greatly widen treatment options for the vast majority of severe aplastic anemia patients,” Dr Brodsky said.

He and his colleagues tested their approach in 16 SAA patients between 11 and 69 years of age. Each of the patients had failed to respond to immunosuppressive therapy and other treatments.

The patients received conditioning with antithymocyte globulin, fludarabine, low-dose cyclophosphamide, and total body irradiation.

They then received BMTs. Thirteen of the donors were haploidentical related, 2 were fully matched unrelated, and 1 was mismatched unrelated.

Three and 4 days after BMT, the patients received cyclophosphamide at 50 mg/kg/day as GVHD prophylaxis. They then received mycophenolate mofetil on days 5 through 35 and tacrolimus from day 5 through 1 year.

The median time to neutrophil recovery (over 1000 × 10³/mm³ for 3 consecutive days) was 19 days (range, 16 to 27). The median time to red cell engraftment was 25 days (range, 2 to 58). And the median time to the last platelet transfusion (to keep platelet counts over 50 × 10³/mm³) was 27.5 days (range, 22 to 108).

At a median follow-up of 21 months (range, 3 to 64), all 16 patients were still alive, disease-free, and no longer required transfusions.

Two patients did develop grade 1/2 acute skin GVHD. They also had mild chronic GVHD of the skin/mouth, which required systemic steroids.

One of these patients was able to come off all immunosuppressive therapy by 15 months, and the other was able to do so by 17 months. All of the other patients stopped immunosuppressive therapy at 1 year.

Ending all therapy related to their disease has been life-changing for these patients, said study author Amy DeZern, MD, also of the Sidney Kimmel Cancer Center.

“It’s like night and day,” she said. “They go from not knowing if they have a future to hoping for what they’d hoped for before they got sick. It’s that transformative.”

Successful BMTs using partially matched donors open up the transplant option to nearly all patients with SAA, especially minority patients, added Dr Brodsky.

“Now, a therapy that used to be available to 25% to 30% of patients with severe aplastic anemia is potentially available to more than 95%,” he said.

Bone marrow harvest
Photo by Chad McNeeley

Researchers have reported a “promising” treatment approach for

refractory, severe aplastic anemia (SAA).

The

regimen consists of nonmyeloablative conditioning, bone marrow

transplants (BMTs) from “alternative” donors, and graft-vs-host disease

(GVHD) prophylaxis.

All 16 SAA patients who received this treatment

achieved engraftment and were completely cleared of disease.

There were 2 cases of acute and chronic GVHD, but they resolved.

All patients were ultimately able to stop immunosuppressive therapy.

Robert Brodsky, MD, of Sidney Kimmel Cancer Center in Baltimore, Maryland, and his colleagues reported these findings in Biology of Blood and Marrow Transplantation.

“Our findings have the potential to greatly widen treatment options for the vast majority of severe aplastic anemia patients,” Dr Brodsky said.

He and his colleagues tested their approach in 16 SAA patients between 11 and 69 years of age. Each of the patients had failed to respond to immunosuppressive therapy and other treatments.

The patients received conditioning with antithymocyte globulin, fludarabine, low-dose cyclophosphamide, and total body irradiation.

They then received BMTs. Thirteen of the donors were haploidentical related, 2 were fully matched unrelated, and 1 was mismatched unrelated.

Three and 4 days after BMT, the patients received cyclophosphamide at 50 mg/kg/day as GVHD prophylaxis. They then received mycophenolate mofetil on days 5 through 35 and tacrolimus from day 5 through 1 year.

The median time to neutrophil recovery (over 1000 × 10³/mm³ for 3 consecutive days) was 19 days (range, 16 to 27). The median time to red cell engraftment was 25 days (range, 2 to 58). And the median time to the last platelet transfusion (to keep platelet counts over 50 × 10³/mm³) was 27.5 days (range, 22 to 108).

At a median follow-up of 21 months (range, 3 to 64), all 16 patients were still alive, disease-free, and no longer required transfusions.

Two patients did develop grade 1/2 acute skin GVHD. They also had mild chronic GVHD of the skin/mouth, which required systemic steroids.

One of these patients was able to come off all immunosuppressive therapy by 15 months, and the other was able to do so by 17 months. All of the other patients stopped immunosuppressive therapy at 1 year.

Ending all therapy related to their disease has been life-changing for these patients, said study author Amy DeZern, MD, also of the Sidney Kimmel Cancer Center.

“It’s like night and day,” she said. “They go from not knowing if they have a future to hoping for what they’d hoped for before they got sick. It’s that transformative.”

Successful BMTs using partially matched donors open up the transplant option to nearly all patients with SAA, especially minority patients, added Dr Brodsky.

“Now, a therapy that used to be available to 25% to 30% of patients with severe aplastic anemia is potentially available to more than 95%,” he said.

Bone marrow harvest
Photo by Chad McNeeley

Researchers have reported a “promising” treatment approach for

refractory, severe aplastic anemia (SAA).

The

regimen consists of nonmyeloablative conditioning, bone marrow

transplants (BMTs) from “alternative” donors, and graft-vs-host disease

(GVHD) prophylaxis.

All 16 SAA patients who received this treatment

achieved engraftment and were completely cleared of disease.

There were 2 cases of acute and chronic GVHD, but they resolved.

All patients were ultimately able to stop immunosuppressive therapy.

Robert Brodsky, MD, of Sidney Kimmel Cancer Center in Baltimore, Maryland, and his colleagues reported these findings in Biology of Blood and Marrow Transplantation.

“Our findings have the potential to greatly widen treatment options for the vast majority of severe aplastic anemia patients,” Dr Brodsky said.

He and his colleagues tested their approach in 16 SAA patients between 11 and 69 years of age. Each of the patients had failed to respond to immunosuppressive therapy and other treatments.

The patients received conditioning with antithymocyte globulin, fludarabine, low-dose cyclophosphamide, and total body irradiation.

They then received BMTs. Thirteen of the donors were haploidentical related, 2 were fully matched unrelated, and 1 was mismatched unrelated.

Three and 4 days after BMT, the patients received cyclophosphamide at 50 mg/kg/day as GVHD prophylaxis. They then received mycophenolate mofetil on days 5 through 35 and tacrolimus from day 5 through 1 year.

The median time to neutrophil recovery (over 1000 × 10³/mm³ for 3 consecutive days) was 19 days (range, 16 to 27). The median time to red cell engraftment was 25 days (range, 2 to 58). And the median time to the last platelet transfusion (to keep platelet counts over 50 × 10³/mm³) was 27.5 days (range, 22 to 108).

At a median follow-up of 21 months (range, 3 to 64), all 16 patients were still alive, disease-free, and no longer required transfusions.

Two patients did develop grade 1/2 acute skin GVHD. They also had mild chronic GVHD of the skin/mouth, which required systemic steroids.

One of these patients was able to come off all immunosuppressive therapy by 15 months, and the other was able to do so by 17 months. All of the other patients stopped immunosuppressive therapy at 1 year.

Ending all therapy related to their disease has been life-changing for these patients, said study author Amy DeZern, MD, also of the Sidney Kimmel Cancer Center.

“It’s like night and day,” she said. “They go from not knowing if they have a future to hoping for what they’d hoped for before they got sick. It’s that transformative.”

Successful BMTs using partially matched donors open up the transplant option to nearly all patients with SAA, especially minority patients, added Dr Brodsky.

“Now, a therapy that used to be available to 25% to 30% of patients with severe aplastic anemia is potentially available to more than 95%,” he said.

Azathioprine tablets

Results of a large, retrospective study suggest that taking azathioprine, a drug commonly used to treat autoimmune disease, may increase a person’s risk of developing myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML).

Researchers analyzed data on more than 40,000 patients with 27 common autoimmune diseases and found that azathioprine use was significantly associated with an increased risk of MDS and AML.

“Similar associations were already documented in case reports and case series but have never been evaluated in a broad spectrum of autoimmune diseases in that many patients and in context of individual medications,” said study author Raoul Tibes, MD, PhD, of the Mayo Clinic in Phoenix, Arizona.

“Interestingly, there was no association with length of time on therapy and resulting myeloid neoplasm.”

Dr Tibes and his colleagues reported these findings in JAMA Oncology.

The researchers reviewed data on 40,011 patients with primary autoimmune disorders, such as lupus and rheumatoid arthritis, who were seen at 2 centers from January 1, 2004, to December 31, 2014.

There were 311 patients with MDS or AML, but only 86 met strict inclusion criteria. Fifty-five patients had MDS, 21 had de novo AML, and 10 had AML and a history of MDS.

The researchers collected detailed data on each patient’s drug exposures, treatment duration, and disease characteristics and compared this information to data from patients with autoimmune disorders who did not have MDS or AML.

This revealed that use of azathioprine sodium was more frequent in cases than controls, and azathioprine was significantly associated with an increased risk of MDS and AML. The odds ratio was 7.05 (P<0.001).

Other agents used showed a similar trend, but the results were not statistically significant. The odds ratios were 3.58 for cyclophosphamide and 2.73 for mitoxantrone hydrochloride.

The researchers said that, while these results are intriguing, they should not change or replace the clinical judgments, monitoring, and current standard treatments for patients with autoimmune diseases.

Despite its large size, this study had limitations, including its retrospective nature, the fact that many different autoimmune diseases were analyzed, and that the researchers only looked at cases of MDS and AML.

No definitive causal association was made between taking a particular drug and MDS or AML. The number of patients with autoimmune disease developing MDS or AML is still low overall, and no prediction for individual patients can be concluded from the study.

The researchers plan to perform molecular investigations into the genetic susceptibility for therapy-related myeloid neoplasms as the next phase of this research.

Azathioprine tablets

Results of a large, retrospective study suggest that taking azathioprine, a drug commonly used to treat autoimmune disease, may increase a person’s risk of developing myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML).

Researchers analyzed data on more than 40,000 patients with 27 common autoimmune diseases and found that azathioprine use was significantly associated with an increased risk of MDS and AML.

“Similar associations were already documented in case reports and case series but have never been evaluated in a broad spectrum of autoimmune diseases in that many patients and in context of individual medications,” said study author Raoul Tibes, MD, PhD, of the Mayo Clinic in Phoenix, Arizona.

“Interestingly, there was no association with length of time on therapy and resulting myeloid neoplasm.”

Dr Tibes and his colleagues reported these findings in JAMA Oncology.

The researchers reviewed data on 40,011 patients with primary autoimmune disorders, such as lupus and rheumatoid arthritis, who were seen at 2 centers from January 1, 2004, to December 31, 2014.

There were 311 patients with MDS or AML, but only 86 met strict inclusion criteria. Fifty-five patients had MDS, 21 had de novo AML, and 10 had AML and a history of MDS.

The researchers collected detailed data on each patient’s drug exposures, treatment duration, and disease characteristics and compared this information to data from patients with autoimmune disorders who did not have MDS or AML.

This revealed that use of azathioprine sodium was more frequent in cases than controls, and azathioprine was significantly associated with an increased risk of MDS and AML. The odds ratio was 7.05 (P<0.001).

Other agents used showed a similar trend, but the results were not statistically significant. The odds ratios were 3.58 for cyclophosphamide and 2.73 for mitoxantrone hydrochloride.

The researchers said that, while these results are intriguing, they should not change or replace the clinical judgments, monitoring, and current standard treatments for patients with autoimmune diseases.

Despite its large size, this study had limitations, including its retrospective nature, the fact that many different autoimmune diseases were analyzed, and that the researchers only looked at cases of MDS and AML.

No definitive causal association was made between taking a particular drug and MDS or AML. The number of patients with autoimmune disease developing MDS or AML is still low overall, and no prediction for individual patients can be concluded from the study.

The researchers plan to perform molecular investigations into the genetic susceptibility for therapy-related myeloid neoplasms as the next phase of this research.

Azathioprine tablets

Results of a large, retrospective study suggest that taking azathioprine, a drug commonly used to treat autoimmune disease, may increase a person’s risk of developing myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML).

Researchers analyzed data on more than 40,000 patients with 27 common autoimmune diseases and found that azathioprine use was significantly associated with an increased risk of MDS and AML.

“Similar associations were already documented in case reports and case series but have never been evaluated in a broad spectrum of autoimmune diseases in that many patients and in context of individual medications,” said study author Raoul Tibes, MD, PhD, of the Mayo Clinic in Phoenix, Arizona.

“Interestingly, there was no association with length of time on therapy and resulting myeloid neoplasm.”

Dr Tibes and his colleagues reported these findings in JAMA Oncology.

The researchers reviewed data on 40,011 patients with primary autoimmune disorders, such as lupus and rheumatoid arthritis, who were seen at 2 centers from January 1, 2004, to December 31, 2014.

There were 311 patients with MDS or AML, but only 86 met strict inclusion criteria. Fifty-five patients had MDS, 21 had de novo AML, and 10 had AML and a history of MDS.

The researchers collected detailed data on each patient’s drug exposures, treatment duration, and disease characteristics and compared this information to data from patients with autoimmune disorders who did not have MDS or AML.

This revealed that use of azathioprine sodium was more frequent in cases than controls, and azathioprine was significantly associated with an increased risk of MDS and AML. The odds ratio was 7.05 (P<0.001).

Other agents used showed a similar trend, but the results were not statistically significant. The odds ratios were 3.58 for cyclophosphamide and 2.73 for mitoxantrone hydrochloride.

The researchers said that, while these results are intriguing, they should not change or replace the clinical judgments, monitoring, and current standard treatments for patients with autoimmune diseases.

Despite its large size, this study had limitations, including its retrospective nature, the fact that many different autoimmune diseases were analyzed, and that the researchers only looked at cases of MDS and AML.

No definitive causal association was made between taking a particular drug and MDS or AML. The number of patients with autoimmune disease developing MDS or AML is still low overall, and no prediction for individual patients can be concluded from the study.

The researchers plan to perform molecular investigations into the genetic susceptibility for therapy-related myeloid neoplasms as the next phase of this research.

Leukemia stem cells
Image by Robert Paulson

The cell surface molecule CD99 occurs more frequently than normal on stem cells responsible for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), according to research published in Science Translational Medicine.

Building on this discovery, researchers designed anti-CD99 monoclonal antibodies (mAbs).

In vitro and in vivo experiments

showed that these mAbs can recognize

and destroy AML and MDS stem/progenitor cells.

“Our findings not only identify a new molecule expressed on stem cells that drive these human malignancies, but we show that antibodies against this target can directly kill human AML stem cells,” said study author Christopher Y. Park, MD, PhD, of NYU Langone Medical Center in New York, New York.

“While we still have important details to work out, CD99 is likely to be an exploitable therapeutic target for most AML and MDS patients, and we are working urgently to finalize a therapy for human testing.”

Dr Park and his colleagues first examined stem cell populations from 79 patients with AML and 24 with MDS. More than 80% of stem cells in both groups expressed high levels of CD99.

The levels were so high that leukemia stem cells could be cleanly separated from normal hematopoietic stem cells in AML samples.

Upon confirming that CD99 was abundant on AML and MDS stem cells, the researchers made several anti-CD99 mAbs and tested them in vitro and in mouse models.
 
The mAbs destroyed AML and MDS stem cells by causing a sudden spike in the activity of SRC family kinases—a group of proteins that are implicated in invasion, tumor progression, and metastasis in a variety of cancers.

However, the mAbs had minimal effects on normal hematopoietic stem cells.

“With the appropriate support, we believe we can rapidly determine the best antibodies for use in patients, produce them at the quality needed to verify our results, and apply for permission to begin clinical trials,” Dr Park said.

Leukemia stem cells
Image by Robert Paulson

The cell surface molecule CD99 occurs more frequently than normal on stem cells responsible for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), according to research published in Science Translational Medicine.

Building on this discovery, researchers designed anti-CD99 monoclonal antibodies (mAbs).

In vitro and in vivo experiments

showed that these mAbs can recognize

and destroy AML and MDS stem/progenitor cells.

“Our findings not only identify a new molecule expressed on stem cells that drive these human malignancies, but we show that antibodies against this target can directly kill human AML stem cells,” said study author Christopher Y. Park, MD, PhD, of NYU Langone Medical Center in New York, New York.

“While we still have important details to work out, CD99 is likely to be an exploitable therapeutic target for most AML and MDS patients, and we are working urgently to finalize a therapy for human testing.”

Dr Park and his colleagues first examined stem cell populations from 79 patients with AML and 24 with MDS. More than 80% of stem cells in both groups expressed high levels of CD99.

The levels were so high that leukemia stem cells could be cleanly separated from normal hematopoietic stem cells in AML samples.

Upon confirming that CD99 was abundant on AML and MDS stem cells, the researchers made several anti-CD99 mAbs and tested them in vitro and in mouse models.
 
The mAbs destroyed AML and MDS stem cells by causing a sudden spike in the activity of SRC family kinases—a group of proteins that are implicated in invasion, tumor progression, and metastasis in a variety of cancers.

However, the mAbs had minimal effects on normal hematopoietic stem cells.

“With the appropriate support, we believe we can rapidly determine the best antibodies for use in patients, produce them at the quality needed to verify our results, and apply for permission to begin clinical trials,” Dr Park said.

Leukemia stem cells
Image by Robert Paulson

The cell surface molecule CD99 occurs more frequently than normal on stem cells responsible for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), according to research published in Science Translational Medicine.

Building on this discovery, researchers designed anti-CD99 monoclonal antibodies (mAbs).

In vitro and in vivo experiments

showed that these mAbs can recognize

and destroy AML and MDS stem/progenitor cells.

“Our findings not only identify a new molecule expressed on stem cells that drive these human malignancies, but we show that antibodies against this target can directly kill human AML stem cells,” said study author Christopher Y. Park, MD, PhD, of NYU Langone Medical Center in New York, New York.

“While we still have important details to work out, CD99 is likely to be an exploitable therapeutic target for most AML and MDS patients, and we are working urgently to finalize a therapy for human testing.”

Dr Park and his colleagues first examined stem cell populations from 79 patients with AML and 24 with MDS. More than 80% of stem cells in both groups expressed high levels of CD99.

The levels were so high that leukemia stem cells could be cleanly separated from normal hematopoietic stem cells in AML samples.

Upon confirming that CD99 was abundant on AML and MDS stem cells, the researchers made several anti-CD99 mAbs and tested them in vitro and in mouse models.
 
The mAbs destroyed AML and MDS stem cells by causing a sudden spike in the activity of SRC family kinases—a group of proteins that are implicated in invasion, tumor progression, and metastasis in a variety of cancers.

However, the mAbs had minimal effects on normal hematopoietic stem cells.

“With the appropriate support, we believe we can rapidly determine the best antibodies for use in patients, produce them at the quality needed to verify our results, and apply for permission to begin clinical trials,” Dr Park said.

Red blood cells

Consuming an iron-fortified nutrition bar daily for a few months can fight anemia without producing side effects, according to research published in the American Journal of Clinical Nutrition.

Anemic

women in India who consumed an iron-fortified nutrition bar each day for 90 days

were much more likely to experience increases in hemoglobin and

hematocrit and to be cured of their anemia than women who did not consume

such bars.

Rajvi Mehta, a medical student at Duke University in Durham, North Carolina, developed the nutrition bars used in this study, known as GudNesS bars.

The bars are made with iron-rich, natural, local (to India), and culturally accepted ingredients. They contain the World Health Organization’s daily recommended dose of iron.

In 2011, Mehta worked with nutritionists and physicians in India to establish a social venture there called Let’s Be Well Red (LBWR) to begin large-scale production of the bars.

The study, conducted from March to August 2014 in Mumbai and Navi Mumbai, India, involved 179 anemic, non-pregnant participants of reproductive age (18-35) at 10 demographically diverse sites.

The sites were randomly placed in either a control group or an intervention group.

Women in the intervention group received 1 iron-fortified nutrition bar (containing 14 mg Fe) daily for 90 days, and women in the control group received nothing. Baseline characteristics were comparable between the groups.

Each group underwent 3 blood tests during the 90-day follow-up period—at 15 days, 45 days, and 90 days—to measure their hemoglobin and hematocrit.

Seventy-six percent of subjects (n=136) completed all follow-up assessments (65 intervention and 71 control subjects).

The primary outcomes were 90-day changes from baseline in hemoglobin concentrations and hematocrit percentages.

The researchers said the mean hemoglobin and hematocrit increases after 90 days were greater for the intervention group than the control group, at 1.4 g/dL and 2.7%, respectively.

And subjects in the intervention group had a much greater decrease in anemia than those in the control group. At 90 days, 29.2% of subjects in the intervention group still had anemia, compared to 98.6% of those in the control group. The odds ratio was 0.007.

The researchers said no side effects were reported.

“We are encouraged by the results of this study, which show a positive connection between consuming an iron-fortified nutrition bar and a reduction in anemia prevalence,” said study author Elizabeth Turner, PhD, of Duke University.

“It appears to be a practical and well-tolerated solution to a significant health challenge in India.”

Let’s Be Well Red is currently operating in 3 locations in India and produces 100,000 bars each year that it distributes throughout the country.

“Anemia is a debilitating condition that can have severe health consequences,” Mehta said. “I am thrilled that my colleagues and I were able to develop a solution that has proven to be effective among a high-risk population. Making an impact in global health has long been a goal of mine.”

Red blood cells

Consuming an iron-fortified nutrition bar daily for a few months can fight anemia without producing side effects, according to research published in the American Journal of Clinical Nutrition.

Anemic

women in India who consumed an iron-fortified nutrition bar each day for 90 days

were much more likely to experience increases in hemoglobin and

hematocrit and to be cured of their anemia than women who did not consume

such bars.

Rajvi Mehta, a medical student at Duke University in Durham, North Carolina, developed the nutrition bars used in this study, known as GudNesS bars.

The bars are made with iron-rich, natural, local (to India), and culturally accepted ingredients. They contain the World Health Organization’s daily recommended dose of iron.

In 2011, Mehta worked with nutritionists and physicians in India to establish a social venture there called Let’s Be Well Red (LBWR) to begin large-scale production of the bars.

The study, conducted from March to August 2014 in Mumbai and Navi Mumbai, India, involved 179 anemic, non-pregnant participants of reproductive age (18-35) at 10 demographically diverse sites.

The sites were randomly placed in either a control group or an intervention group.

Women in the intervention group received 1 iron-fortified nutrition bar (containing 14 mg Fe) daily for 90 days, and women in the control group received nothing. Baseline characteristics were comparable between the groups.

Each group underwent 3 blood tests during the 90-day follow-up period—at 15 days, 45 days, and 90 days—to measure their hemoglobin and hematocrit.

Seventy-six percent of subjects (n=136) completed all follow-up assessments (65 intervention and 71 control subjects).

The primary outcomes were 90-day changes from baseline in hemoglobin concentrations and hematocrit percentages.

The researchers said the mean hemoglobin and hematocrit increases after 90 days were greater for the intervention group than the control group, at 1.4 g/dL and 2.7%, respectively.

And subjects in the intervention group had a much greater decrease in anemia than those in the control group. At 90 days, 29.2% of subjects in the intervention group still had anemia, compared to 98.6% of those in the control group. The odds ratio was 0.007.

The researchers said no side effects were reported.

“We are encouraged by the results of this study, which show a positive connection between consuming an iron-fortified nutrition bar and a reduction in anemia prevalence,” said study author Elizabeth Turner, PhD, of Duke University.

“It appears to be a practical and well-tolerated solution to a significant health challenge in India.”

Let’s Be Well Red is currently operating in 3 locations in India and produces 100,000 bars each year that it distributes throughout the country.

“Anemia is a debilitating condition that can have severe health consequences,” Mehta said. “I am thrilled that my colleagues and I were able to develop a solution that has proven to be effective among a high-risk population. Making an impact in global health has long been a goal of mine.”

Red blood cells

Consuming an iron-fortified nutrition bar daily for a few months can fight anemia without producing side effects, according to research published in the American Journal of Clinical Nutrition.

Anemic

women in India who consumed an iron-fortified nutrition bar each day for 90 days

were much more likely to experience increases in hemoglobin and

hematocrit and to be cured of their anemia than women who did not consume

such bars.

Rajvi Mehta, a medical student at Duke University in Durham, North Carolina, developed the nutrition bars used in this study, known as GudNesS bars.

The bars are made with iron-rich, natural, local (to India), and culturally accepted ingredients. They contain the World Health Organization’s daily recommended dose of iron.

In 2011, Mehta worked with nutritionists and physicians in India to establish a social venture there called Let’s Be Well Red (LBWR) to begin large-scale production of the bars.

The study, conducted from March to August 2014 in Mumbai and Navi Mumbai, India, involved 179 anemic, non-pregnant participants of reproductive age (18-35) at 10 demographically diverse sites.

The sites were randomly placed in either a control group or an intervention group.

Women in the intervention group received 1 iron-fortified nutrition bar (containing 14 mg Fe) daily for 90 days, and women in the control group received nothing. Baseline characteristics were comparable between the groups.

Each group underwent 3 blood tests during the 90-day follow-up period—at 15 days, 45 days, and 90 days—to measure their hemoglobin and hematocrit.

Seventy-six percent of subjects (n=136) completed all follow-up assessments (65 intervention and 71 control subjects).

The primary outcomes were 90-day changes from baseline in hemoglobin concentrations and hematocrit percentages.

The researchers said the mean hemoglobin and hematocrit increases after 90 days were greater for the intervention group than the control group, at 1.4 g/dL and 2.7%, respectively.

And subjects in the intervention group had a much greater decrease in anemia than those in the control group. At 90 days, 29.2% of subjects in the intervention group still had anemia, compared to 98.6% of those in the control group. The odds ratio was 0.007.

The researchers said no side effects were reported.

“We are encouraged by the results of this study, which show a positive connection between consuming an iron-fortified nutrition bar and a reduction in anemia prevalence,” said study author Elizabeth Turner, PhD, of Duke University.

“It appears to be a practical and well-tolerated solution to a significant health challenge in India.”

Let’s Be Well Red is currently operating in 3 locations in India and produces 100,000 bars each year that it distributes throughout the country.

“Anemia is a debilitating condition that can have severe health consequences,” Mehta said. “I am thrilled that my colleagues and I were able to develop a solution that has proven to be effective among a high-risk population. Making an impact in global health has long been a goal of mine.”

Colony of iPSCs
Photo from Salk Institute

Researchers have created an induced pluripotent stem cell (iPSC) library intended to aid the study of sickle cell disease (SCD).

The library consists of iPSCs generated from blood samples taken from ethnically diverse SCD patients from around the world.

The researchers say these iPSCs can be used to create disease models, which may allow scientists to better understand how SCD occurs and develop and test new treatments for the disease.

As a complement to the library, the researchers also designed CRISPR/Cas gene editing tools to correct the sickle hemoglobin mutation.

The team described this work in Stem Cell Reports.

“Sickle cell disease affects millions of people worldwide and is an emerging global health burden,” said study author George Murphy, PhD, of the Center for Regenerative Medicine at Boston University School of Medicine in Massachusetts.

“iPSCs have the potential to revolutionize the way we study human development, model life-threatening diseases, and, eventually, treat patients.”

The researchers’ library includes SCD-specific iPSCs from patients of different ethnicities with different β-globin gene haplotypes and fetal hemoglobin levels.

The researchers generated 54 iPSC lines from blood samples collected from individuals of African American, Brazilian, and Saudi Arabian descent. Both genders were represented, as well as a range of ages (3 to 53 years of age).

Most of the cell lines in the library, along with accompanying genetic and hematologic data, are freely available via the WiCell website.

“In addition to the library, we’ve designed and are using gene editing tools to correct the sickle hemoglobin mutation using the stem cell lines,” said Gustavo Mostoslavsky, MD, PhD, also of the Center for Regenerative Medicine at Boston University School of Medicine.

“When coupled with corrected sickle cell disease-specific iPSCs, these tools could one day provide a functional cure for the disorder.”

Colony of iPSCs
Photo from Salk Institute

Researchers have created an induced pluripotent stem cell (iPSC) library intended to aid the study of sickle cell disease (SCD).

The library consists of iPSCs generated from blood samples taken from ethnically diverse SCD patients from around the world.

The researchers say these iPSCs can be used to create disease models, which may allow scientists to better understand how SCD occurs and develop and test new treatments for the disease.

As a complement to the library, the researchers also designed CRISPR/Cas gene editing tools to correct the sickle hemoglobin mutation.

The team described this work in Stem Cell Reports.

“Sickle cell disease affects millions of people worldwide and is an emerging global health burden,” said study author George Murphy, PhD, of the Center for Regenerative Medicine at Boston University School of Medicine in Massachusetts.

“iPSCs have the potential to revolutionize the way we study human development, model life-threatening diseases, and, eventually, treat patients.”

The researchers’ library includes SCD-specific iPSCs from patients of different ethnicities with different β-globin gene haplotypes and fetal hemoglobin levels.

The researchers generated 54 iPSC lines from blood samples collected from individuals of African American, Brazilian, and Saudi Arabian descent. Both genders were represented, as well as a range of ages (3 to 53 years of age).

Most of the cell lines in the library, along with accompanying genetic and hematologic data, are freely available via the WiCell website.

“In addition to the library, we’ve designed and are using gene editing tools to correct the sickle hemoglobin mutation using the stem cell lines,” said Gustavo Mostoslavsky, MD, PhD, also of the Center for Regenerative Medicine at Boston University School of Medicine.

“When coupled with corrected sickle cell disease-specific iPSCs, these tools could one day provide a functional cure for the disorder.”

Colony of iPSCs
Photo from Salk Institute

Researchers have created an induced pluripotent stem cell (iPSC) library intended to aid the study of sickle cell disease (SCD).

The library consists of iPSCs generated from blood samples taken from ethnically diverse SCD patients from around the world.

The researchers say these iPSCs can be used to create disease models, which may allow scientists to better understand how SCD occurs and develop and test new treatments for the disease.

As a complement to the library, the researchers also designed CRISPR/Cas gene editing tools to correct the sickle hemoglobin mutation.

The team described this work in Stem Cell Reports.

“Sickle cell disease affects millions of people worldwide and is an emerging global health burden,” said study author George Murphy, PhD, of the Center for Regenerative Medicine at Boston University School of Medicine in Massachusetts.

“iPSCs have the potential to revolutionize the way we study human development, model life-threatening diseases, and, eventually, treat patients.”

The researchers’ library includes SCD-specific iPSCs from patients of different ethnicities with different β-globin gene haplotypes and fetal hemoglobin levels.

The researchers generated 54 iPSC lines from blood samples collected from individuals of African American, Brazilian, and Saudi Arabian descent. Both genders were represented, as well as a range of ages (3 to 53 years of age).

Most of the cell lines in the library, along with accompanying genetic and hematologic data, are freely available via the WiCell website.

“In addition to the library, we’ve designed and are using gene editing tools to correct the sickle hemoglobin mutation using the stem cell lines,” said Gustavo Mostoslavsky, MD, PhD, also of the Center for Regenerative Medicine at Boston University School of Medicine.

“When coupled with corrected sickle cell disease-specific iPSCs, these tools could one day provide a functional cure for the disorder.”

Umbilical cord clamping
Photo by Meutia Chaerani
and Indradi Soemardjan

Delaying umbilical cord clamping by a few minutes can reduce the risk of anemia several months after birth, according to research published in JAMA Pediatrics.

A randomized clinical trial showed that delaying cord clamping by 3 minutes or more after birth—rather than clamping within 1 minute of birth—reduced the prevalence of anemia, iron deficiency, and iron deficiency anemia in infants at 8 months and 12 months of age.

Ola Andersson, MD, PhD, of Uppsala University in Uppsala, Sweden, and his colleagues conducted this research in Nepal, a country with a high prevalence of anemia.

The study included 540 infants—281 boys and 259 girls—with a mean gestational age of 39.2 weeks. Half of the subjects were randomized to delayed cord clamping (3 minutes or more after birth) or early cord clamping (within 1 minute of birth).

At 8 months of age, 78.5% of infants from the delayed clamping group and 69.6% from the early clamping group returned for blood sampling.

Results showed that infants in the delayed clamping group had higher levels of hemoglobin than infants in the early clamping group—10.4 g/dL and 10.2 g/dL, respectively (P=0.008).

Infants in the delayed clamping group also had a lower incidence of:

• Anemia (hemoglobin level <11.0 g/dL)—73.0% and 82.2%, respectively (P=0.01)
• Iron deficiency—22.2% and 38.1%, respectively (P<0.001)
• Iron deficiency anemia—19.3% and 33.3%, respectively (P<0.001).

The relative risk (RR) of anemia was 0.89, the RR of iron deficiency was 0.58, and the RR of iron deficiency anemia was 0.58.

Results were similar when the infants reached 12 months of age, although all the between-group differences were not statistically significant.

Again, infants in the delayed clamping group had higher levels of hemoglobin than infants in the early clamping group—10.3 g/dL and 10.1 g/dL, respectively (P=0.02).

And infants in the delayed clamping group had a lower incidence of:

• Anemia—77.8% and 85.9%, respectively (P=0.02)
• Iron deficiency—35.6% and 43%, respectively (P=0.09)
• Iron deficiency anemia—30.4% and 37.8%, respectively (P=0.08).

The RR of anemia was 0.91, the RR of iron deficiency was 0.83, and the RR of iron deficiency anemia was 0.80.

The researchers said this study shows that delayed cord clamping was an effective intervention to reduce anemia in a high-risk population, with minimal cost and without apparent adverse effects.

The team believes that, if this intervention were implemented on a global scale, this could translate to 5 million fewer infants with anemia at 8 months of age.

Umbilical cord clamping
Photo by Meutia Chaerani
and Indradi Soemardjan

Delaying umbilical cord clamping by a few minutes can reduce the risk of anemia several months after birth, according to research published in JAMA Pediatrics.

A randomized clinical trial showed that delaying cord clamping by 3 minutes or more after birth—rather than clamping within 1 minute of birth—reduced the prevalence of anemia, iron deficiency, and iron deficiency anemia in infants at 8 months and 12 months of age.

Ola Andersson, MD, PhD, of Uppsala University in Uppsala, Sweden, and his colleagues conducted this research in Nepal, a country with a high prevalence of anemia.

The study included 540 infants—281 boys and 259 girls—with a mean gestational age of 39.2 weeks. Half of the subjects were randomized to delayed cord clamping (3 minutes or more after birth) or early cord clamping (within 1 minute of birth).

At 8 months of age, 78.5% of infants from the delayed clamping group and 69.6% from the early clamping group returned for blood sampling.

Results showed that infants in the delayed clamping group had higher levels of hemoglobin than infants in the early clamping group—10.4 g/dL and 10.2 g/dL, respectively (P=0.008).

Infants in the delayed clamping group also had a lower incidence of:

• Anemia (hemoglobin level <11.0 g/dL)—73.0% and 82.2%, respectively (P=0.01)
• Iron deficiency—22.2% and 38.1%, respectively (P<0.001)
• Iron deficiency anemia—19.3% and 33.3%, respectively (P<0.001).

The relative risk (RR) of anemia was 0.89, the RR of iron deficiency was 0.58, and the RR of iron deficiency anemia was 0.58.

Results were similar when the infants reached 12 months of age, although all the between-group differences were not statistically significant.

Again, infants in the delayed clamping group had higher levels of hemoglobin than infants in the early clamping group—10.3 g/dL and 10.1 g/dL, respectively (P=0.02).

And infants in the delayed clamping group had a lower incidence of:

• Anemia—77.8% and 85.9%, respectively (P=0.02)
• Iron deficiency—35.6% and 43%, respectively (P=0.09)
• Iron deficiency anemia—30.4% and 37.8%, respectively (P=0.08).

The RR of anemia was 0.91, the RR of iron deficiency was 0.83, and the RR of iron deficiency anemia was 0.80.

The researchers said this study shows that delayed cord clamping was an effective intervention to reduce anemia in a high-risk population, with minimal cost and without apparent adverse effects.

The team believes that, if this intervention were implemented on a global scale, this could translate to 5 million fewer infants with anemia at 8 months of age.

Umbilical cord clamping
Photo by Meutia Chaerani
and Indradi Soemardjan

Delaying umbilical cord clamping by a few minutes can reduce the risk of anemia several months after birth, according to research published in JAMA Pediatrics.

A randomized clinical trial showed that delaying cord clamping by 3 minutes or more after birth—rather than clamping within 1 minute of birth—reduced the prevalence of anemia, iron deficiency, and iron deficiency anemia in infants at 8 months and 12 months of age.

Ola Andersson, MD, PhD, of Uppsala University in Uppsala, Sweden, and his colleagues conducted this research in Nepal, a country with a high prevalence of anemia.

The study included 540 infants—281 boys and 259 girls—with a mean gestational age of 39.2 weeks. Half of the subjects were randomized to delayed cord clamping (3 minutes or more after birth) or early cord clamping (within 1 minute of birth).

At 8 months of age, 78.5% of infants from the delayed clamping group and 69.6% from the early clamping group returned for blood sampling.

Results showed that infants in the delayed clamping group had higher levels of hemoglobin than infants in the early clamping group—10.4 g/dL and 10.2 g/dL, respectively (P=0.008).

Infants in the delayed clamping group also had a lower incidence of:

• Anemia (hemoglobin level <11.0 g/dL)—73.0% and 82.2%, respectively (P=0.01)
• Iron deficiency—22.2% and 38.1%, respectively (P<0.001)
• Iron deficiency anemia—19.3% and 33.3%, respectively (P<0.001).

The relative risk (RR) of anemia was 0.89, the RR of iron deficiency was 0.58, and the RR of iron deficiency anemia was 0.58.

Results were similar when the infants reached 12 months of age, although all the between-group differences were not statistically significant.

Again, infants in the delayed clamping group had higher levels of hemoglobin than infants in the early clamping group—10.3 g/dL and 10.1 g/dL, respectively (P=0.02).

And infants in the delayed clamping group had a lower incidence of:

• Anemia—77.8% and 85.9%, respectively (P=0.02)
• Iron deficiency—35.6% and 43%, respectively (P=0.09)
• Iron deficiency anemia—30.4% and 37.8%, respectively (P=0.08).

The RR of anemia was 0.91, the RR of iron deficiency was 0.83, and the RR of iron deficiency anemia was 0.80.

The researchers said this study shows that delayed cord clamping was an effective intervention to reduce anemia in a high-risk population, with minimal cost and without apparent adverse effects.

The team believes that, if this intervention were implemented on a global scale, this could translate to 5 million fewer infants with anemia at 8 months of age.