Anemia

Red blood cells

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to LentiGlobin® BB305 for the treatment of transfusion-dependent patients with beta-thalassemia major.

The product is created by inserting a functional human beta-globin gene into a patient’s hematopoietic stem cells ex vivo. The cells are returned to the patient via transplant.

The product is intended to treat sickle cell disease as well as beta-thalassemia major.

“The FDA’s breakthrough designation of LentiGlobin highlights that new therapies are needed for the treatment of patients with beta-thalassemia major, especially treatments with the potential to meaningfully reduce or liberate patients from transfusion dependence,” said David Davidson, MD, chief medical officer of bluebird bio, the company developing LentiGlobin.

“Our early clinical data investigating the use of LentiGlobin in patients with multiple genotypes of beta-thalassemia major . . . are very encouraging, and we remain on track to complete enrollment in the Northstar and HGB-205 studies in 2015.”

Early study results

The breakthrough designation is supported by data from the ongoing phase 1/2 Northstar (HGB-204) and HGB-205 studies. Findings in 8 subjects from both studies were presented at the 2014 ASH Annual Meeting.

As of December 1, five subjects with beta-thalassemia major had received LentiGlobin in the Northstar Study. The first 2 subjects were producing steadily increasing amounts of beta-T87Q-globin and were free of the need for transfusion for 5 months and 3 months, respectively.

Three additional subjects have received LentiGlobin as well, but researchers said it is too early to draw any meaningful conclusions on clinical efficacy.

As of December 1, two subjects with beta-thalassemia major received LentiGlobin as part of the HGB-205 study. Both achieved rapid transfusion independence with near-normal hemoglobin levels. And they were free from the need for transfusions for 12 months and 9 months, respectively.

The third treated subject, the first individual with sickle cell disease ever to be treated with gene therapy, has achieved neutrophil engraftment. But researchers said it is too early to draw any meaningful conclusions on clinical efficacy.

About breakthrough designation

The FDA’s breakthrough therapy designation is intended to expedite the development and review of a drug candidate intended to treat a serious or life-threatening condition.

For a drug to gain the designation, preliminary clinical evidence must suggest the drug could offer substantial improvement over existing therapies on one or more clinically significant endpoints.

The benefits of breakthrough designation include the same benefits as fast track designation (priority review, rolling review, etc.), plus an organizational commitment involving the FDA’s senior managers with more intensive guidance from the FDA.

Breakthrough therapy designation does not change the standards for approval.

Red blood cells

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to LentiGlobin® BB305 for the treatment of transfusion-dependent patients with beta-thalassemia major.

The product is created by inserting a functional human beta-globin gene into a patient’s hematopoietic stem cells ex vivo. The cells are returned to the patient via transplant.

The product is intended to treat sickle cell disease as well as beta-thalassemia major.

“The FDA’s breakthrough designation of LentiGlobin highlights that new therapies are needed for the treatment of patients with beta-thalassemia major, especially treatments with the potential to meaningfully reduce or liberate patients from transfusion dependence,” said David Davidson, MD, chief medical officer of bluebird bio, the company developing LentiGlobin.

“Our early clinical data investigating the use of LentiGlobin in patients with multiple genotypes of beta-thalassemia major . . . are very encouraging, and we remain on track to complete enrollment in the Northstar and HGB-205 studies in 2015.”

Early study results

The breakthrough designation is supported by data from the ongoing phase 1/2 Northstar (HGB-204) and HGB-205 studies. Findings in 8 subjects from both studies were presented at the 2014 ASH Annual Meeting.

As of December 1, five subjects with beta-thalassemia major had received LentiGlobin in the Northstar Study. The first 2 subjects were producing steadily increasing amounts of beta-T87Q-globin and were free of the need for transfusion for 5 months and 3 months, respectively.

Three additional subjects have received LentiGlobin as well, but researchers said it is too early to draw any meaningful conclusions on clinical efficacy.

As of December 1, two subjects with beta-thalassemia major received LentiGlobin as part of the HGB-205 study. Both achieved rapid transfusion independence with near-normal hemoglobin levels. And they were free from the need for transfusions for 12 months and 9 months, respectively.

The third treated subject, the first individual with sickle cell disease ever to be treated with gene therapy, has achieved neutrophil engraftment. But researchers said it is too early to draw any meaningful conclusions on clinical efficacy.

About breakthrough designation

The FDA’s breakthrough therapy designation is intended to expedite the development and review of a drug candidate intended to treat a serious or life-threatening condition.

For a drug to gain the designation, preliminary clinical evidence must suggest the drug could offer substantial improvement over existing therapies on one or more clinically significant endpoints.

The benefits of breakthrough designation include the same benefits as fast track designation (priority review, rolling review, etc.), plus an organizational commitment involving the FDA’s senior managers with more intensive guidance from the FDA.

Breakthrough therapy designation does not change the standards for approval.

Red blood cells

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to LentiGlobin® BB305 for the treatment of transfusion-dependent patients with beta-thalassemia major.

The product is created by inserting a functional human beta-globin gene into a patient’s hematopoietic stem cells ex vivo. The cells are returned to the patient via transplant.

The product is intended to treat sickle cell disease as well as beta-thalassemia major.

“The FDA’s breakthrough designation of LentiGlobin highlights that new therapies are needed for the treatment of patients with beta-thalassemia major, especially treatments with the potential to meaningfully reduce or liberate patients from transfusion dependence,” said David Davidson, MD, chief medical officer of bluebird bio, the company developing LentiGlobin.

“Our early clinical data investigating the use of LentiGlobin in patients with multiple genotypes of beta-thalassemia major . . . are very encouraging, and we remain on track to complete enrollment in the Northstar and HGB-205 studies in 2015.”

Early study results

The breakthrough designation is supported by data from the ongoing phase 1/2 Northstar (HGB-204) and HGB-205 studies. Findings in 8 subjects from both studies were presented at the 2014 ASH Annual Meeting.

As of December 1, five subjects with beta-thalassemia major had received LentiGlobin in the Northstar Study. The first 2 subjects were producing steadily increasing amounts of beta-T87Q-globin and were free of the need for transfusion for 5 months and 3 months, respectively.

Three additional subjects have received LentiGlobin as well, but researchers said it is too early to draw any meaningful conclusions on clinical efficacy.

As of December 1, two subjects with beta-thalassemia major received LentiGlobin as part of the HGB-205 study. Both achieved rapid transfusion independence with near-normal hemoglobin levels. And they were free from the need for transfusions for 12 months and 9 months, respectively.

The third treated subject, the first individual with sickle cell disease ever to be treated with gene therapy, has achieved neutrophil engraftment. But researchers said it is too early to draw any meaningful conclusions on clinical efficacy.

About breakthrough designation

The FDA’s breakthrough therapy designation is intended to expedite the development and review of a drug candidate intended to treat a serious or life-threatening condition.

For a drug to gain the designation, preliminary clinical evidence must suggest the drug could offer substantial improvement over existing therapies on one or more clinically significant endpoints.

The benefits of breakthrough designation include the same benefits as fast track designation (priority review, rolling review, etc.), plus an organizational commitment involving the FDA’s senior managers with more intensive guidance from the FDA.

Breakthrough therapy designation does not change the standards for approval.

Hematopoietic stem cells

in the bone marrow

Two new studies have revealed elements that are key to hematopoietic stem and progenitor cell (HSPC) mobilization.

In one study, investigators discovered that elevated levels of the peptide hormone angiotensin II increases HSPC mobilization in the context of vasculopathy and sickle cell disease (SCD).

In the other study, researchers found that p62, an autophagy regulator and signal organizer, is required to maintain HSPC retention in the bone marrow.

Jose Cancelas, MD, PhD, of the University of Cincinnati College of Medicine in Ohio, is the corresponding author on both studies.

In the first paper, published in Nature Communications, Dr Cancelas and his colleagues noted that patients with vasculopathies have an increase in circulating HSPCs.

“This phenomenon may represent a stress response contributing to vascular damage repair,” he said. “So the question becomes, how can we learn from these patients?”

Using mouse models of vasculopathy and vasculopathy-associated SCD, Dr Cancelas and his colleagues showed that acute and chronic elevated levels of angiotensin II resulted in an increased pool of HSPCs.

And when the researchers administered anti-angiotensin therapy, the pool of HSPCs decreased in mice and humans with SCD.

“These results indicate a new role for angiotensin in hematopoietic stem and progenitor cell trafficking under pathological conditions and define the hematopoietic consequences of anti-angiotensin therapy in vascular disease and sickle cell disease,” Dr Cancelas said.

“Every year, millions of patients receive anti-angiotensin therapies due to the harmful effects associated with chronic hyperangiotensinemia in cardiac, renal, or liver failure. Our study shows that this anti-angiotensin therapy modulates the levels of circulating stem cells and progenitors.”

In the second paper, published in Cell Reports, Dr Cancelas and his colleagues examined the role that p62 plays in HSPC mobilization.

The investigators found that, when p62 is lost in osteoblasts, mice develop a condition similar to osteoporosis in humans.

The osteoblasts cannot degrade inflammatory signals coming from macrophages. And as a consequence, the deficient osteoblasts secrete inflammatory signals that impair the retention of HSPCs in the bone marrow and allow their escape to the circulation.

Specifically, the team found that macrophages activate osteoblastic NF-kB, which results in osteopenia and HSPC egress. And p62 negatively regulates osteoblastic NF-kB activation.

Dr Cancelas noted that patients with inflammatory diseases often have osteopenia. So this research may provide insight into that phenomenon and help explain why patients with chronic inflammatory diseases have higher levels of circulating HSPCs.

Hematopoietic stem cells

in the bone marrow

Two new studies have revealed elements that are key to hematopoietic stem and progenitor cell (HSPC) mobilization.

In one study, investigators discovered that elevated levels of the peptide hormone angiotensin II increases HSPC mobilization in the context of vasculopathy and sickle cell disease (SCD).

In the other study, researchers found that p62, an autophagy regulator and signal organizer, is required to maintain HSPC retention in the bone marrow.

Jose Cancelas, MD, PhD, of the University of Cincinnati College of Medicine in Ohio, is the corresponding author on both studies.

In the first paper, published in Nature Communications, Dr Cancelas and his colleagues noted that patients with vasculopathies have an increase in circulating HSPCs.

“This phenomenon may represent a stress response contributing to vascular damage repair,” he said. “So the question becomes, how can we learn from these patients?”

Using mouse models of vasculopathy and vasculopathy-associated SCD, Dr Cancelas and his colleagues showed that acute and chronic elevated levels of angiotensin II resulted in an increased pool of HSPCs.

And when the researchers administered anti-angiotensin therapy, the pool of HSPCs decreased in mice and humans with SCD.

“These results indicate a new role for angiotensin in hematopoietic stem and progenitor cell trafficking under pathological conditions and define the hematopoietic consequences of anti-angiotensin therapy in vascular disease and sickle cell disease,” Dr Cancelas said.

“Every year, millions of patients receive anti-angiotensin therapies due to the harmful effects associated with chronic hyperangiotensinemia in cardiac, renal, or liver failure. Our study shows that this anti-angiotensin therapy modulates the levels of circulating stem cells and progenitors.”

In the second paper, published in Cell Reports, Dr Cancelas and his colleagues examined the role that p62 plays in HSPC mobilization.

The investigators found that, when p62 is lost in osteoblasts, mice develop a condition similar to osteoporosis in humans.

The osteoblasts cannot degrade inflammatory signals coming from macrophages. And as a consequence, the deficient osteoblasts secrete inflammatory signals that impair the retention of HSPCs in the bone marrow and allow their escape to the circulation.

Specifically, the team found that macrophages activate osteoblastic NF-kB, which results in osteopenia and HSPC egress. And p62 negatively regulates osteoblastic NF-kB activation.

Dr Cancelas noted that patients with inflammatory diseases often have osteopenia. So this research may provide insight into that phenomenon and help explain why patients with chronic inflammatory diseases have higher levels of circulating HSPCs.

Hematopoietic stem cells

in the bone marrow

Two new studies have revealed elements that are key to hematopoietic stem and progenitor cell (HSPC) mobilization.

In one study, investigators discovered that elevated levels of the peptide hormone angiotensin II increases HSPC mobilization in the context of vasculopathy and sickle cell disease (SCD).

In the other study, researchers found that p62, an autophagy regulator and signal organizer, is required to maintain HSPC retention in the bone marrow.

Jose Cancelas, MD, PhD, of the University of Cincinnati College of Medicine in Ohio, is the corresponding author on both studies.

In the first paper, published in Nature Communications, Dr Cancelas and his colleagues noted that patients with vasculopathies have an increase in circulating HSPCs.

“This phenomenon may represent a stress response contributing to vascular damage repair,” he said. “So the question becomes, how can we learn from these patients?”

Using mouse models of vasculopathy and vasculopathy-associated SCD, Dr Cancelas and his colleagues showed that acute and chronic elevated levels of angiotensin II resulted in an increased pool of HSPCs.

And when the researchers administered anti-angiotensin therapy, the pool of HSPCs decreased in mice and humans with SCD.

“These results indicate a new role for angiotensin in hematopoietic stem and progenitor cell trafficking under pathological conditions and define the hematopoietic consequences of anti-angiotensin therapy in vascular disease and sickle cell disease,” Dr Cancelas said.

“Every year, millions of patients receive anti-angiotensin therapies due to the harmful effects associated with chronic hyperangiotensinemia in cardiac, renal, or liver failure. Our study shows that this anti-angiotensin therapy modulates the levels of circulating stem cells and progenitors.”

In the second paper, published in Cell Reports, Dr Cancelas and his colleagues examined the role that p62 plays in HSPC mobilization.

The investigators found that, when p62 is lost in osteoblasts, mice develop a condition similar to osteoporosis in humans.

The osteoblasts cannot degrade inflammatory signals coming from macrophages. And as a consequence, the deficient osteoblasts secrete inflammatory signals that impair the retention of HSPCs in the bone marrow and allow their escape to the circulation.

Specifically, the team found that macrophages activate osteoblastic NF-kB, which results in osteopenia and HSPC egress. And p62 negatively regulates osteoblastic NF-kB activation.

Dr Cancelas noted that patients with inflammatory diseases often have osteopenia. So this research may provide insight into that phenomenon and help explain why patients with chronic inflammatory diseases have higher levels of circulating HSPCs.

Prescription drugs

Credit: CDC

Several hematology drugs approved by the US Food and Drug Administration (FDA) have recently undergone label changes to reflect newly reported adverse events.

Changes have been made to the labels for the JAK1/2 inhibitor ruxolitinib (Jakafi), the anti-CD20 monoclonal antibody obinutuzumab (Gazyva), the factor Xa inhibitor rivaroxaban (Xarelto), and the hematopoietic stem cell mobilizer plerixafor (Mozobil).

Plerixafor

Plerixafor is FDA-approved for use in combination with granulocyte-colony stimulating factor to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin lymphoma and multiple myeloma.

The product’s label was changed to include a new entry under the “Adverse Reactions” heading. Postmarketing experience suggested the drug may cause abnormal dreams and nightmares.

Rivaroxaban

Rivaroxaban is a factor Xa inhibitor that’s FDA-approved to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), to reduce the risk of recurrent DVT and PE, and to prevent DVT, which may lead to PE, in patients undergoing knee or hip replacement surgery.

Postmarketing experience has led to two changes to the “Adverse Reactions” section of rivaroxaban’s label. Thrombocytopenia has been added as an adverse reaction, and the term “cytolytic hepatitis” has been replaced with “hepatitis (including hepatocellular injury).”

Obinutuzumab

Obinutuzumab is a CD20-directed cytolytic antibody that is FDA-approved in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia.

The “Warnings and Precautions” section of obinutuzumab’s label has been changed to reflect that fatal infections have been reported in patients who received the drug.

The label has also been changed to coincide with changes in trial data. The label now states that obinutuzumab caused grade 3 or 4 neutropenia in 33% of patients and grade 3 or 4 thrombocytopenia in 10% of patients.

Ruxolitinib

Ruxolitinib is a JAK1/JAK2 inhibitor that’s FDA-approved to treat patients with polycythemia vera (PV) who cannot tolerate or don’t respond to hydroxyurea, as well as patients with intermediate or high-risk myelofibrosis.

Ruxolitinib’s label now includes a warning that symptoms of myeloproliferative neoplasms may return about a week after discontinuing treatment. The label also advises healthcare professionals to discourage patients form interrupting or discontinuing ruxolitinib without consulting their physician.

In addition, a warning about the risk of non-melanoma skin cancer associated with ruxolitinib, as well as advice for informing patients of this risk, have been added to ruxolitinib’s label.

The label has undergone significant changes in sections 6.1, “Clinical Trials Experience in Myelofibrosis” and 6.2 “Clinical Trial Experience in Polycythemia Vera.” It now includes additional information on the risk of thrombocytopenia, anemia, and neutropenia.

Under the “Special Populations” heading, recommendations were added to reduce the drug’s dose in patients with PV and moderate or severe renal impairment, as well as PV patients with hepatic impairment.

Prescription drugs

Credit: CDC

Several hematology drugs approved by the US Food and Drug Administration (FDA) have recently undergone label changes to reflect newly reported adverse events.

Changes have been made to the labels for the JAK1/2 inhibitor ruxolitinib (Jakafi), the anti-CD20 monoclonal antibody obinutuzumab (Gazyva), the factor Xa inhibitor rivaroxaban (Xarelto), and the hematopoietic stem cell mobilizer plerixafor (Mozobil).

Plerixafor

Plerixafor is FDA-approved for use in combination with granulocyte-colony stimulating factor to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin lymphoma and multiple myeloma.

The product’s label was changed to include a new entry under the “Adverse Reactions” heading. Postmarketing experience suggested the drug may cause abnormal dreams and nightmares.

Rivaroxaban

Rivaroxaban is a factor Xa inhibitor that’s FDA-approved to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), to reduce the risk of recurrent DVT and PE, and to prevent DVT, which may lead to PE, in patients undergoing knee or hip replacement surgery.

Postmarketing experience has led to two changes to the “Adverse Reactions” section of rivaroxaban’s label. Thrombocytopenia has been added as an adverse reaction, and the term “cytolytic hepatitis” has been replaced with “hepatitis (including hepatocellular injury).”

Obinutuzumab

Obinutuzumab is a CD20-directed cytolytic antibody that is FDA-approved in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia.

The “Warnings and Precautions” section of obinutuzumab’s label has been changed to reflect that fatal infections have been reported in patients who received the drug.

The label has also been changed to coincide with changes in trial data. The label now states that obinutuzumab caused grade 3 or 4 neutropenia in 33% of patients and grade 3 or 4 thrombocytopenia in 10% of patients.

Ruxolitinib

Ruxolitinib is a JAK1/JAK2 inhibitor that’s FDA-approved to treat patients with polycythemia vera (PV) who cannot tolerate or don’t respond to hydroxyurea, as well as patients with intermediate or high-risk myelofibrosis.

Ruxolitinib’s label now includes a warning that symptoms of myeloproliferative neoplasms may return about a week after discontinuing treatment. The label also advises healthcare professionals to discourage patients form interrupting or discontinuing ruxolitinib without consulting their physician.

In addition, a warning about the risk of non-melanoma skin cancer associated with ruxolitinib, as well as advice for informing patients of this risk, have been added to ruxolitinib’s label.

The label has undergone significant changes in sections 6.1, “Clinical Trials Experience in Myelofibrosis” and 6.2 “Clinical Trial Experience in Polycythemia Vera.” It now includes additional information on the risk of thrombocytopenia, anemia, and neutropenia.

Under the “Special Populations” heading, recommendations were added to reduce the drug’s dose in patients with PV and moderate or severe renal impairment, as well as PV patients with hepatic impairment.

Prescription drugs

Credit: CDC

Several hematology drugs approved by the US Food and Drug Administration (FDA) have recently undergone label changes to reflect newly reported adverse events.

Changes have been made to the labels for the JAK1/2 inhibitor ruxolitinib (Jakafi), the anti-CD20 monoclonal antibody obinutuzumab (Gazyva), the factor Xa inhibitor rivaroxaban (Xarelto), and the hematopoietic stem cell mobilizer plerixafor (Mozobil).

Plerixafor

Plerixafor is FDA-approved for use in combination with granulocyte-colony stimulating factor to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin lymphoma and multiple myeloma.

The product’s label was changed to include a new entry under the “Adverse Reactions” heading. Postmarketing experience suggested the drug may cause abnormal dreams and nightmares.

Rivaroxaban

Rivaroxaban is a factor Xa inhibitor that’s FDA-approved to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), to reduce the risk of recurrent DVT and PE, and to prevent DVT, which may lead to PE, in patients undergoing knee or hip replacement surgery.

Postmarketing experience has led to two changes to the “Adverse Reactions” section of rivaroxaban’s label. Thrombocytopenia has been added as an adverse reaction, and the term “cytolytic hepatitis” has been replaced with “hepatitis (including hepatocellular injury).”

Obinutuzumab

Obinutuzumab is a CD20-directed cytolytic antibody that is FDA-approved in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia.

The “Warnings and Precautions” section of obinutuzumab’s label has been changed to reflect that fatal infections have been reported in patients who received the drug.

The label has also been changed to coincide with changes in trial data. The label now states that obinutuzumab caused grade 3 or 4 neutropenia in 33% of patients and grade 3 or 4 thrombocytopenia in 10% of patients.

Ruxolitinib

Ruxolitinib is a JAK1/JAK2 inhibitor that’s FDA-approved to treat patients with polycythemia vera (PV) who cannot tolerate or don’t respond to hydroxyurea, as well as patients with intermediate or high-risk myelofibrosis.

Ruxolitinib’s label now includes a warning that symptoms of myeloproliferative neoplasms may return about a week after discontinuing treatment. The label also advises healthcare professionals to discourage patients form interrupting or discontinuing ruxolitinib without consulting their physician.

In addition, a warning about the risk of non-melanoma skin cancer associated with ruxolitinib, as well as advice for informing patients of this risk, have been added to ruxolitinib’s label.

The label has undergone significant changes in sections 6.1, “Clinical Trials Experience in Myelofibrosis” and 6.2 “Clinical Trial Experience in Polycythemia Vera.” It now includes additional information on the risk of thrombocytopenia, anemia, and neutropenia.

Under the “Special Populations” heading, recommendations were added to reduce the drug’s dose in patients with PV and moderate or severe renal impairment, as well as PV patients with hepatic impairment.

Children in Kenya, where

one of the trials took place

Credit: Gabrielle Tenenbaum

Intermittent preventive antimalarial treatment (IPT) does not provide much benefit for anemic children living in malaria-endemic regions, results of a review indicate.

Researchers reviewed 6 randomized, controlled trials and found that IPT, doses of antimalarial drugs given at regular intervals in case children had contracted malaria, did lead to an improvement in hemoglobin levels.

But this did not translate to a reduction in the incidence of anemia or the rate of death and hospitalization compared to children who received placebo.

“While we did note small benefits in hemoglobin levels when treating anemic children with IPT, there was no detectable effect on the number of deaths or hospital admissions,” said review author Mwaka Athuman, of Ifakara Health Institute in Dodoma, Tanzania, Africa.

“However, 3 of the trials were carried out in areas where malaria transmission was low, so any estimate of the protective effect of IPT would be expected to be modest. The summary of the evidence will assist people forming policy guidance as to whether IPT is worthwhile and provide a basis for researchers to consider whether additional studies are needed.”

The researchers reported these findings in the Cochrane Database of Systematic Reviews.

The team reviewed 6 trials that included a total of 3847 children with anemia. Three trials were conducted in areas of low malaria endemicity and 3 in areas of moderate-to-high endemicity.

In all trials, there was a group of children who received IPT and a control group receiving placebo. In some trials, children also received iron supplements, and this was taken into consideration when the researchers analyzed the data.

Data from 4 of the trials showed that IPT did increase the mean change in hemoglobin levels from baseline to follow-up at 12 weeks—on average, by 0.32 g/dL. The reviewers dubbed this moderate-quality evidence.

Results from the same 4 trials showed that the mean hemoglobin at 12 weeks’ follow-up was, on average, 0.35 g/dL higher in the IPT group than in the placebo group. This was considered low-quality evidence.

Regardless of improvements in hemoglobin, there was no significant difference in the number of children who had anemia at 12 weeks. The median risk of anemia across 4 trials was 579 per 1000 in the placebo group and 561 per 1000 in the IPT group. This was considered moderate-quality evidence.

Similarly, there was no significant difference in the rate of death and hospitalization at 6 months between children who received IPT and those who received placebo.

The median risk of both events combined was 34 per 1000 in the placebo group and 31 per 1000 in the IPT group. This was based on data from 3 trials and was considered moderate-quality evidence.

For all of these outcomes, there was no significant difference between children who received iron and those who did not, and there was no difference between children living in regions of low malaria endemicity and those living in regions of moderate-to-high malaria endemicity.

Children in Kenya, where

one of the trials took place

Credit: Gabrielle Tenenbaum

Intermittent preventive antimalarial treatment (IPT) does not provide much benefit for anemic children living in malaria-endemic regions, results of a review indicate.

Researchers reviewed 6 randomized, controlled trials and found that IPT, doses of antimalarial drugs given at regular intervals in case children had contracted malaria, did lead to an improvement in hemoglobin levels.

But this did not translate to a reduction in the incidence of anemia or the rate of death and hospitalization compared to children who received placebo.

“While we did note small benefits in hemoglobin levels when treating anemic children with IPT, there was no detectable effect on the number of deaths or hospital admissions,” said review author Mwaka Athuman, of Ifakara Health Institute in Dodoma, Tanzania, Africa.

“However, 3 of the trials were carried out in areas where malaria transmission was low, so any estimate of the protective effect of IPT would be expected to be modest. The summary of the evidence will assist people forming policy guidance as to whether IPT is worthwhile and provide a basis for researchers to consider whether additional studies are needed.”

The researchers reported these findings in the Cochrane Database of Systematic Reviews.

The team reviewed 6 trials that included a total of 3847 children with anemia. Three trials were conducted in areas of low malaria endemicity and 3 in areas of moderate-to-high endemicity.

In all trials, there was a group of children who received IPT and a control group receiving placebo. In some trials, children also received iron supplements, and this was taken into consideration when the researchers analyzed the data.

Data from 4 of the trials showed that IPT did increase the mean change in hemoglobin levels from baseline to follow-up at 12 weeks—on average, by 0.32 g/dL. The reviewers dubbed this moderate-quality evidence.

Results from the same 4 trials showed that the mean hemoglobin at 12 weeks’ follow-up was, on average, 0.35 g/dL higher in the IPT group than in the placebo group. This was considered low-quality evidence.

Regardless of improvements in hemoglobin, there was no significant difference in the number of children who had anemia at 12 weeks. The median risk of anemia across 4 trials was 579 per 1000 in the placebo group and 561 per 1000 in the IPT group. This was considered moderate-quality evidence.

Similarly, there was no significant difference in the rate of death and hospitalization at 6 months between children who received IPT and those who received placebo.

The median risk of both events combined was 34 per 1000 in the placebo group and 31 per 1000 in the IPT group. This was based on data from 3 trials and was considered moderate-quality evidence.

For all of these outcomes, there was no significant difference between children who received iron and those who did not, and there was no difference between children living in regions of low malaria endemicity and those living in regions of moderate-to-high malaria endemicity.

Children in Kenya, where

one of the trials took place

Credit: Gabrielle Tenenbaum

Intermittent preventive antimalarial treatment (IPT) does not provide much benefit for anemic children living in malaria-endemic regions, results of a review indicate.

Researchers reviewed 6 randomized, controlled trials and found that IPT, doses of antimalarial drugs given at regular intervals in case children had contracted malaria, did lead to an improvement in hemoglobin levels.

But this did not translate to a reduction in the incidence of anemia or the rate of death and hospitalization compared to children who received placebo.

“While we did note small benefits in hemoglobin levels when treating anemic children with IPT, there was no detectable effect on the number of deaths or hospital admissions,” said review author Mwaka Athuman, of Ifakara Health Institute in Dodoma, Tanzania, Africa.

“However, 3 of the trials were carried out in areas where malaria transmission was low, so any estimate of the protective effect of IPT would be expected to be modest. The summary of the evidence will assist people forming policy guidance as to whether IPT is worthwhile and provide a basis for researchers to consider whether additional studies are needed.”

The researchers reported these findings in the Cochrane Database of Systematic Reviews.

The team reviewed 6 trials that included a total of 3847 children with anemia. Three trials were conducted in areas of low malaria endemicity and 3 in areas of moderate-to-high endemicity.

In all trials, there was a group of children who received IPT and a control group receiving placebo. In some trials, children also received iron supplements, and this was taken into consideration when the researchers analyzed the data.

Data from 4 of the trials showed that IPT did increase the mean change in hemoglobin levels from baseline to follow-up at 12 weeks—on average, by 0.32 g/dL. The reviewers dubbed this moderate-quality evidence.

Results from the same 4 trials showed that the mean hemoglobin at 12 weeks’ follow-up was, on average, 0.35 g/dL higher in the IPT group than in the placebo group. This was considered low-quality evidence.

Regardless of improvements in hemoglobin, there was no significant difference in the number of children who had anemia at 12 weeks. The median risk of anemia across 4 trials was 579 per 1000 in the placebo group and 561 per 1000 in the IPT group. This was considered moderate-quality evidence.

Similarly, there was no significant difference in the rate of death and hospitalization at 6 months between children who received IPT and those who received placebo.

The median risk of both events combined was 34 per 1000 in the placebo group and 31 per 1000 in the IPT group. This was based on data from 3 trials and was considered moderate-quality evidence.

For all of these outcomes, there was no significant difference between children who received iron and those who did not, and there was no difference between children living in regions of low malaria endemicity and those living in regions of moderate-to-high malaria endemicity.

Platelets for transfusion

Platelet transfusions may increase the risk of death in patients with platelet consumptive disorders, results of a large study suggest.

Investigators observed a 2-fold increase in the risk of death among patients with thrombotic thrombocytopenic purpura (TTP) who received platelet transfusions and a 5-fold increase among transfused patients with heparin-induced thrombocytopenia (HIT).

There was no increased risk among patients with immune thrombocytopenia (ITP), however.

Aaron Tobian, MD, PhD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland, and his colleagues reported these results in Blood. They were previously presented at the 2014 AABB Annual Meeting.

“Because these conditions are so rare, they’re difficult to study,” Dr Tobian noted. “There was some suggestion that transfusion may be harmful in these conditions, but it really was not known until now.”

“Our study is the first one to show that platelet transfusions are frequently administered to patients with ITP, HIT, and TTP, and that they’re associated with higher odds of arterial blood clots and mortality in TTP and HIT.”

For this study, Dr Tobian and his colleagues analyzed data from the Nationwide Inpatient Sample, a federal database that contains billing records for about 20% of all patients treated and discharged at about 1000 US community hospitals in 47 states.

The database contains information on about 8 million inpatient hospitalizations per year nationwide. The study covered the years 2007 to 2011.

During that time, there were 79,980 hospital admissions for ITP, 10,624 for TTP, and 6332 for HIT. Platelet transfusions were reported in 10.1% of hospitalizations for TTP, 7.1% for HIT, and 25.8% for ITP.

“Our analysis found no significantly increased risks from platelet transfusions in ITP,” said study author Ruchika Goel, MD, also of Johns Hopkins.

“But in TTP, a platelet transfusion increased the odds of a potentially lethal arterial blood clot more than 5-fold and doubled the odds of a heart attack.”

Specifically, in an age- and gender-adjusted analysis, the odds ratio (OR) for arterial thrombosis was 5.8, and the OR for acute myocardial infarction (AMI) was 2.0 in TTP patients who received platelet transfusions. The OR for stroke was 1.6, and the OR for venous thrombosis was 1.1.

Similarly, HIT patients had an increased risk of arterial thrombosis (OR=3.4) and AMI (OR=1.9) if they received a platelet transfusion. But they did not have an increased risk of venous thrombosis (OR=0.8) or stroke (OR=0.5).

Platelet transfusions among ITP patients were not significantly associated with venous thrombosis (OR=1.3), arterial thrombosis (OR=0.3), AMI (OR=1.3), or stroke (OR=1.3) after adjustment for age and gender.

The all-cause, in-hospital mortality rates were 8.8% for TTP patients, 3.4% for HIT patients, and 1.4% for ITP patients.

Patients with TTP and HIT had a significantly increased risk of all-cause mortality if they received platelet transfusions, with age- and gender-adjusted ORs of 2.0 and 5.2, respectively. But platelet transfusions were not significantly associated with mortality in ITP patients, with an OR of 1.1.

The investigators said they were surprised at the prevalence of platelet transfusions in this patient population, in spite of some practitioners’ concerns about the risks.

But Dr Tobian noted that, in some cases, doctors may not know a patient has a platelet disorder until they see the potentially deadly reaction to the transfusion. And in other cases, the transfusion may be used as a last resort.

He and his colleagues believe that, for patients with HIT and TTP, platelet transfusions should be reserved “only for severe, life-threatening bleeding refractory to other therapies or major surgery.”

Platelets for transfusion

Platelet transfusions may increase the risk of death in patients with platelet consumptive disorders, results of a large study suggest.

Investigators observed a 2-fold increase in the risk of death among patients with thrombotic thrombocytopenic purpura (TTP) who received platelet transfusions and a 5-fold increase among transfused patients with heparin-induced thrombocytopenia (HIT).

There was no increased risk among patients with immune thrombocytopenia (ITP), however.

Aaron Tobian, MD, PhD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland, and his colleagues reported these results in Blood. They were previously presented at the 2014 AABB Annual Meeting.

“Because these conditions are so rare, they’re difficult to study,” Dr Tobian noted. “There was some suggestion that transfusion may be harmful in these conditions, but it really was not known until now.”

“Our study is the first one to show that platelet transfusions are frequently administered to patients with ITP, HIT, and TTP, and that they’re associated with higher odds of arterial blood clots and mortality in TTP and HIT.”

For this study, Dr Tobian and his colleagues analyzed data from the Nationwide Inpatient Sample, a federal database that contains billing records for about 20% of all patients treated and discharged at about 1000 US community hospitals in 47 states.

The database contains information on about 8 million inpatient hospitalizations per year nationwide. The study covered the years 2007 to 2011.

During that time, there were 79,980 hospital admissions for ITP, 10,624 for TTP, and 6332 for HIT. Platelet transfusions were reported in 10.1% of hospitalizations for TTP, 7.1% for HIT, and 25.8% for ITP.

“Our analysis found no significantly increased risks from platelet transfusions in ITP,” said study author Ruchika Goel, MD, also of Johns Hopkins.

“But in TTP, a platelet transfusion increased the odds of a potentially lethal arterial blood clot more than 5-fold and doubled the odds of a heart attack.”

Specifically, in an age- and gender-adjusted analysis, the odds ratio (OR) for arterial thrombosis was 5.8, and the OR for acute myocardial infarction (AMI) was 2.0 in TTP patients who received platelet transfusions. The OR for stroke was 1.6, and the OR for venous thrombosis was 1.1.

Similarly, HIT patients had an increased risk of arterial thrombosis (OR=3.4) and AMI (OR=1.9) if they received a platelet transfusion. But they did not have an increased risk of venous thrombosis (OR=0.8) or stroke (OR=0.5).

Platelet transfusions among ITP patients were not significantly associated with venous thrombosis (OR=1.3), arterial thrombosis (OR=0.3), AMI (OR=1.3), or stroke (OR=1.3) after adjustment for age and gender.

The all-cause, in-hospital mortality rates were 8.8% for TTP patients, 3.4% for HIT patients, and 1.4% for ITP patients.

Patients with TTP and HIT had a significantly increased risk of all-cause mortality if they received platelet transfusions, with age- and gender-adjusted ORs of 2.0 and 5.2, respectively. But platelet transfusions were not significantly associated with mortality in ITP patients, with an OR of 1.1.

The investigators said they were surprised at the prevalence of platelet transfusions in this patient population, in spite of some practitioners’ concerns about the risks.

But Dr Tobian noted that, in some cases, doctors may not know a patient has a platelet disorder until they see the potentially deadly reaction to the transfusion. And in other cases, the transfusion may be used as a last resort.

He and his colleagues believe that, for patients with HIT and TTP, platelet transfusions should be reserved “only for severe, life-threatening bleeding refractory to other therapies or major surgery.”

Platelets for transfusion

Platelet transfusions may increase the risk of death in patients with platelet consumptive disorders, results of a large study suggest.

Investigators observed a 2-fold increase in the risk of death among patients with thrombotic thrombocytopenic purpura (TTP) who received platelet transfusions and a 5-fold increase among transfused patients with heparin-induced thrombocytopenia (HIT).

There was no increased risk among patients with immune thrombocytopenia (ITP), however.

Aaron Tobian, MD, PhD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland, and his colleagues reported these results in Blood. They were previously presented at the 2014 AABB Annual Meeting.

“Because these conditions are so rare, they’re difficult to study,” Dr Tobian noted. “There was some suggestion that transfusion may be harmful in these conditions, but it really was not known until now.”

“Our study is the first one to show that platelet transfusions are frequently administered to patients with ITP, HIT, and TTP, and that they’re associated with higher odds of arterial blood clots and mortality in TTP and HIT.”

For this study, Dr Tobian and his colleagues analyzed data from the Nationwide Inpatient Sample, a federal database that contains billing records for about 20% of all patients treated and discharged at about 1000 US community hospitals in 47 states.

The database contains information on about 8 million inpatient hospitalizations per year nationwide. The study covered the years 2007 to 2011.

During that time, there were 79,980 hospital admissions for ITP, 10,624 for TTP, and 6332 for HIT. Platelet transfusions were reported in 10.1% of hospitalizations for TTP, 7.1% for HIT, and 25.8% for ITP.

“Our analysis found no significantly increased risks from platelet transfusions in ITP,” said study author Ruchika Goel, MD, also of Johns Hopkins.

“But in TTP, a platelet transfusion increased the odds of a potentially lethal arterial blood clot more than 5-fold and doubled the odds of a heart attack.”

Specifically, in an age- and gender-adjusted analysis, the odds ratio (OR) for arterial thrombosis was 5.8, and the OR for acute myocardial infarction (AMI) was 2.0 in TTP patients who received platelet transfusions. The OR for stroke was 1.6, and the OR for venous thrombosis was 1.1.

Similarly, HIT patients had an increased risk of arterial thrombosis (OR=3.4) and AMI (OR=1.9) if they received a platelet transfusion. But they did not have an increased risk of venous thrombosis (OR=0.8) or stroke (OR=0.5).

Platelet transfusions among ITP patients were not significantly associated with venous thrombosis (OR=1.3), arterial thrombosis (OR=0.3), AMI (OR=1.3), or stroke (OR=1.3) after adjustment for age and gender.

The all-cause, in-hospital mortality rates were 8.8% for TTP patients, 3.4% for HIT patients, and 1.4% for ITP patients.

Patients with TTP and HIT had a significantly increased risk of all-cause mortality if they received platelet transfusions, with age- and gender-adjusted ORs of 2.0 and 5.2, respectively. But platelet transfusions were not significantly associated with mortality in ITP patients, with an OR of 1.1.

The investigators said they were surprised at the prevalence of platelet transfusions in this patient population, in spite of some practitioners’ concerns about the risks.

But Dr Tobian noted that, in some cases, doctors may not know a patient has a platelet disorder until they see the potentially deadly reaction to the transfusion. And in other cases, the transfusion may be used as a last resort.

He and his colleagues believe that, for patients with HIT and TTP, platelet transfusions should be reserved “only for severe, life-threatening bleeding refractory to other therapies or major surgery.”

Cord blood donation

Credit: NHS

The US Food and Drug Administration (FDA) has granted orphan designation to a cord blood product called NiCord for the treatment of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), Hodgkin lymphoma (HL), and myelodysplastic syndromes (MDS).

NiCord consists of cells from a single cord blood unit cultured in nicotinamide—a vitamin B derivative—and cytokines that are typically used for expansion—thrombopoietin, interleukin 6, FLT3 ligand, and stem cell factor.

The FDA’s orphan drug designation for NiCord coincides with the positive opinion of the European Medicines Agency’s (EMA’s) Committee for Orphan Medicinal Products regarding NiCord as a treatment for AML. Gamida Cell, the company developing NiCord, intends to file for orphan drug status with the EMA for other indications as well.

“Receipt of orphan drug status for NiCord in the US and Europe advances Gamida Cell’s commercialization plans a major step further, as both afford significant advantages,” said Yael Margolin, President and CEO of Gamida Cell.

Orphan drug designation provides various regulatory and economic benefits, including 7 years of market exclusivity upon product approval in the US and 10 years in the European Union.

Trials of NiCord

NiCord is currently being tested in a phase 1/2 study as an investigational therapeutic treatment for hematologic malignancies. In this study, NiCord is being used as the sole stem cell source.

In a previous study, presented at the 11th Annual International Cord Blood Symposium, researchers transplanted a NiCord unit and an unmanipulated cord blood unit in patients with ALL, AML, MDS, HL, or non-Hodgkin lymphoma.

A majority of patients in this small, phase 1/2 study achieved early platelet and neutrophil engraftment. And, in some patients, that engraftment persisted for 2 years.

Eight of the 11 patients enrolled achieved engraftment with the NiCord unit, and 2 engrafted with the unmanipulated cord blood unit. One patient had primary graft failure.

There were no adverse events attributable to the NiCord unit, but 4 patients developed grade 1-2 acute GVHD, and 1 patient developed limited chronic GVHD.

For more information on NiCord, visit the Gamida Cell website.

Cord blood donation

Credit: NHS

The US Food and Drug Administration (FDA) has granted orphan designation to a cord blood product called NiCord for the treatment of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), Hodgkin lymphoma (HL), and myelodysplastic syndromes (MDS).

NiCord consists of cells from a single cord blood unit cultured in nicotinamide—a vitamin B derivative—and cytokines that are typically used for expansion—thrombopoietin, interleukin 6, FLT3 ligand, and stem cell factor.

The FDA’s orphan drug designation for NiCord coincides with the positive opinion of the European Medicines Agency’s (EMA’s) Committee for Orphan Medicinal Products regarding NiCord as a treatment for AML. Gamida Cell, the company developing NiCord, intends to file for orphan drug status with the EMA for other indications as well.

“Receipt of orphan drug status for NiCord in the US and Europe advances Gamida Cell’s commercialization plans a major step further, as both afford significant advantages,” said Yael Margolin, President and CEO of Gamida Cell.

Orphan drug designation provides various regulatory and economic benefits, including 7 years of market exclusivity upon product approval in the US and 10 years in the European Union.

Trials of NiCord

NiCord is currently being tested in a phase 1/2 study as an investigational therapeutic treatment for hematologic malignancies. In this study, NiCord is being used as the sole stem cell source.

In a previous study, presented at the 11th Annual International Cord Blood Symposium, researchers transplanted a NiCord unit and an unmanipulated cord blood unit in patients with ALL, AML, MDS, HL, or non-Hodgkin lymphoma.

A majority of patients in this small, phase 1/2 study achieved early platelet and neutrophil engraftment. And, in some patients, that engraftment persisted for 2 years.

Eight of the 11 patients enrolled achieved engraftment with the NiCord unit, and 2 engrafted with the unmanipulated cord blood unit. One patient had primary graft failure.

There were no adverse events attributable to the NiCord unit, but 4 patients developed grade 1-2 acute GVHD, and 1 patient developed limited chronic GVHD.

For more information on NiCord, visit the Gamida Cell website.

Cord blood donation

Credit: NHS

The US Food and Drug Administration (FDA) has granted orphan designation to a cord blood product called NiCord for the treatment of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), Hodgkin lymphoma (HL), and myelodysplastic syndromes (MDS).

NiCord consists of cells from a single cord blood unit cultured in nicotinamide—a vitamin B derivative—and cytokines that are typically used for expansion—thrombopoietin, interleukin 6, FLT3 ligand, and stem cell factor.

The FDA’s orphan drug designation for NiCord coincides with the positive opinion of the European Medicines Agency’s (EMA’s) Committee for Orphan Medicinal Products regarding NiCord as a treatment for AML. Gamida Cell, the company developing NiCord, intends to file for orphan drug status with the EMA for other indications as well.

“Receipt of orphan drug status for NiCord in the US and Europe advances Gamida Cell’s commercialization plans a major step further, as both afford significant advantages,” said Yael Margolin, President and CEO of Gamida Cell.

Orphan drug designation provides various regulatory and economic benefits, including 7 years of market exclusivity upon product approval in the US and 10 years in the European Union.

Trials of NiCord

NiCord is currently being tested in a phase 1/2 study as an investigational therapeutic treatment for hematologic malignancies. In this study, NiCord is being used as the sole stem cell source.

In a previous study, presented at the 11th Annual International Cord Blood Symposium, researchers transplanted a NiCord unit and an unmanipulated cord blood unit in patients with ALL, AML, MDS, HL, or non-Hodgkin lymphoma.

A majority of patients in this small, phase 1/2 study achieved early platelet and neutrophil engraftment. And, in some patients, that engraftment persisted for 2 years.

Eight of the 11 patients enrolled achieved engraftment with the NiCord unit, and 2 engrafted with the unmanipulated cord blood unit. One patient had primary graft failure.

There were no adverse events attributable to the NiCord unit, but 4 patients developed grade 1-2 acute GVHD, and 1 patient developed limited chronic GVHD.

For more information on NiCord, visit the Gamida Cell website.

Blood for transfusion

Credit: UAB Hospital

The process of pathogen inactivation does not compromise the quality of red blood cells (RBCs), results of a phase 3 study suggest.

Researchers compared untreated RBCs and RBCs treated with the INTERCEPT Blood System, a pathogen inactivation system.

The two sets of RBCs, which were given to cardiovascular surgery patients with acute anemia, had comparable hemoglobin content and in vitro quality, according to Cerus Corporation, makers of the INTERCEPT system.

Cerus recently announced these results, and the researchers plan to submit data from this study for presentation at upcoming scientific congresses.

“In our prior US phase 3 study in a similar patient population, INTERCEPT red cells were shown to be noninferior to control red cells in 148 patients based on a composite endpoint of myocardial infarction, renal failure, and death,” said Laurence Corash, MD, Cerus’s chief medical officer.

“The data from the recent phase 3 study met the European criteria for red blood cell components for transfusion and demonstrated sufficient hemoglobin content and in vitro quality compared to untreated red cells. We believe that the successful results from this study, combined with data from the prior phase 3 study, support the safety and efficacy of the INTERCEPT RBC system for CE Mark registration.”

In the current trial, researchers evaluated the efficacy of the INTERCEPT system to process RBCs with quality and mean hemoglobin content (> 40 g) suitable to support transfusion according to the European Directorate for the Quality of Medicines.

The blood components were transfused in 51 cardiovascular surgery patients at 2 German trial sites. Patients undergoing procedures for coronary artery bypass grafting, valve repair, or combined procedures received transfusions during a 7-day treatment period that included the day of surgery and 6 days post-operatively.

The patients received either INTERCEPT-treated RBCs or control RBCs not treated for pathogen inactivation. RBC components for both clinical sites were manufactured at the German Red Cross blood center in Frankfurt, and the RBCs were stored for up to 35 days prior to transfusion.

The primary endpoint was the equivalence of mean hemoglobin content between INTERCEPT-treated RBCs and conventional RBCs. The mean hemoglobin content of INTERCEPT-treated RBCs on day 35 of storage (53.1 g) fell within the protocol-specified 5g equivalence margin, when compared to control RBCs (55.8 g).

The secondary efficacy endpoints also suggested INTERCEPT-treated RBCs were suitable for transfusion based on mean hematocrit of 60.4% (acceptance range: 55%-70%) and mean end-of-storage hemolysis rate of 0.28% (acceptance range < 0.8%).

There were no statistical differences in the adverse event rates between recipients of INTERCEPT-treated RBCs and control RBCs. There were no clinically relevant trends in severe or serious treatment-related adverse events by system organ class.

The observed adverse events were within the expected spectrum of comorbidity and mortality for patients of similar age and with advanced cardiovascular diseases undergoing cardiovascular surgery requiring RBC transfusion. And none of the patients exhibited an immune response to INTERCEPT-treated RBCs.

Blood for transfusion

Credit: UAB Hospital

The process of pathogen inactivation does not compromise the quality of red blood cells (RBCs), results of a phase 3 study suggest.

Researchers compared untreated RBCs and RBCs treated with the INTERCEPT Blood System, a pathogen inactivation system.

The two sets of RBCs, which were given to cardiovascular surgery patients with acute anemia, had comparable hemoglobin content and in vitro quality, according to Cerus Corporation, makers of the INTERCEPT system.

Cerus recently announced these results, and the researchers plan to submit data from this study for presentation at upcoming scientific congresses.

“In our prior US phase 3 study in a similar patient population, INTERCEPT red cells were shown to be noninferior to control red cells in 148 patients based on a composite endpoint of myocardial infarction, renal failure, and death,” said Laurence Corash, MD, Cerus’s chief medical officer.

“The data from the recent phase 3 study met the European criteria for red blood cell components for transfusion and demonstrated sufficient hemoglobin content and in vitro quality compared to untreated red cells. We believe that the successful results from this study, combined with data from the prior phase 3 study, support the safety and efficacy of the INTERCEPT RBC system for CE Mark registration.”

In the current trial, researchers evaluated the efficacy of the INTERCEPT system to process RBCs with quality and mean hemoglobin content (> 40 g) suitable to support transfusion according to the European Directorate for the Quality of Medicines.

The blood components were transfused in 51 cardiovascular surgery patients at 2 German trial sites. Patients undergoing procedures for coronary artery bypass grafting, valve repair, or combined procedures received transfusions during a 7-day treatment period that included the day of surgery and 6 days post-operatively.

The patients received either INTERCEPT-treated RBCs or control RBCs not treated for pathogen inactivation. RBC components for both clinical sites were manufactured at the German Red Cross blood center in Frankfurt, and the RBCs were stored for up to 35 days prior to transfusion.

The primary endpoint was the equivalence of mean hemoglobin content between INTERCEPT-treated RBCs and conventional RBCs. The mean hemoglobin content of INTERCEPT-treated RBCs on day 35 of storage (53.1 g) fell within the protocol-specified 5g equivalence margin, when compared to control RBCs (55.8 g).

The secondary efficacy endpoints also suggested INTERCEPT-treated RBCs were suitable for transfusion based on mean hematocrit of 60.4% (acceptance range: 55%-70%) and mean end-of-storage hemolysis rate of 0.28% (acceptance range < 0.8%).

There were no statistical differences in the adverse event rates between recipients of INTERCEPT-treated RBCs and control RBCs. There were no clinically relevant trends in severe or serious treatment-related adverse events by system organ class.

The observed adverse events were within the expected spectrum of comorbidity and mortality for patients of similar age and with advanced cardiovascular diseases undergoing cardiovascular surgery requiring RBC transfusion. And none of the patients exhibited an immune response to INTERCEPT-treated RBCs.

Blood for transfusion

Credit: UAB Hospital

The process of pathogen inactivation does not compromise the quality of red blood cells (RBCs), results of a phase 3 study suggest.

Researchers compared untreated RBCs and RBCs treated with the INTERCEPT Blood System, a pathogen inactivation system.

The two sets of RBCs, which were given to cardiovascular surgery patients with acute anemia, had comparable hemoglobin content and in vitro quality, according to Cerus Corporation, makers of the INTERCEPT system.

Cerus recently announced these results, and the researchers plan to submit data from this study for presentation at upcoming scientific congresses.

“In our prior US phase 3 study in a similar patient population, INTERCEPT red cells were shown to be noninferior to control red cells in 148 patients based on a composite endpoint of myocardial infarction, renal failure, and death,” said Laurence Corash, MD, Cerus’s chief medical officer.

“The data from the recent phase 3 study met the European criteria for red blood cell components for transfusion and demonstrated sufficient hemoglobin content and in vitro quality compared to untreated red cells. We believe that the successful results from this study, combined with data from the prior phase 3 study, support the safety and efficacy of the INTERCEPT RBC system for CE Mark registration.”

In the current trial, researchers evaluated the efficacy of the INTERCEPT system to process RBCs with quality and mean hemoglobin content (> 40 g) suitable to support transfusion according to the European Directorate for the Quality of Medicines.

The blood components were transfused in 51 cardiovascular surgery patients at 2 German trial sites. Patients undergoing procedures for coronary artery bypass grafting, valve repair, or combined procedures received transfusions during a 7-day treatment period that included the day of surgery and 6 days post-operatively.

The patients received either INTERCEPT-treated RBCs or control RBCs not treated for pathogen inactivation. RBC components for both clinical sites were manufactured at the German Red Cross blood center in Frankfurt, and the RBCs were stored for up to 35 days prior to transfusion.

The primary endpoint was the equivalence of mean hemoglobin content between INTERCEPT-treated RBCs and conventional RBCs. The mean hemoglobin content of INTERCEPT-treated RBCs on day 35 of storage (53.1 g) fell within the protocol-specified 5g equivalence margin, when compared to control RBCs (55.8 g).

The secondary efficacy endpoints also suggested INTERCEPT-treated RBCs were suitable for transfusion based on mean hematocrit of 60.4% (acceptance range: 55%-70%) and mean end-of-storage hemolysis rate of 0.28% (acceptance range < 0.8%).

There were no statistical differences in the adverse event rates between recipients of INTERCEPT-treated RBCs and control RBCs. There were no clinically relevant trends in severe or serious treatment-related adverse events by system organ class.

The observed adverse events were within the expected spectrum of comorbidity and mortality for patients of similar age and with advanced cardiovascular diseases undergoing cardiovascular surgery requiring RBC transfusion. And none of the patients exhibited an immune response to INTERCEPT-treated RBCs.

SAN FRANCISCO—Pharmaceutical-grade L-glutamine can reduce the risk of complications in patients with sickle cell disease (SCD), according to new research.

In a phase 3 study of more than 200 patients, those who received L-glutamine saw a reduction in sickle cell crises, hospitalizations, and the incidence of acute chest syndrome (ACS) when compared to patients who received placebo.

In addition, L-glutamine appeared to have a synergistic effect with hydroxyurea.

Yutaka Niihara, MD, of Emmaus Medical, Inc., in Torrance, California, presented these results at the 2014 ASH Annual Meeting (abstract 86*). Emmaus Medical produced the pharmaceutical-grade L-glutamine used in the study.

Dr Niihara noted that nicotinamide adenine dinucleotide (NAD) is an important physiological antioxidant in red blood cells. But in sickled red blood cells, NAD redox potential is significantly compromised.

So he and his colleagues hypothesized that glutamine, a precursor for NAD, can improve NAD redox potential and modify the destructive effect of increased oxidation and the pathophysiology of SCD. They also theorized that glutamine will decrease the frequency of vaso-occlusive crises.

To test their theories, the researchers enrolled 230 patients from 31 different sites on a phase 3 trial. Patients had sickle cell anemia (SS) or sickle B⁰ thalassemia. They were 5 years of age or older, and some were receiving hydroxyurea.

Patients were randomized 2:1 to receive L-glutamine at 0.3 g/kg twice daily (maximum 30 g/day) or placebo (maltodextrin) at 0.3 g/kg twice daily for 48 weeks. The researchers had discovered high variation in the quality of over-the-counter L-glutamine, so they used pharmaceutical-grade L-glutamine only.

In all, 152 patients received L-glutamine, and 78 received placebo. Demographics and baseline characteristics were similar between the two treatment arms.

The median age was 19 (range, 5-57) in the L-glutamine arm and 17 (range, 5-58) in the placebo arm. There were more females than males in both arms—52% and 57.7%, respectively. And most patients in both arms had sickle cell anemia—89.5% and 91%, respectively.

Safety and efficacy

Dr Niihara said there were no serious adverse events attributable to L-glutamine and no dose modifications due to toxicity.

There were more gastrointestinal events (such as constipation and flatulence) in the L-glutamine arm (8.6%) than in the placebo arm (5.2%). But there was no difference in other adverse events between the two arms.

The study’s primary endpoint was the frequency of painful sickle cell crises. Patients in the L-glutamine arm had 25% fewer crises than patients in the placebo arm (P=0.008).

In patients aged 18 and younger, the median number of sickle cell crises was 3 in the L-glutamine arm and 4 in the placebo arm (P<0.001). The numbers were the same in patients older than 18 (P<0.001) and among patients receiving hydroxyurea (P<0.001).

“Those patients, even though they were on hydroxyurea, they have shown improvements [with L-glutamine],” Dr Niihara said. “And it appears there is some synergistic effect . . ., certainly more than just an additive effect.”

Dr Niihara also noted that patients who received placebo took less than 2 months to experience a first sickle cell crisis, but, for patients on L-glutamine, it took almost 3 months before they had a first crisis. The time to a first crisis was a median of 87 days in the L-glutamine arm and 54 days in the placebo arm (P=0.010).

The study’s secondary endpoint was the frequency of hospitalizations. Compared to patients in the placebo arm, those in the L-glutamine arm had a 33% reduction in hospitalizations (P=0.005) and a 41% reduction in the length of hospital stay (P=0.022).

The researchers also looked at the incidence of ACS and found that L-glutamine was associated with a 58% reduction in ACS. The incidence was 26.9% in the placebo arm and 11.9% in the L-glutamine arm (P=0.006).

“We observed this cascade improvement [with L-glutamine],” Dr Niihara noted. “And what we mean [by that] is that, with glutamine, there is less chance of having painful crises, but if patients have to have crises, they have less chance of being hospitalized. And if they have to be hospitalized, their stays in the hospital are shorter. And, again, if they have to be hospitalized, there’s less chance of them going to the ICU with acute chest syndrome.”

Dr Niihara said the researchers’ next steps are to investigate L-glutamine in a clinical setting, in patients younger than 5 years old, in pregnant women, and as part of combination therapy.

*Information in the abstract differs from that presented at the meeting.

SAN FRANCISCO—Pharmaceutical-grade L-glutamine can reduce the risk of complications in patients with sickle cell disease (SCD), according to new research.

In a phase 3 study of more than 200 patients, those who received L-glutamine saw a reduction in sickle cell crises, hospitalizations, and the incidence of acute chest syndrome (ACS) when compared to patients who received placebo.

In addition, L-glutamine appeared to have a synergistic effect with hydroxyurea.

Yutaka Niihara, MD, of Emmaus Medical, Inc., in Torrance, California, presented these results at the 2014 ASH Annual Meeting (abstract 86*). Emmaus Medical produced the pharmaceutical-grade L-glutamine used in the study.

Dr Niihara noted that nicotinamide adenine dinucleotide (NAD) is an important physiological antioxidant in red blood cells. But in sickled red blood cells, NAD redox potential is significantly compromised.

So he and his colleagues hypothesized that glutamine, a precursor for NAD, can improve NAD redox potential and modify the destructive effect of increased oxidation and the pathophysiology of SCD. They also theorized that glutamine will decrease the frequency of vaso-occlusive crises.

To test their theories, the researchers enrolled 230 patients from 31 different sites on a phase 3 trial. Patients had sickle cell anemia (SS) or sickle B⁰ thalassemia. They were 5 years of age or older, and some were receiving hydroxyurea.

Patients were randomized 2:1 to receive L-glutamine at 0.3 g/kg twice daily (maximum 30 g/day) or placebo (maltodextrin) at 0.3 g/kg twice daily for 48 weeks. The researchers had discovered high variation in the quality of over-the-counter L-glutamine, so they used pharmaceutical-grade L-glutamine only.

In all, 152 patients received L-glutamine, and 78 received placebo. Demographics and baseline characteristics were similar between the two treatment arms.

The median age was 19 (range, 5-57) in the L-glutamine arm and 17 (range, 5-58) in the placebo arm. There were more females than males in both arms—52% and 57.7%, respectively. And most patients in both arms had sickle cell anemia—89.5% and 91%, respectively.

Safety and efficacy

Dr Niihara said there were no serious adverse events attributable to L-glutamine and no dose modifications due to toxicity.

There were more gastrointestinal events (such as constipation and flatulence) in the L-glutamine arm (8.6%) than in the placebo arm (5.2%). But there was no difference in other adverse events between the two arms.

The study’s primary endpoint was the frequency of painful sickle cell crises. Patients in the L-glutamine arm had 25% fewer crises than patients in the placebo arm (P=0.008).

In patients aged 18 and younger, the median number of sickle cell crises was 3 in the L-glutamine arm and 4 in the placebo arm (P<0.001). The numbers were the same in patients older than 18 (P<0.001) and among patients receiving hydroxyurea (P<0.001).

“Those patients, even though they were on hydroxyurea, they have shown improvements [with L-glutamine],” Dr Niihara said. “And it appears there is some synergistic effect . . ., certainly more than just an additive effect.”

Dr Niihara also noted that patients who received placebo took less than 2 months to experience a first sickle cell crisis, but, for patients on L-glutamine, it took almost 3 months before they had a first crisis. The time to a first crisis was a median of 87 days in the L-glutamine arm and 54 days in the placebo arm (P=0.010).

The study’s secondary endpoint was the frequency of hospitalizations. Compared to patients in the placebo arm, those in the L-glutamine arm had a 33% reduction in hospitalizations (P=0.005) and a 41% reduction in the length of hospital stay (P=0.022).

The researchers also looked at the incidence of ACS and found that L-glutamine was associated with a 58% reduction in ACS. The incidence was 26.9% in the placebo arm and 11.9% in the L-glutamine arm (P=0.006).

“We observed this cascade improvement [with L-glutamine],” Dr Niihara noted. “And what we mean [by that] is that, with glutamine, there is less chance of having painful crises, but if patients have to have crises, they have less chance of being hospitalized. And if they have to be hospitalized, their stays in the hospital are shorter. And, again, if they have to be hospitalized, there’s less chance of them going to the ICU with acute chest syndrome.”

Dr Niihara said the researchers’ next steps are to investigate L-glutamine in a clinical setting, in patients younger than 5 years old, in pregnant women, and as part of combination therapy.

*Information in the abstract differs from that presented at the meeting.

SAN FRANCISCO—Pharmaceutical-grade L-glutamine can reduce the risk of complications in patients with sickle cell disease (SCD), according to new research.

In a phase 3 study of more than 200 patients, those who received L-glutamine saw a reduction in sickle cell crises, hospitalizations, and the incidence of acute chest syndrome (ACS) when compared to patients who received placebo.

In addition, L-glutamine appeared to have a synergistic effect with hydroxyurea.

Yutaka Niihara, MD, of Emmaus Medical, Inc., in Torrance, California, presented these results at the 2014 ASH Annual Meeting (abstract 86*). Emmaus Medical produced the pharmaceutical-grade L-glutamine used in the study.

Dr Niihara noted that nicotinamide adenine dinucleotide (NAD) is an important physiological antioxidant in red blood cells. But in sickled red blood cells, NAD redox potential is significantly compromised.

So he and his colleagues hypothesized that glutamine, a precursor for NAD, can improve NAD redox potential and modify the destructive effect of increased oxidation and the pathophysiology of SCD. They also theorized that glutamine will decrease the frequency of vaso-occlusive crises.

To test their theories, the researchers enrolled 230 patients from 31 different sites on a phase 3 trial. Patients had sickle cell anemia (SS) or sickle B⁰ thalassemia. They were 5 years of age or older, and some were receiving hydroxyurea.

Patients were randomized 2:1 to receive L-glutamine at 0.3 g/kg twice daily (maximum 30 g/day) or placebo (maltodextrin) at 0.3 g/kg twice daily for 48 weeks. The researchers had discovered high variation in the quality of over-the-counter L-glutamine, so they used pharmaceutical-grade L-glutamine only.

In all, 152 patients received L-glutamine, and 78 received placebo. Demographics and baseline characteristics were similar between the two treatment arms.

The median age was 19 (range, 5-57) in the L-glutamine arm and 17 (range, 5-58) in the placebo arm. There were more females than males in both arms—52% and 57.7%, respectively. And most patients in both arms had sickle cell anemia—89.5% and 91%, respectively.

Safety and efficacy

Dr Niihara said there were no serious adverse events attributable to L-glutamine and no dose modifications due to toxicity.

There were more gastrointestinal events (such as constipation and flatulence) in the L-glutamine arm (8.6%) than in the placebo arm (5.2%). But there was no difference in other adverse events between the two arms.

The study’s primary endpoint was the frequency of painful sickle cell crises. Patients in the L-glutamine arm had 25% fewer crises than patients in the placebo arm (P=0.008).

In patients aged 18 and younger, the median number of sickle cell crises was 3 in the L-glutamine arm and 4 in the placebo arm (P<0.001). The numbers were the same in patients older than 18 (P<0.001) and among patients receiving hydroxyurea (P<0.001).

“Those patients, even though they were on hydroxyurea, they have shown improvements [with L-glutamine],” Dr Niihara said. “And it appears there is some synergistic effect . . ., certainly more than just an additive effect.”

Dr Niihara also noted that patients who received placebo took less than 2 months to experience a first sickle cell crisis, but, for patients on L-glutamine, it took almost 3 months before they had a first crisis. The time to a first crisis was a median of 87 days in the L-glutamine arm and 54 days in the placebo arm (P=0.010).

The study’s secondary endpoint was the frequency of hospitalizations. Compared to patients in the placebo arm, those in the L-glutamine arm had a 33% reduction in hospitalizations (P=0.005) and a 41% reduction in the length of hospital stay (P=0.022).

The researchers also looked at the incidence of ACS and found that L-glutamine was associated with a 58% reduction in ACS. The incidence was 26.9% in the placebo arm and 11.9% in the L-glutamine arm (P=0.006).

“We observed this cascade improvement [with L-glutamine],” Dr Niihara noted. “And what we mean [by that] is that, with glutamine, there is less chance of having painful crises, but if patients have to have crises, they have less chance of being hospitalized. And if they have to be hospitalized, their stays in the hospital are shorter. And, again, if they have to be hospitalized, there’s less chance of them going to the ICU with acute chest syndrome.”

Dr Niihara said the researchers’ next steps are to investigate L-glutamine in a clinical setting, in patients younger than 5 years old, in pregnant women, and as part of combination therapy.

*Information in the abstract differs from that presented at the meeting.

The US Food and Drug Administration (FDA) has approved tbo-filgrastim (Granix) injection for administration by patients and caregivers, allowing physicians to prescribe the drug for in-office or at-home use.

Tbo-filgrastim is a leukocyte growth factor used to reduce the duration of severe neutropenia in patients with non-myeloid malignancies who are receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.

The drug has been commercially available in the US since November 2013, but, at present, it can only be administered by a healthcare professional.

Teva Pharmaceutical Industries, Ltd., the company developing tbo-filgrastim, plans to launch the new syringe for administration by patients and caregivers in early 2015.

Clinical trials

Researchers evaluated tbo-filgrastim in 3 phase 3 trials of patients receiving myelosuppressive chemotherapy for breast cancer, lung cancer, and non-Hodgkin lymphoma (NHL).

In the NHL study, investigators compared tbo-filgrastim to filgrastim for the prevention of chemotherapy-induced neutropenia in 92 patients.

For cycle 1, patients were randomized to daily injections (subcutaneous 5 µg/kg/day) of tbo-filgrastim (n=63) or filgrastim (n=29) for at least 5 days and a maximum of 14 days. In subsequent cycles, all patients received tbo-filgrastim.

In cycle 1, the mean duration of severe neutropenia was 0.5 days in the tbo-filgrastim arm and 0.9 days in the filgrastim arm (P=0.1055). The incidence of febrile neutropenia was 11.1% and 20.7%, respectively (P=0.1232).

In the lung cancer trial, researchers compared tbo-filgrastim to filgrastim in 240 patients receiving platinum-based chemotherapy. In cycle 1, patients were randomized to daily injections (subcutaneous 5 µg/kg/d) of tbo-filgrastim  (n=160) or filgrastim (n=80) for at least 5 days and a maximum of 14 days. In subsequent cycles, all patients received tbo-filgrastim.

In cycle 1, the mean duration of severe neutropenia was 0.5 days in the tbo-filgrastim arm and 0.3 days in the filgrastim arm. There was no significant difference in the incidence of febrile neutropenia in cycle 1 between the two arms (P=0.2347).

In the breast cancer trial, investigators compared tbo-filgrastim to filgrastim or placebo in 348 patients receiving chemotherapy. Patients were randomized to daily injections (subcutaneous 5 µg/kg/day) for at least 5 days and a maximum of 14 days in each cycle of tbo-filgrastim (n=140), filgrastim (n=136), or placebo (n=72).

The mean duration of severe neutropenia in cycle 1 was 1.1 days in the tbo-filgrastim arm, 1.1 days in the filgrastim arm, and 3.9 days in the placebo arm.

In all the trials, bone pain was the most frequent treatment-emergent adverse event, occurring in at least 1% of patients treated with tbo-filgrastim at the recommended dose. The overall incidence of bone pain in cycle 1 was 3.4% for tbo-filgrastim, 1.4% for placebo, and 7.5% for filgrastim.

According to the drug’s prescribing information, tbo-filgrastim may pose a risk of splenic rupture, acute respiratory distress syndrome, serious allergic reactions, severe and sometimes fatal sickle cell crises, and capillary leak syndrome. The possibility that the drug acts as a growth factor for tumors cannot be excluded.

The US Food and Drug Administration (FDA) has approved tbo-filgrastim (Granix) injection for administration by patients and caregivers, allowing physicians to prescribe the drug for in-office or at-home use.

Tbo-filgrastim is a leukocyte growth factor used to reduce the duration of severe neutropenia in patients with non-myeloid malignancies who are receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.

The drug has been commercially available in the US since November 2013, but, at present, it can only be administered by a healthcare professional.

Teva Pharmaceutical Industries, Ltd., the company developing tbo-filgrastim, plans to launch the new syringe for administration by patients and caregivers in early 2015.

Clinical trials

Researchers evaluated tbo-filgrastim in 3 phase 3 trials of patients receiving myelosuppressive chemotherapy for breast cancer, lung cancer, and non-Hodgkin lymphoma (NHL).

In the NHL study, investigators compared tbo-filgrastim to filgrastim for the prevention of chemotherapy-induced neutropenia in 92 patients.

For cycle 1, patients were randomized to daily injections (subcutaneous 5 µg/kg/day) of tbo-filgrastim (n=63) or filgrastim (n=29) for at least 5 days and a maximum of 14 days. In subsequent cycles, all patients received tbo-filgrastim.

In cycle 1, the mean duration of severe neutropenia was 0.5 days in the tbo-filgrastim arm and 0.9 days in the filgrastim arm (P=0.1055). The incidence of febrile neutropenia was 11.1% and 20.7%, respectively (P=0.1232).

In the lung cancer trial, researchers compared tbo-filgrastim to filgrastim in 240 patients receiving platinum-based chemotherapy. In cycle 1, patients were randomized to daily injections (subcutaneous 5 µg/kg/d) of tbo-filgrastim  (n=160) or filgrastim (n=80) for at least 5 days and a maximum of 14 days. In subsequent cycles, all patients received tbo-filgrastim.

In cycle 1, the mean duration of severe neutropenia was 0.5 days in the tbo-filgrastim arm and 0.3 days in the filgrastim arm. There was no significant difference in the incidence of febrile neutropenia in cycle 1 between the two arms (P=0.2347).

In the breast cancer trial, investigators compared tbo-filgrastim to filgrastim or placebo in 348 patients receiving chemotherapy. Patients were randomized to daily injections (subcutaneous 5 µg/kg/day) for at least 5 days and a maximum of 14 days in each cycle of tbo-filgrastim (n=140), filgrastim (n=136), or placebo (n=72).

The mean duration of severe neutropenia in cycle 1 was 1.1 days in the tbo-filgrastim arm, 1.1 days in the filgrastim arm, and 3.9 days in the placebo arm.

In all the trials, bone pain was the most frequent treatment-emergent adverse event, occurring in at least 1% of patients treated with tbo-filgrastim at the recommended dose. The overall incidence of bone pain in cycle 1 was 3.4% for tbo-filgrastim, 1.4% for placebo, and 7.5% for filgrastim.

According to the drug’s prescribing information, tbo-filgrastim may pose a risk of splenic rupture, acute respiratory distress syndrome, serious allergic reactions, severe and sometimes fatal sickle cell crises, and capillary leak syndrome. The possibility that the drug acts as a growth factor for tumors cannot be excluded.

The US Food and Drug Administration (FDA) has approved tbo-filgrastim (Granix) injection for administration by patients and caregivers, allowing physicians to prescribe the drug for in-office or at-home use.

Tbo-filgrastim is a leukocyte growth factor used to reduce the duration of severe neutropenia in patients with non-myeloid malignancies who are receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.

The drug has been commercially available in the US since November 2013, but, at present, it can only be administered by a healthcare professional.

Teva Pharmaceutical Industries, Ltd., the company developing tbo-filgrastim, plans to launch the new syringe for administration by patients and caregivers in early 2015.

Clinical trials

Researchers evaluated tbo-filgrastim in 3 phase 3 trials of patients receiving myelosuppressive chemotherapy for breast cancer, lung cancer, and non-Hodgkin lymphoma (NHL).

In the NHL study, investigators compared tbo-filgrastim to filgrastim for the prevention of chemotherapy-induced neutropenia in 92 patients.

For cycle 1, patients were randomized to daily injections (subcutaneous 5 µg/kg/day) of tbo-filgrastim (n=63) or filgrastim (n=29) for at least 5 days and a maximum of 14 days. In subsequent cycles, all patients received tbo-filgrastim.

In cycle 1, the mean duration of severe neutropenia was 0.5 days in the tbo-filgrastim arm and 0.9 days in the filgrastim arm (P=0.1055). The incidence of febrile neutropenia was 11.1% and 20.7%, respectively (P=0.1232).

In the lung cancer trial, researchers compared tbo-filgrastim to filgrastim in 240 patients receiving platinum-based chemotherapy. In cycle 1, patients were randomized to daily injections (subcutaneous 5 µg/kg/d) of tbo-filgrastim  (n=160) or filgrastim (n=80) for at least 5 days and a maximum of 14 days. In subsequent cycles, all patients received tbo-filgrastim.

In cycle 1, the mean duration of severe neutropenia was 0.5 days in the tbo-filgrastim arm and 0.3 days in the filgrastim arm. There was no significant difference in the incidence of febrile neutropenia in cycle 1 between the two arms (P=0.2347).

In the breast cancer trial, investigators compared tbo-filgrastim to filgrastim or placebo in 348 patients receiving chemotherapy. Patients were randomized to daily injections (subcutaneous 5 µg/kg/day) for at least 5 days and a maximum of 14 days in each cycle of tbo-filgrastim (n=140), filgrastim (n=136), or placebo (n=72).

The mean duration of severe neutropenia in cycle 1 was 1.1 days in the tbo-filgrastim arm, 1.1 days in the filgrastim arm, and 3.9 days in the placebo arm.

In all the trials, bone pain was the most frequent treatment-emergent adverse event, occurring in at least 1% of patients treated with tbo-filgrastim at the recommended dose. The overall incidence of bone pain in cycle 1 was 3.4% for tbo-filgrastim, 1.4% for placebo, and 7.5% for filgrastim.

According to the drug’s prescribing information, tbo-filgrastim may pose a risk of splenic rupture, acute respiratory distress syndrome, serious allergic reactions, severe and sometimes fatal sickle cell crises, and capillary leak syndrome. The possibility that the drug acts as a growth factor for tumors cannot be excluded.

Blood sample on a slide

Credit: Максим Кукушкин

Researchers say they’ve developed a lens-free microscope that can detect the presence of cell-level abnormalities with the same accuracy as larger and more expensive optical microscopes.

The invention could lead to less expensive, more portable technology for performing examinations of tissue, blood, and other biomedical specimens, according to the researchers.

It may prove especially useful in remote areas and when large numbers of samples need to be examined quickly.

Aydogan Ozcan, PhD, of the University of California, Los Angeles, and his colleagues described their work with the microscope in Science Translational Medicine.

“This is a milestone in the work we’ve been doing,” Dr Ozcan said. “This is the first time tissue samples have been imaged in 3D using a lens-free, on-chip microscope.”

The device works by using a laser or light-emitting-diode to illuminate a tissue or blood sample that has been placed on a slide and inserted into the device. A sensor array on a microchip captures and records the pattern of shadows created by the sample.

The device processes these patterns as a series of holograms, forming 3-D images of the specimen and giving medical personnel a virtual depth-of-field view. An algorithm color codes the reconstructed images, making the contrasts in the samples more apparent than they would be in the holograms and making any abnormalities easier to detect.

Dr Ozcan’s team tested the device using blood samples containing sickle cell anemia, Pap smears that indicated cervical cancer, and tissue specimens containing cancerous breast cells.

In a blind test, a board-certified pathologist analyzed sets of specimen images that had been created by the lens-free technology and by conventional microscopes. The pathologist’s diagnoses using the lens-free microscopic images proved accurate 99% of the time.

Another benefit of the lens-free device, according to the researchers, is that it produces images that are several hundred times larger in area, or field of view, than those captured by conventional bright-field optical microscopes. This makes it possible to process specimens more quickly.

“While mobile healthcare has expanded rapidly with the growth of consumer electronics—cellphones in particular—pathology is still, by and large, constrained to advanced clinical laboratory settings,” Dr Ozcan said. “Accompanied by advances in its graphical user interface, this platform could scale up for use in clinical, biomedical, scientific, educational, and citizen-science applications, among others.”

Blood sample on a slide

Credit: Максим Кукушкин

Researchers say they’ve developed a lens-free microscope that can detect the presence of cell-level abnormalities with the same accuracy as larger and more expensive optical microscopes.

The invention could lead to less expensive, more portable technology for performing examinations of tissue, blood, and other biomedical specimens, according to the researchers.

It may prove especially useful in remote areas and when large numbers of samples need to be examined quickly.

Aydogan Ozcan, PhD, of the University of California, Los Angeles, and his colleagues described their work with the microscope in Science Translational Medicine.

“This is a milestone in the work we’ve been doing,” Dr Ozcan said. “This is the first time tissue samples have been imaged in 3D using a lens-free, on-chip microscope.”

The device works by using a laser or light-emitting-diode to illuminate a tissue or blood sample that has been placed on a slide and inserted into the device. A sensor array on a microchip captures and records the pattern of shadows created by the sample.

The device processes these patterns as a series of holograms, forming 3-D images of the specimen and giving medical personnel a virtual depth-of-field view. An algorithm color codes the reconstructed images, making the contrasts in the samples more apparent than they would be in the holograms and making any abnormalities easier to detect.

Dr Ozcan’s team tested the device using blood samples containing sickle cell anemia, Pap smears that indicated cervical cancer, and tissue specimens containing cancerous breast cells.

In a blind test, a board-certified pathologist analyzed sets of specimen images that had been created by the lens-free technology and by conventional microscopes. The pathologist’s diagnoses using the lens-free microscopic images proved accurate 99% of the time.

Another benefit of the lens-free device, according to the researchers, is that it produces images that are several hundred times larger in area, or field of view, than those captured by conventional bright-field optical microscopes. This makes it possible to process specimens more quickly.

“While mobile healthcare has expanded rapidly with the growth of consumer electronics—cellphones in particular—pathology is still, by and large, constrained to advanced clinical laboratory settings,” Dr Ozcan said. “Accompanied by advances in its graphical user interface, this platform could scale up for use in clinical, biomedical, scientific, educational, and citizen-science applications, among others.”

Blood sample on a slide

Credit: Максим Кукушкин

Researchers say they’ve developed a lens-free microscope that can detect the presence of cell-level abnormalities with the same accuracy as larger and more expensive optical microscopes.

The invention could lead to less expensive, more portable technology for performing examinations of tissue, blood, and other biomedical specimens, according to the researchers.

It may prove especially useful in remote areas and when large numbers of samples need to be examined quickly.

Aydogan Ozcan, PhD, of the University of California, Los Angeles, and his colleagues described their work with the microscope in Science Translational Medicine.

“This is a milestone in the work we’ve been doing,” Dr Ozcan said. “This is the first time tissue samples have been imaged in 3D using a lens-free, on-chip microscope.”

The device works by using a laser or light-emitting-diode to illuminate a tissue or blood sample that has been placed on a slide and inserted into the device. A sensor array on a microchip captures and records the pattern of shadows created by the sample.

The device processes these patterns as a series of holograms, forming 3-D images of the specimen and giving medical personnel a virtual depth-of-field view. An algorithm color codes the reconstructed images, making the contrasts in the samples more apparent than they would be in the holograms and making any abnormalities easier to detect.

Dr Ozcan’s team tested the device using blood samples containing sickle cell anemia, Pap smears that indicated cervical cancer, and tissue specimens containing cancerous breast cells.

In a blind test, a board-certified pathologist analyzed sets of specimen images that had been created by the lens-free technology and by conventional microscopes. The pathologist’s diagnoses using the lens-free microscopic images proved accurate 99% of the time.

Another benefit of the lens-free device, according to the researchers, is that it produces images that are several hundred times larger in area, or field of view, than those captured by conventional bright-field optical microscopes. This makes it possible to process specimens more quickly.

“While mobile healthcare has expanded rapidly with the growth of consumer electronics—cellphones in particular—pathology is still, by and large, constrained to advanced clinical laboratory settings,” Dr Ozcan said. “Accompanied by advances in its graphical user interface, this platform could scale up for use in clinical, biomedical, scientific, educational, and citizen-science applications, among others.”