Hematology Times

Sedimented red blood cells

An experimental drug designed to help regulate the blood’s iron supply may be a viable treatment option for inflammation-induced anemia, according to a study published in Blood.

The only current treatment strategy for this type of anemia involves targeting the underlying disease or infection.

However, recent research has sought to explore additional options for patients whose inflammation is difficult to control or when the cause of inflammation is unknown.

A hepcidin inhibitor called lexaptepid pegol (lexaptepid) has demonstrated efficacy in treating inflammation-induced anemia in animal studies. Lexaptepid inactivates hepcidin, thereby maintaining the transport of iron to the bloodstream.

To evaluate lexaptepid’s potential in humans, investigators caused inflammation-induced anemia in 24 healthy male adults and randomized them to receive lexaptepid or placebo.

Subjects received a low dose of Escherichia coli endotoxin to induce controlled inflammation and received either lexaptepid or placebo 30 minutes later.

After 9 hours, serum iron had decreased by 8.3±9.0 μmol/L in controls but increased by 15.9±9.8 μmol/L in lexaptepid-treated subjects (P<0.0001).

In addition to evaluating whether lexaptepid interfered with hepcidin production, the researchers also sought to determine whether the drug influenced the immune response.

Results suggested it did not. Treated subjects and controls alike experienced flu-like symptoms, increased body temperature and white blood cell counts, and higher concentrations of inflammatory and signaling proteins.

“It is quite encouraging that lexaptepid helped maintain appropriate levels of iron in the bloodstream of healthy volunteers without compromising the immune response,” said lead study author Lucas van Eijk, MD, of Radboud University Medical Center in Nijmegen, The Netherlands.

“We are hopeful that, with further study, this first-of-its-kind therapy could significantly improve quality of life for patients suffering from chronic illnesses.”

Results of a phase 2 study testing lexaptepid in anemic cancer patients were presented at the AACR Annual Meeting 2014.

Sedimented red blood cells

An experimental drug designed to help regulate the blood’s iron supply may be a viable treatment option for inflammation-induced anemia, according to a study published in Blood.

The only current treatment strategy for this type of anemia involves targeting the underlying disease or infection.

However, recent research has sought to explore additional options for patients whose inflammation is difficult to control or when the cause of inflammation is unknown.

A hepcidin inhibitor called lexaptepid pegol (lexaptepid) has demonstrated efficacy in treating inflammation-induced anemia in animal studies. Lexaptepid inactivates hepcidin, thereby maintaining the transport of iron to the bloodstream.

To evaluate lexaptepid’s potential in humans, investigators caused inflammation-induced anemia in 24 healthy male adults and randomized them to receive lexaptepid or placebo.

Subjects received a low dose of Escherichia coli endotoxin to induce controlled inflammation and received either lexaptepid or placebo 30 minutes later.

After 9 hours, serum iron had decreased by 8.3±9.0 μmol/L in controls but increased by 15.9±9.8 μmol/L in lexaptepid-treated subjects (P<0.0001).

In addition to evaluating whether lexaptepid interfered with hepcidin production, the researchers also sought to determine whether the drug influenced the immune response.

Results suggested it did not. Treated subjects and controls alike experienced flu-like symptoms, increased body temperature and white blood cell counts, and higher concentrations of inflammatory and signaling proteins.

“It is quite encouraging that lexaptepid helped maintain appropriate levels of iron in the bloodstream of healthy volunteers without compromising the immune response,” said lead study author Lucas van Eijk, MD, of Radboud University Medical Center in Nijmegen, The Netherlands.

“We are hopeful that, with further study, this first-of-its-kind therapy could significantly improve quality of life for patients suffering from chronic illnesses.”

Results of a phase 2 study testing lexaptepid in anemic cancer patients were presented at the AACR Annual Meeting 2014.

Sedimented red blood cells

An experimental drug designed to help regulate the blood’s iron supply may be a viable treatment option for inflammation-induced anemia, according to a study published in Blood.

The only current treatment strategy for this type of anemia involves targeting the underlying disease or infection.

However, recent research has sought to explore additional options for patients whose inflammation is difficult to control or when the cause of inflammation is unknown.

A hepcidin inhibitor called lexaptepid pegol (lexaptepid) has demonstrated efficacy in treating inflammation-induced anemia in animal studies. Lexaptepid inactivates hepcidin, thereby maintaining the transport of iron to the bloodstream.

To evaluate lexaptepid’s potential in humans, investigators caused inflammation-induced anemia in 24 healthy male adults and randomized them to receive lexaptepid or placebo.

Subjects received a low dose of Escherichia coli endotoxin to induce controlled inflammation and received either lexaptepid or placebo 30 minutes later.

After 9 hours, serum iron had decreased by 8.3±9.0 μmol/L in controls but increased by 15.9±9.8 μmol/L in lexaptepid-treated subjects (P<0.0001).

In addition to evaluating whether lexaptepid interfered with hepcidin production, the researchers also sought to determine whether the drug influenced the immune response.

Results suggested it did not. Treated subjects and controls alike experienced flu-like symptoms, increased body temperature and white blood cell counts, and higher concentrations of inflammatory and signaling proteins.

“It is quite encouraging that lexaptepid helped maintain appropriate levels of iron in the bloodstream of healthy volunteers without compromising the immune response,” said lead study author Lucas van Eijk, MD, of Radboud University Medical Center in Nijmegen, The Netherlands.

“We are hopeful that, with further study, this first-of-its-kind therapy could significantly improve quality of life for patients suffering from chronic illnesses.”

Results of a phase 2 study testing lexaptepid in anemic cancer patients were presented at the AACR Annual Meeting 2014.

Ugandan children

Credit: Malayaka house

Children repeatedly infected with malaria have been known to become asymptomatic, and researchers have found evidence suggesting a subset of γδ T cells play a role in this phenomenon.

Studying young children in Uganda, the team discovered that repeated malaria infection was associated with the loss and dysfunction of Vδ2+ γδ T cells.

This appeared to facilitate immunological tolerance of the malaria parasite and, therefore, a reduction in clinical symptoms.

“These inflammatory immune cells are depleted in children with repeated malaria exposure, and those that remain behave differently than the same cell types in children who have not previously been infected,” said Prasanna Jagannathan, MD, of the University of California, San Francisco (UCSF).

He and his colleagues reported these findings in Science Translational Medicine.

The researchers collected data on malaria infections, disease symptoms, and immune responses in 78 children who were monitored from infancy as part of a research collaboration between UCSF and Makarere University in Kampala, Africa. The study was conducted in Tororo, Uganda.

At 1 year of age, all children showed clinical symptoms of malaria with each infection. At 4 years, fewer than 10% were symptom-free upon infection. But 1 year later, more than 20% were symptom-free when infected.

The researchers found that repeated malaria infection was associated with the loss and dysfunction of Vδ2+ γδ T cells. They observed a decrease in cell proliferation and in the production of inflammatory cytokines (IFN-γ and TNF-α) in response to malaria antigens.

Repeated malaria infection was also associated with the upregulation of immunoregulatory pathways—increased expression of genes such as HAVCR2, FCRL6, LYN, BATF, and B3GAT1—that dampen the immune response.

Children with these characteristics were less likely than their peers to exhibit clinical symptoms upon subsequent malaria infection.

So it seems the depletion of Vδ2+ γδ T cells is beneficial in some ways and detrimental in others, said Margaret Feeney, MD, of UCSF. Individuals may no longer suffer symptoms, but they might not clear the parasite and could remain infectious.

Although this discovery has not provided a disease-fighting strategy as of yet, it does point to further avenues of study, according to Dr Feeney.

“We want to understand whether this is a generalizable phenomenon that also occurs among those who are first exposed to malaria as adults and in regions where malaria incidence is lower,” she said.

Dr Feeney speculates that malaria infection, by reshaping immune responses, might influence a person’s susceptibility to, and protection from, other infectious diseases.

Ugandan children

Credit: Malayaka house

Children repeatedly infected with malaria have been known to become asymptomatic, and researchers have found evidence suggesting a subset of γδ T cells play a role in this phenomenon.

Studying young children in Uganda, the team discovered that repeated malaria infection was associated with the loss and dysfunction of Vδ2+ γδ T cells.

This appeared to facilitate immunological tolerance of the malaria parasite and, therefore, a reduction in clinical symptoms.

“These inflammatory immune cells are depleted in children with repeated malaria exposure, and those that remain behave differently than the same cell types in children who have not previously been infected,” said Prasanna Jagannathan, MD, of the University of California, San Francisco (UCSF).

He and his colleagues reported these findings in Science Translational Medicine.

The researchers collected data on malaria infections, disease symptoms, and immune responses in 78 children who were monitored from infancy as part of a research collaboration between UCSF and Makarere University in Kampala, Africa. The study was conducted in Tororo, Uganda.

At 1 year of age, all children showed clinical symptoms of malaria with each infection. At 4 years, fewer than 10% were symptom-free upon infection. But 1 year later, more than 20% were symptom-free when infected.

The researchers found that repeated malaria infection was associated with the loss and dysfunction of Vδ2+ γδ T cells. They observed a decrease in cell proliferation and in the production of inflammatory cytokines (IFN-γ and TNF-α) in response to malaria antigens.

Repeated malaria infection was also associated with the upregulation of immunoregulatory pathways—increased expression of genes such as HAVCR2, FCRL6, LYN, BATF, and B3GAT1—that dampen the immune response.

Children with these characteristics were less likely than their peers to exhibit clinical symptoms upon subsequent malaria infection.

So it seems the depletion of Vδ2+ γδ T cells is beneficial in some ways and detrimental in others, said Margaret Feeney, MD, of UCSF. Individuals may no longer suffer symptoms, but they might not clear the parasite and could remain infectious.

Although this discovery has not provided a disease-fighting strategy as of yet, it does point to further avenues of study, according to Dr Feeney.

“We want to understand whether this is a generalizable phenomenon that also occurs among those who are first exposed to malaria as adults and in regions where malaria incidence is lower,” she said.

Dr Feeney speculates that malaria infection, by reshaping immune responses, might influence a person’s susceptibility to, and protection from, other infectious diseases.

Ugandan children

Credit: Malayaka house

Children repeatedly infected with malaria have been known to become asymptomatic, and researchers have found evidence suggesting a subset of γδ T cells play a role in this phenomenon.

Studying young children in Uganda, the team discovered that repeated malaria infection was associated with the loss and dysfunction of Vδ2+ γδ T cells.

This appeared to facilitate immunological tolerance of the malaria parasite and, therefore, a reduction in clinical symptoms.

“These inflammatory immune cells are depleted in children with repeated malaria exposure, and those that remain behave differently than the same cell types in children who have not previously been infected,” said Prasanna Jagannathan, MD, of the University of California, San Francisco (UCSF).

He and his colleagues reported these findings in Science Translational Medicine.

The researchers collected data on malaria infections, disease symptoms, and immune responses in 78 children who were monitored from infancy as part of a research collaboration between UCSF and Makarere University in Kampala, Africa. The study was conducted in Tororo, Uganda.

At 1 year of age, all children showed clinical symptoms of malaria with each infection. At 4 years, fewer than 10% were symptom-free upon infection. But 1 year later, more than 20% were symptom-free when infected.

The researchers found that repeated malaria infection was associated with the loss and dysfunction of Vδ2+ γδ T cells. They observed a decrease in cell proliferation and in the production of inflammatory cytokines (IFN-γ and TNF-α) in response to malaria antigens.

Repeated malaria infection was also associated with the upregulation of immunoregulatory pathways—increased expression of genes such as HAVCR2, FCRL6, LYN, BATF, and B3GAT1—that dampen the immune response.

Children with these characteristics were less likely than their peers to exhibit clinical symptoms upon subsequent malaria infection.

So it seems the depletion of Vδ2+ γδ T cells is beneficial in some ways and detrimental in others, said Margaret Feeney, MD, of UCSF. Individuals may no longer suffer symptoms, but they might not clear the parasite and could remain infectious.

Although this discovery has not provided a disease-fighting strategy as of yet, it does point to further avenues of study, according to Dr Feeney.

“We want to understand whether this is a generalizable phenomenon that also occurs among those who are first exposed to malaria as adults and in regions where malaria incidence is lower,” she said.

Dr Feeney speculates that malaria infection, by reshaping immune responses, might influence a person’s susceptibility to, and protection from, other infectious diseases.

Drug release in a cancer cell

Credit: PNAS

A new type of nanoparticle (NP) could aid the diagnosis and treatment of cancers, according to research published in Nature Communications.

Built on an easy-to-make polymer, these particles can be used as contrast agents to light up tumors for MRI and PET scans or to deliver chemotherapy and other treatments to cancer cells.

Furthermore, in vivo experiments showed the particles are biocompatible and elicit minimal side effects.

“These are amazingly useful particles,” said study author Yuanpei Li, PhD, of the UC Davis Comprehensive Cancer Center in Sacramento, California.

“As a contrast agent, they make tumors easier to see on MRI and other scans. We can also use them as vehicles to deliver chemotherapy directly to tumors, apply light to make the nanoparticles release singlet oxygen (photodynamic therapy), or use a laser to heat them (photothermal therapy)—all proven ways to destroy tumors.”

These NPs are built on a porphyrin/cholic acid polymer. Porphyrins are common organic compounds, and cholic acid is produced by the liver.

To further stabilize the particles, the researchers added the amino acid cysteine (creating CNPs), which prevents them from prematurely releasing their therapeutic payload when exposed to blood proteins and other barriers.

Therapeutic applications

The researchers tested the CNPs, both in vitro and in vivo, for a wide range of tasks. On the therapeutic side, the particles effectively transported anticancer drugs, such as doxorubicin.

CNPs carrying doxorubicin provided excellent cancer control in animals, with minimal side effects.

Even when kept in the blood for many hours, CNPs only released small amounts of the drug. However, when exposed to light or agents such as glutathione, they readily released their payloads.

The researchers showed that, when exposed to a single wavelength of light, the CNPs could generate heat or produce singlet oxygen to destroy tumor cells.

Imaging applications

CNPs offer a number of advantages to enhance imaging, according to the researchers. The particles readily chelate imaging agents and can remain in the body for long periods.

In animal studies, CNPs largely accumulated in tumors, rather than in normal tissue. So they dramatically enhanced tumor contrast for MRI and may also be promising for PET-MRI scans, the researchers said.

“These particles can combine imaging and therapeutics,” Dr Li noted. “We could potentially use them to simultaneously deliver treatment and monitor treatment efficacy.”

The researchers are now conducting additional preclinical studies with the CNPs. If all goes well, they will proceed to human trials. In the meantime, the team is excited about these capabilities.

“This is the first nanoparticle to perform so many different jobs,” Dr Li said. “From delivering chemo, photodynamic, and photothermal therapies, to enhancing diagnostic imaging, it’s the complete package.”

Drug release in a cancer cell

Credit: PNAS

A new type of nanoparticle (NP) could aid the diagnosis and treatment of cancers, according to research published in Nature Communications.

Built on an easy-to-make polymer, these particles can be used as contrast agents to light up tumors for MRI and PET scans or to deliver chemotherapy and other treatments to cancer cells.

Furthermore, in vivo experiments showed the particles are biocompatible and elicit minimal side effects.

“These are amazingly useful particles,” said study author Yuanpei Li, PhD, of the UC Davis Comprehensive Cancer Center in Sacramento, California.

“As a contrast agent, they make tumors easier to see on MRI and other scans. We can also use them as vehicles to deliver chemotherapy directly to tumors, apply light to make the nanoparticles release singlet oxygen (photodynamic therapy), or use a laser to heat them (photothermal therapy)—all proven ways to destroy tumors.”

These NPs are built on a porphyrin/cholic acid polymer. Porphyrins are common organic compounds, and cholic acid is produced by the liver.

To further stabilize the particles, the researchers added the amino acid cysteine (creating CNPs), which prevents them from prematurely releasing their therapeutic payload when exposed to blood proteins and other barriers.

Therapeutic applications

The researchers tested the CNPs, both in vitro and in vivo, for a wide range of tasks. On the therapeutic side, the particles effectively transported anticancer drugs, such as doxorubicin.

CNPs carrying doxorubicin provided excellent cancer control in animals, with minimal side effects.

Even when kept in the blood for many hours, CNPs only released small amounts of the drug. However, when exposed to light or agents such as glutathione, they readily released their payloads.

The researchers showed that, when exposed to a single wavelength of light, the CNPs could generate heat or produce singlet oxygen to destroy tumor cells.

Imaging applications

CNPs offer a number of advantages to enhance imaging, according to the researchers. The particles readily chelate imaging agents and can remain in the body for long periods.

In animal studies, CNPs largely accumulated in tumors, rather than in normal tissue. So they dramatically enhanced tumor contrast for MRI and may also be promising for PET-MRI scans, the researchers said.

“These particles can combine imaging and therapeutics,” Dr Li noted. “We could potentially use them to simultaneously deliver treatment and monitor treatment efficacy.”

The researchers are now conducting additional preclinical studies with the CNPs. If all goes well, they will proceed to human trials. In the meantime, the team is excited about these capabilities.

“This is the first nanoparticle to perform so many different jobs,” Dr Li said. “From delivering chemo, photodynamic, and photothermal therapies, to enhancing diagnostic imaging, it’s the complete package.”

Drug release in a cancer cell

Credit: PNAS

A new type of nanoparticle (NP) could aid the diagnosis and treatment of cancers, according to research published in Nature Communications.

Built on an easy-to-make polymer, these particles can be used as contrast agents to light up tumors for MRI and PET scans or to deliver chemotherapy and other treatments to cancer cells.

Furthermore, in vivo experiments showed the particles are biocompatible and elicit minimal side effects.

“These are amazingly useful particles,” said study author Yuanpei Li, PhD, of the UC Davis Comprehensive Cancer Center in Sacramento, California.

“As a contrast agent, they make tumors easier to see on MRI and other scans. We can also use them as vehicles to deliver chemotherapy directly to tumors, apply light to make the nanoparticles release singlet oxygen (photodynamic therapy), or use a laser to heat them (photothermal therapy)—all proven ways to destroy tumors.”

These NPs are built on a porphyrin/cholic acid polymer. Porphyrins are common organic compounds, and cholic acid is produced by the liver.

To further stabilize the particles, the researchers added the amino acid cysteine (creating CNPs), which prevents them from prematurely releasing their therapeutic payload when exposed to blood proteins and other barriers.

Therapeutic applications

The researchers tested the CNPs, both in vitro and in vivo, for a wide range of tasks. On the therapeutic side, the particles effectively transported anticancer drugs, such as doxorubicin.

CNPs carrying doxorubicin provided excellent cancer control in animals, with minimal side effects.

Even when kept in the blood for many hours, CNPs only released small amounts of the drug. However, when exposed to light or agents such as glutathione, they readily released their payloads.

The researchers showed that, when exposed to a single wavelength of light, the CNPs could generate heat or produce singlet oxygen to destroy tumor cells.

Imaging applications

CNPs offer a number of advantages to enhance imaging, according to the researchers. The particles readily chelate imaging agents and can remain in the body for long periods.

In animal studies, CNPs largely accumulated in tumors, rather than in normal tissue. So they dramatically enhanced tumor contrast for MRI and may also be promising for PET-MRI scans, the researchers said.

“These particles can combine imaging and therapeutics,” Dr Li noted. “We could potentially use them to simultaneously deliver treatment and monitor treatment efficacy.”

The researchers are now conducting additional preclinical studies with the CNPs. If all goes well, they will proceed to human trials. In the meantime, the team is excited about these capabilities.

“This is the first nanoparticle to perform so many different jobs,” Dr Li said. “From delivering chemo, photodynamic, and photothermal therapies, to enhancing diagnostic imaging, it’s the complete package.”

Lab mouse

Investigators at the Japanese research institute RIKEN have failed to create STAP (stimulus-triggered acquisition of pluripotency) cells in the experiments they’ve conducted thus far.

However, the group plans to continue its attempts to replicate the STAP cell phenomenon—inducing pluripotency in somatic cells by exposing them to stress—until next March.

So far, the group has failed to create STAP cells by exposing cells from newborn C57BL/6 mice to a low-pH environment.

Going forward, the researchers plan to conduct their experiments in another mouse strain. They also intend to alter the methods of stressing the cells.

RIKEN investigator Haruko Obokata, PhD, and her colleagues initially reported the STAP cell phenomenon in an article and a letter published in Nature last January.

Not long after the papers were published, members of the scientific community began to question the validity of the research. They voiced concerns about published images, possible plagiarism, and an inability to replicate the experiments described.

So RIKEN launched an investigation, ultimately concluding that Dr Obokata was guilty of misconduct, and some of her colleagues—including the recently deceased Yoshiki Sasai, MD, PhD—were guilty of negligence.

RIKEN also called for the papers to be retracted, and, in July, they were.

Throughout these proceedings, Dr Obokata insisted the STAP cell phenomenon is real. To investigate this claim, RIKEN organized a group of researchers to recreate Dr Obokata’s experiments.

The group has performed 22 experiments using different types of stress and cells from different tissues in C57BL/6 mice, but they have not reproduced the STAP cell phenomenon described in the Nature papers. (A report on these attempts is available in Japanese.)

Still, the investigators are continuing with their experiments and hope to have definitive results by March.

Lab mouse

Investigators at the Japanese research institute RIKEN have failed to create STAP (stimulus-triggered acquisition of pluripotency) cells in the experiments they’ve conducted thus far.

However, the group plans to continue its attempts to replicate the STAP cell phenomenon—inducing pluripotency in somatic cells by exposing them to stress—until next March.

So far, the group has failed to create STAP cells by exposing cells from newborn C57BL/6 mice to a low-pH environment.

Going forward, the researchers plan to conduct their experiments in another mouse strain. They also intend to alter the methods of stressing the cells.

RIKEN investigator Haruko Obokata, PhD, and her colleagues initially reported the STAP cell phenomenon in an article and a letter published in Nature last January.

Not long after the papers were published, members of the scientific community began to question the validity of the research. They voiced concerns about published images, possible plagiarism, and an inability to replicate the experiments described.

So RIKEN launched an investigation, ultimately concluding that Dr Obokata was guilty of misconduct, and some of her colleagues—including the recently deceased Yoshiki Sasai, MD, PhD—were guilty of negligence.

RIKEN also called for the papers to be retracted, and, in July, they were.

Throughout these proceedings, Dr Obokata insisted the STAP cell phenomenon is real. To investigate this claim, RIKEN organized a group of researchers to recreate Dr Obokata’s experiments.

The group has performed 22 experiments using different types of stress and cells from different tissues in C57BL/6 mice, but they have not reproduced the STAP cell phenomenon described in the Nature papers. (A report on these attempts is available in Japanese.)

Still, the investigators are continuing with their experiments and hope to have definitive results by March.

Lab mouse

Investigators at the Japanese research institute RIKEN have failed to create STAP (stimulus-triggered acquisition of pluripotency) cells in the experiments they’ve conducted thus far.

However, the group plans to continue its attempts to replicate the STAP cell phenomenon—inducing pluripotency in somatic cells by exposing them to stress—until next March.

So far, the group has failed to create STAP cells by exposing cells from newborn C57BL/6 mice to a low-pH environment.

Going forward, the researchers plan to conduct their experiments in another mouse strain. They also intend to alter the methods of stressing the cells.

RIKEN investigator Haruko Obokata, PhD, and her colleagues initially reported the STAP cell phenomenon in an article and a letter published in Nature last January.

Not long after the papers were published, members of the scientific community began to question the validity of the research. They voiced concerns about published images, possible plagiarism, and an inability to replicate the experiments described.

So RIKEN launched an investigation, ultimately concluding that Dr Obokata was guilty of misconduct, and some of her colleagues—including the recently deceased Yoshiki Sasai, MD, PhD—were guilty of negligence.

RIKEN also called for the papers to be retracted, and, in July, they were.

Throughout these proceedings, Dr Obokata insisted the STAP cell phenomenon is real. To investigate this claim, RIKEN organized a group of researchers to recreate Dr Obokata’s experiments.

The group has performed 22 experiments using different types of stress and cells from different tissues in C57BL/6 mice, but they have not reproduced the STAP cell phenomenon described in the Nature papers. (A report on these attempts is available in Japanese.)

Still, the investigators are continuing with their experiments and hope to have definitive results by March.

Doctor examining a child

Credit: Logan Tuttle

Weekend hospitalization can have its pitfalls, according to a study of pediatric patients newly diagnosed with leukemia.

Patients who were admitted to the hospital over the weekend had a longer length of stay, a slightly longer wait to start chemotherapy, and a higher risk for respiratory failure than patients admitted during the week.

Elizabeth K. Goodman, of the Children’s Hospital of Philadelphia, and her colleagues reported these results in JAMA Pediatrics.

The team examined adverse clinical outcomes associated with a weekend admission for the first hospitalization of pediatric patients newly diagnosed with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML).

The researchers used data from the Pediatric Health Information System database, which included patients admitted to 43 children’s hospitals from 1999 through 2011.

There were 10,720 patients with ALL and 1323 with AML. Roughly 17% of these patients (n=2009) were admitted to the hospital on the weekend.

Patients hospitalized on the weekend were similar to those hospitalized during the week with regard to disease type and sex. However, weekend admissions had significantly higher percentages of patients who were younger than 5 years of age, of nonwhite race/ethnicity, and publicly insured.

Patients admitted on the weekend were also more likely to be severely ill. They were significantly more likely to require ICU-level care within the first 2 days of admission (4.8% vs 3.1%, P<0.001).

An unadjusted analysis showed that inpatient mortality was similar for patients admitted to the hospital during the week and on the weekend (0.8% and 1.0%, respectively).

However, patients admitted on the weekend had a significantly longer mean hospital stay (17.8 vs 15.8 days, P<0.001) and a longer mean wait time for chemotherapy (3.9 vs 3.5 days, P<0.001).

Patients admitted on the weekend also had an increased risk of cardiovascular failure (6.4% vs 5.0%, P=0.01), respiratory failure (8.5% vs 5.7%, P<0.001), and andrenal failure (10.2% vs 8.3%, P=0.01).

However, some of these results changed when the researchers adjusted for demographic variables (disease, sex, age, race/ethnicity, and insurance), the presence of severe illness at admission, and hospital-level factors (presence of a fellowship program, Magnet status, percentage of public payers per admissions per hospital per year, and number of oncology admissions per hospital per year).

In the adjusted analysis, weekend admission remained associated with an increase in the length of hospital stay (1.4 days) and an increase in the time to chemotherapy (0.4 days).

Weekend admission also remained associated with an increased risk of respiratory failure (odds ratio, 1.5), but it was no longer associated with an increased risk of cardiovascular or renal failure.

The researchers said these findings highlight a potential area for improvement in patient care and cost reduction. Increasing weekend resources could help reduce patients’ length of stay and ensure they receive comprehensive care.

On the other hand, it might also raise hospital expenditures without decreasing negative outcomes. So additional research is needed to determine the most clinically and cost-effective combination of hospital resources to reduce the length of stay and improve outcomes for pediatric leukemia patients.

An editorial related to this study is available in JAMA Pediatrics.

Doctor examining a child

Credit: Logan Tuttle

Weekend hospitalization can have its pitfalls, according to a study of pediatric patients newly diagnosed with leukemia.

Patients who were admitted to the hospital over the weekend had a longer length of stay, a slightly longer wait to start chemotherapy, and a higher risk for respiratory failure than patients admitted during the week.

Elizabeth K. Goodman, of the Children’s Hospital of Philadelphia, and her colleagues reported these results in JAMA Pediatrics.

The team examined adverse clinical outcomes associated with a weekend admission for the first hospitalization of pediatric patients newly diagnosed with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML).

The researchers used data from the Pediatric Health Information System database, which included patients admitted to 43 children’s hospitals from 1999 through 2011.

There were 10,720 patients with ALL and 1323 with AML. Roughly 17% of these patients (n=2009) were admitted to the hospital on the weekend.

Patients hospitalized on the weekend were similar to those hospitalized during the week with regard to disease type and sex. However, weekend admissions had significantly higher percentages of patients who were younger than 5 years of age, of nonwhite race/ethnicity, and publicly insured.

Patients admitted on the weekend were also more likely to be severely ill. They were significantly more likely to require ICU-level care within the first 2 days of admission (4.8% vs 3.1%, P<0.001).

An unadjusted analysis showed that inpatient mortality was similar for patients admitted to the hospital during the week and on the weekend (0.8% and 1.0%, respectively).

However, patients admitted on the weekend had a significantly longer mean hospital stay (17.8 vs 15.8 days, P<0.001) and a longer mean wait time for chemotherapy (3.9 vs 3.5 days, P<0.001).

Patients admitted on the weekend also had an increased risk of cardiovascular failure (6.4% vs 5.0%, P=0.01), respiratory failure (8.5% vs 5.7%, P<0.001), and andrenal failure (10.2% vs 8.3%, P=0.01).

However, some of these results changed when the researchers adjusted for demographic variables (disease, sex, age, race/ethnicity, and insurance), the presence of severe illness at admission, and hospital-level factors (presence of a fellowship program, Magnet status, percentage of public payers per admissions per hospital per year, and number of oncology admissions per hospital per year).

In the adjusted analysis, weekend admission remained associated with an increase in the length of hospital stay (1.4 days) and an increase in the time to chemotherapy (0.4 days).

Weekend admission also remained associated with an increased risk of respiratory failure (odds ratio, 1.5), but it was no longer associated with an increased risk of cardiovascular or renal failure.

The researchers said these findings highlight a potential area for improvement in patient care and cost reduction. Increasing weekend resources could help reduce patients’ length of stay and ensure they receive comprehensive care.

On the other hand, it might also raise hospital expenditures without decreasing negative outcomes. So additional research is needed to determine the most clinically and cost-effective combination of hospital resources to reduce the length of stay and improve outcomes for pediatric leukemia patients.

An editorial related to this study is available in JAMA Pediatrics.

Doctor examining a child

Credit: Logan Tuttle

Weekend hospitalization can have its pitfalls, according to a study of pediatric patients newly diagnosed with leukemia.

Patients who were admitted to the hospital over the weekend had a longer length of stay, a slightly longer wait to start chemotherapy, and a higher risk for respiratory failure than patients admitted during the week.

Elizabeth K. Goodman, of the Children’s Hospital of Philadelphia, and her colleagues reported these results in JAMA Pediatrics.

The team examined adverse clinical outcomes associated with a weekend admission for the first hospitalization of pediatric patients newly diagnosed with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML).

The researchers used data from the Pediatric Health Information System database, which included patients admitted to 43 children’s hospitals from 1999 through 2011.

There were 10,720 patients with ALL and 1323 with AML. Roughly 17% of these patients (n=2009) were admitted to the hospital on the weekend.

Patients hospitalized on the weekend were similar to those hospitalized during the week with regard to disease type and sex. However, weekend admissions had significantly higher percentages of patients who were younger than 5 years of age, of nonwhite race/ethnicity, and publicly insured.

Patients admitted on the weekend were also more likely to be severely ill. They were significantly more likely to require ICU-level care within the first 2 days of admission (4.8% vs 3.1%, P<0.001).

An unadjusted analysis showed that inpatient mortality was similar for patients admitted to the hospital during the week and on the weekend (0.8% and 1.0%, respectively).

However, patients admitted on the weekend had a significantly longer mean hospital stay (17.8 vs 15.8 days, P<0.001) and a longer mean wait time for chemotherapy (3.9 vs 3.5 days, P<0.001).

Patients admitted on the weekend also had an increased risk of cardiovascular failure (6.4% vs 5.0%, P=0.01), respiratory failure (8.5% vs 5.7%, P<0.001), and andrenal failure (10.2% vs 8.3%, P=0.01).

However, some of these results changed when the researchers adjusted for demographic variables (disease, sex, age, race/ethnicity, and insurance), the presence of severe illness at admission, and hospital-level factors (presence of a fellowship program, Magnet status, percentage of public payers per admissions per hospital per year, and number of oncology admissions per hospital per year).

In the adjusted analysis, weekend admission remained associated with an increase in the length of hospital stay (1.4 days) and an increase in the time to chemotherapy (0.4 days).

Weekend admission also remained associated with an increased risk of respiratory failure (odds ratio, 1.5), but it was no longer associated with an increased risk of cardiovascular or renal failure.

The researchers said these findings highlight a potential area for improvement in patient care and cost reduction. Increasing weekend resources could help reduce patients’ length of stay and ensure they receive comprehensive care.

On the other hand, it might also raise hospital expenditures without decreasing negative outcomes. So additional research is needed to determine the most clinically and cost-effective combination of hospital resources to reduce the length of stay and improve outcomes for pediatric leukemia patients.

An editorial related to this study is available in JAMA Pediatrics.

The US Food and Drug Administration (FDA) has approved eltrombopag (Promacta) for use in patients with severe aplastic anemia (SAA) who have had an insufficient response to immunosuppressive therapy (IST).

Eltrombopag is an oral thrombopoietin receptor agonist that helps to induce the proliferation and differentiation of hematopoietic stem cells to increase blood cell production.

Eltrombopag is already FDA approved to treat patients with chronic immune thrombocytopenia who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.

The drug is also approved to treat thrombocytopenia in patients with chronic hepatitis C to allow for the initiation and maintenance of interferon-based therapy.

The latest FDA approval is based on results from an investigator-sponsored phase 2 study (09-H-0154) conducted by the National Heart, Lung and Blood Institute. Results of this trial were previously published in The New England Journal of Medicine.

Eltrombopag in SAA: Latest trial results

In this study, researchers evaluated eltrombopag in 43 SAA patients who had an insufficient response to at least 1 prior IST and a platelet count of 30 x 10⁹/L or less.

At baseline, the median platelet count was 20 x 10⁹/L, hemoglobin was 8.4 g/dL, the absolute neutrophil count was 0.58 x 10⁹/L, and absolute reticulocyte count was 24.3 x 10⁹/L.

Patients had a median age of 45 years (range, 17 to 77 years), and 56% were male. The majority of patients (84%) received at least 2 prior ISTs.

Patients received eltrombopag at an initial dose of 50 mg once daily for 2 weeks. The dose increased over 2-week periods to a maximum of 150 mg once daily.

The study’s primary endpoint was hematologic response, which was initially assessed after 12 weeks of treatment. Treatment was discontinued after 16 weeks in patients who did not exhibit a hematologic response.

Forty percent of patients (N=17) experienced a hematologic response in at least one lineage—platelets, red blood cells (RBCs), or white blood cells—after week 12.

In the extension phase of the study, 8 patients achieved a multilineage response. Four of these patients subsequently tapered off treatment and maintained the response. The median follow up was 8.1 months (range, 7.2 to 10.6 months).

Ninety-one percent of patients were platelet-transfusion-dependent at baseline. Patients who responded to eltrombopag did not require platelet transfusions for a median of 200 days (range, 8 to 1096 days).

Eighty-six percent of patients were RBC-transfusion-dependent at baseline. Patients who responded to eltrombopag did not require RBC transfusions for a median of 208 days (range, 15 to 1082 days).

The most common adverse events (≥20%) associated with eltrombopag were nausea (33%), fatigue (28%), cough (23%), diarrhea (21%), and headache (21%).

Patients also had bone marrow aspirates evaluated for cytogenetic abnormalities. Eight patients had a new cytogenetic abnormality after treatment, including 5 patients who had complex changes in chromosome 7.

Patients who develop new cytogenetic abnormalities while on eltrombopag may need to be taken off treatment.

Eltrombopag is marketed by GlaxoSmithKline under the brand name Promacta in the US and Revolade in most other countries. For more information on eltrombopag, see the prescribing information.

The US Food and Drug Administration (FDA) has approved eltrombopag (Promacta) for use in patients with severe aplastic anemia (SAA) who have had an insufficient response to immunosuppressive therapy (IST).

Eltrombopag is an oral thrombopoietin receptor agonist that helps to induce the proliferation and differentiation of hematopoietic stem cells to increase blood cell production.

Eltrombopag is already FDA approved to treat patients with chronic immune thrombocytopenia who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.

The drug is also approved to treat thrombocytopenia in patients with chronic hepatitis C to allow for the initiation and maintenance of interferon-based therapy.

The latest FDA approval is based on results from an investigator-sponsored phase 2 study (09-H-0154) conducted by the National Heart, Lung and Blood Institute. Results of this trial were previously published in The New England Journal of Medicine.

Eltrombopag in SAA: Latest trial results

In this study, researchers evaluated eltrombopag in 43 SAA patients who had an insufficient response to at least 1 prior IST and a platelet count of 30 x 10⁹/L or less.

At baseline, the median platelet count was 20 x 10⁹/L, hemoglobin was 8.4 g/dL, the absolute neutrophil count was 0.58 x 10⁹/L, and absolute reticulocyte count was 24.3 x 10⁹/L.

Patients had a median age of 45 years (range, 17 to 77 years), and 56% were male. The majority of patients (84%) received at least 2 prior ISTs.

Patients received eltrombopag at an initial dose of 50 mg once daily for 2 weeks. The dose increased over 2-week periods to a maximum of 150 mg once daily.

The study’s primary endpoint was hematologic response, which was initially assessed after 12 weeks of treatment. Treatment was discontinued after 16 weeks in patients who did not exhibit a hematologic response.

Forty percent of patients (N=17) experienced a hematologic response in at least one lineage—platelets, red blood cells (RBCs), or white blood cells—after week 12.

In the extension phase of the study, 8 patients achieved a multilineage response. Four of these patients subsequently tapered off treatment and maintained the response. The median follow up was 8.1 months (range, 7.2 to 10.6 months).

Ninety-one percent of patients were platelet-transfusion-dependent at baseline. Patients who responded to eltrombopag did not require platelet transfusions for a median of 200 days (range, 8 to 1096 days).

Eighty-six percent of patients were RBC-transfusion-dependent at baseline. Patients who responded to eltrombopag did not require RBC transfusions for a median of 208 days (range, 15 to 1082 days).

The most common adverse events (≥20%) associated with eltrombopag were nausea (33%), fatigue (28%), cough (23%), diarrhea (21%), and headache (21%).

Patients also had bone marrow aspirates evaluated for cytogenetic abnormalities. Eight patients had a new cytogenetic abnormality after treatment, including 5 patients who had complex changes in chromosome 7.

Patients who develop new cytogenetic abnormalities while on eltrombopag may need to be taken off treatment.

Eltrombopag is marketed by GlaxoSmithKline under the brand name Promacta in the US and Revolade in most other countries. For more information on eltrombopag, see the prescribing information.

The US Food and Drug Administration (FDA) has approved eltrombopag (Promacta) for use in patients with severe aplastic anemia (SAA) who have had an insufficient response to immunosuppressive therapy (IST).

Eltrombopag is an oral thrombopoietin receptor agonist that helps to induce the proliferation and differentiation of hematopoietic stem cells to increase blood cell production.

Eltrombopag is already FDA approved to treat patients with chronic immune thrombocytopenia who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.

The drug is also approved to treat thrombocytopenia in patients with chronic hepatitis C to allow for the initiation and maintenance of interferon-based therapy.

The latest FDA approval is based on results from an investigator-sponsored phase 2 study (09-H-0154) conducted by the National Heart, Lung and Blood Institute. Results of this trial were previously published in The New England Journal of Medicine.

Eltrombopag in SAA: Latest trial results

In this study, researchers evaluated eltrombopag in 43 SAA patients who had an insufficient response to at least 1 prior IST and a platelet count of 30 x 10⁹/L or less.

At baseline, the median platelet count was 20 x 10⁹/L, hemoglobin was 8.4 g/dL, the absolute neutrophil count was 0.58 x 10⁹/L, and absolute reticulocyte count was 24.3 x 10⁹/L.

Patients had a median age of 45 years (range, 17 to 77 years), and 56% were male. The majority of patients (84%) received at least 2 prior ISTs.

Patients received eltrombopag at an initial dose of 50 mg once daily for 2 weeks. The dose increased over 2-week periods to a maximum of 150 mg once daily.

The study’s primary endpoint was hematologic response, which was initially assessed after 12 weeks of treatment. Treatment was discontinued after 16 weeks in patients who did not exhibit a hematologic response.

Forty percent of patients (N=17) experienced a hematologic response in at least one lineage—platelets, red blood cells (RBCs), or white blood cells—after week 12.

In the extension phase of the study, 8 patients achieved a multilineage response. Four of these patients subsequently tapered off treatment and maintained the response. The median follow up was 8.1 months (range, 7.2 to 10.6 months).

Ninety-one percent of patients were platelet-transfusion-dependent at baseline. Patients who responded to eltrombopag did not require platelet transfusions for a median of 200 days (range, 8 to 1096 days).

Eighty-six percent of patients were RBC-transfusion-dependent at baseline. Patients who responded to eltrombopag did not require RBC transfusions for a median of 208 days (range, 15 to 1082 days).

The most common adverse events (≥20%) associated with eltrombopag were nausea (33%), fatigue (28%), cough (23%), diarrhea (21%), and headache (21%).

Patients also had bone marrow aspirates evaluated for cytogenetic abnormalities. Eight patients had a new cytogenetic abnormality after treatment, including 5 patients who had complex changes in chromosome 7.

Patients who develop new cytogenetic abnormalities while on eltrombopag may need to be taken off treatment.

Eltrombopag is marketed by GlaxoSmithKline under the brand name Promacta in the US and Revolade in most other countries. For more information on eltrombopag, see the prescribing information.

Sleeping infant

Credit: Bertrand Devouard

Erythropoietin (EPO) can reduce the risk of brain injury in preterm infants, a new study suggests.

Infants who received 3 doses of EPO within 42 hours of birth were less likely than their untreated peers to have abnormal scores for white matter injury, white matter signal intensity, periventricular white matter loss, and gray matter injury.

Russia Ha-Vinh Leuchter, MD, of the University Hospital of Geneva in Switzerland, and her colleagues recounted these findings in JAMA.

The researchers evaluated 495 infants who were born in Switzerland between 2005 and 2012—at 26 weeks of gestation to 31 weeks and 6 days of gestation.

The children were randomized to receive EPO (n=256) or placebo (n=239) intravenously at 3 time points: before they reached 3 hours of age, at 12 to 18 hours after birth, and at 36 to 42 hours after birth.

Due to the limited availability of MRI, the researchers were only able to assess brain injury in a nonrandomized subset of 165 infants. Seventy-seven of these children received EPO, and 88 received placebo.

The patients underwent MRI at a median gestation age of 40 weeks and 5 days (range, 35 weeks and 5 days to 44 weeks and 6 days).

“We found that the brains of the children who had received the treatment had much less damage than those in the control group,” Dr Ha-Vinh Leuchter said. “This is the first time that the beneficial effect of the EPO hormone on the brains of premature babies has been shown.”

Specifically, the results showed that, at term-equivalent age, infants treated with EPO were less likely than controls to have abnormal scores for white matter injury (22% vs 36%), white matter signal intensity (3% vs 11%), periventricular white matter loss (18% vs 33%), and gray matter injury (7% vs 19%).

These results are only the first part of this study, according to the researchers. The second—and main—part of the work will focus on the neurocognitive development of these children, who will take part in various developmental tests at 2 and 5 years of age.

“[The tests] should confirm the effect that EPO treatment has on the neurodevelopmental disabilities that very premature babies often show during their infancy,” said Petra Hüppi, MD, also of the University Hospital of Geneva.

“If this does turn out to be the case, we will have taken an important step in preventing brain damage and its long-term consequences in premature babies.”

Sleeping infant

Credit: Bertrand Devouard

Erythropoietin (EPO) can reduce the risk of brain injury in preterm infants, a new study suggests.

Infants who received 3 doses of EPO within 42 hours of birth were less likely than their untreated peers to have abnormal scores for white matter injury, white matter signal intensity, periventricular white matter loss, and gray matter injury.

Russia Ha-Vinh Leuchter, MD, of the University Hospital of Geneva in Switzerland, and her colleagues recounted these findings in JAMA.

The researchers evaluated 495 infants who were born in Switzerland between 2005 and 2012—at 26 weeks of gestation to 31 weeks and 6 days of gestation.

The children were randomized to receive EPO (n=256) or placebo (n=239) intravenously at 3 time points: before they reached 3 hours of age, at 12 to 18 hours after birth, and at 36 to 42 hours after birth.

Due to the limited availability of MRI, the researchers were only able to assess brain injury in a nonrandomized subset of 165 infants. Seventy-seven of these children received EPO, and 88 received placebo.

The patients underwent MRI at a median gestation age of 40 weeks and 5 days (range, 35 weeks and 5 days to 44 weeks and 6 days).

“We found that the brains of the children who had received the treatment had much less damage than those in the control group,” Dr Ha-Vinh Leuchter said. “This is the first time that the beneficial effect of the EPO hormone on the brains of premature babies has been shown.”

Specifically, the results showed that, at term-equivalent age, infants treated with EPO were less likely than controls to have abnormal scores for white matter injury (22% vs 36%), white matter signal intensity (3% vs 11%), periventricular white matter loss (18% vs 33%), and gray matter injury (7% vs 19%).

These results are only the first part of this study, according to the researchers. The second—and main—part of the work will focus on the neurocognitive development of these children, who will take part in various developmental tests at 2 and 5 years of age.

“[The tests] should confirm the effect that EPO treatment has on the neurodevelopmental disabilities that very premature babies often show during their infancy,” said Petra Hüppi, MD, also of the University Hospital of Geneva.

“If this does turn out to be the case, we will have taken an important step in preventing brain damage and its long-term consequences in premature babies.”

Sleeping infant

Credit: Bertrand Devouard

Erythropoietin (EPO) can reduce the risk of brain injury in preterm infants, a new study suggests.

Infants who received 3 doses of EPO within 42 hours of birth were less likely than their untreated peers to have abnormal scores for white matter injury, white matter signal intensity, periventricular white matter loss, and gray matter injury.

Russia Ha-Vinh Leuchter, MD, of the University Hospital of Geneva in Switzerland, and her colleagues recounted these findings in JAMA.

The researchers evaluated 495 infants who were born in Switzerland between 2005 and 2012—at 26 weeks of gestation to 31 weeks and 6 days of gestation.

The children were randomized to receive EPO (n=256) or placebo (n=239) intravenously at 3 time points: before they reached 3 hours of age, at 12 to 18 hours after birth, and at 36 to 42 hours after birth.

Due to the limited availability of MRI, the researchers were only able to assess brain injury in a nonrandomized subset of 165 infants. Seventy-seven of these children received EPO, and 88 received placebo.

The patients underwent MRI at a median gestation age of 40 weeks and 5 days (range, 35 weeks and 5 days to 44 weeks and 6 days).

“We found that the brains of the children who had received the treatment had much less damage than those in the control group,” Dr Ha-Vinh Leuchter said. “This is the first time that the beneficial effect of the EPO hormone on the brains of premature babies has been shown.”

Specifically, the results showed that, at term-equivalent age, infants treated with EPO were less likely than controls to have abnormal scores for white matter injury (22% vs 36%), white matter signal intensity (3% vs 11%), periventricular white matter loss (18% vs 33%), and gray matter injury (7% vs 19%).

These results are only the first part of this study, according to the researchers. The second—and main—part of the work will focus on the neurocognitive development of these children, who will take part in various developmental tests at 2 and 5 years of age.

“[The tests] should confirm the effect that EPO treatment has on the neurodevelopmental disabilities that very premature babies often show during their infancy,” said Petra Hüppi, MD, also of the University Hospital of Geneva.

“If this does turn out to be the case, we will have taken an important step in preventing brain damage and its long-term consequences in premature babies.”

Thrombus

Credit: Andre E.X. Brown

Regado Biosciences, Inc., has permanently terminated enrollment in the phase 3 REGULATE-PCI trial due to serious allergic reactions in patients treated with the Revolixys Kit (also known as REG-1).

The kit is a 2-component system consisting of pegnivacogin, an anticoagulant aptamer specifically targeting coagulation factor IXa, and its complementary oligonucleotide active control agent, anivamersen.

The REGULATE-PCI trial is a comparison of the Revolixys Kit and bivilarudin in patients undergoing percutaneous coronary intervention.

A data and safety monitoring board analyzed data from the roughly 3250 patients initially enrolled in the trial and discovered serious allergic reactions in patients treated with Revolixys.

“The [board] indicated that the level of serious allergic adverse events associated with Revolixys was of a frequency and severity such that they recommended that we do not enroll any further patients in the REGULATE-PCI trial,” said David J. Mazzo, PhD, CEO of Regado.

“We will now undertake a complete review of the unblinded database from REGULATE-PCI, which we expect will take several months to complete.”

Dr Mazzo did not provide details as to the type of allergic reactions patients experienced or the incidence of these events. He did say the exact cause of the reactions is unknown, but the data review and investigation should reveal that information.

The review should also provide information that will help Regado decide how to move forward with its development of Revolixys (REG-1) and a related system known as REG-2.

For more information on REG-1 and REG-2, visit Regado’s website.  For more information on REGULATE-PCI, visit clinicaltrials.gov.

Thrombus

Credit: Andre E.X. Brown

Regado Biosciences, Inc., has permanently terminated enrollment in the phase 3 REGULATE-PCI trial due to serious allergic reactions in patients treated with the Revolixys Kit (also known as REG-1).

The kit is a 2-component system consisting of pegnivacogin, an anticoagulant aptamer specifically targeting coagulation factor IXa, and its complementary oligonucleotide active control agent, anivamersen.

The REGULATE-PCI trial is a comparison of the Revolixys Kit and bivilarudin in patients undergoing percutaneous coronary intervention.

A data and safety monitoring board analyzed data from the roughly 3250 patients initially enrolled in the trial and discovered serious allergic reactions in patients treated with Revolixys.

“The [board] indicated that the level of serious allergic adverse events associated with Revolixys was of a frequency and severity such that they recommended that we do not enroll any further patients in the REGULATE-PCI trial,” said David J. Mazzo, PhD, CEO of Regado.

“We will now undertake a complete review of the unblinded database from REGULATE-PCI, which we expect will take several months to complete.”

Dr Mazzo did not provide details as to the type of allergic reactions patients experienced or the incidence of these events. He did say the exact cause of the reactions is unknown, but the data review and investigation should reveal that information.

The review should also provide information that will help Regado decide how to move forward with its development of Revolixys (REG-1) and a related system known as REG-2.

For more information on REG-1 and REG-2, visit Regado’s website.  For more information on REGULATE-PCI, visit clinicaltrials.gov.

Thrombus

Credit: Andre E.X. Brown

Regado Biosciences, Inc., has permanently terminated enrollment in the phase 3 REGULATE-PCI trial due to serious allergic reactions in patients treated with the Revolixys Kit (also known as REG-1).

The kit is a 2-component system consisting of pegnivacogin, an anticoagulant aptamer specifically targeting coagulation factor IXa, and its complementary oligonucleotide active control agent, anivamersen.

The REGULATE-PCI trial is a comparison of the Revolixys Kit and bivilarudin in patients undergoing percutaneous coronary intervention.

A data and safety monitoring board analyzed data from the roughly 3250 patients initially enrolled in the trial and discovered serious allergic reactions in patients treated with Revolixys.

“The [board] indicated that the level of serious allergic adverse events associated with Revolixys was of a frequency and severity such that they recommended that we do not enroll any further patients in the REGULATE-PCI trial,” said David J. Mazzo, PhD, CEO of Regado.

“We will now undertake a complete review of the unblinded database from REGULATE-PCI, which we expect will take several months to complete.”

Dr Mazzo did not provide details as to the type of allergic reactions patients experienced or the incidence of these events. He did say the exact cause of the reactions is unknown, but the data review and investigation should reveal that information.

The review should also provide information that will help Regado decide how to move forward with its development of Revolixys (REG-1) and a related system known as REG-2.

For more information on REG-1 and REG-2, visit Regado’s website.  For more information on REGULATE-PCI, visit clinicaltrials.gov.

Aspirin tablets

Credit: Sage Ross

Low-dose aspirin can decrease the risk of major vascular events among patients with venous thromboembolism (VTE), according to a study published in Circulation.

The study included more than 1000 patients who had completed initial anticoagulant therapy after their first VTE.

Patients who went on to receive a daily dose of aspirin had a lower incidence of recurrent VTE, myocardial infarction, stroke, and cardiovascular death, compared

to those who received placebo.

The effects were not as substantial as those typically observed with warfarin or newer anticoagulants, but the results suggest low-dose aspirin is a feasible option for patients who cannot receive long-term anticoagulant therapy.

“The study provides evidence that, after a first venous thrombosis or embolism, daily aspirin reduces the risk of another event, without causing undue bleeding,” said study author John Simes, MD, of the University of Sydney in New South Wales, Australia.

“This treatment is an alternative to long-term anticoagulation and will be especially useful for patients who do not want the inconvenience of close medical monitoring or the risk of bleeding. [Additionally,] aspirin will be ideal in the many countries where prolonged anticoagulant treatment is too expensive.”

For this study, Dr Simes and his colleagues evaluated data from the ASPIRE and WARFASA trials. ASPIRE included 822 patients who were followed for an average of 3 years. And WARFASA included 402 patients who were followed for at least 2 years.

The patients had completed initial treatment with heparin and warfarin or an equivalent anticoagulant regimen following a first, unprovoked VTE. They were randomized to receive placebo (n=608) or a 100 mg daily dose of aspirin (n=616).

The researchers evaluated the differences between these 2 groups with regard to bleeding, recurrent VTE, and major vascular events, which includes recurrent VTE, myocardial infarction, stroke, and cardiovascular death.

VTE recurred in 18.4% of patients in the placebo arm and 13.1% of patients in the aspirin arm. The annual rate of recurrent VTE was 7.5% and 5.1%, respectively. So aspirin reduced the risk of VTE by 32% (hazard ratio [HR]=0.68, P=0.008).

Aspirin reduced the risk of deep vein thrombosis by 34% (HR=0.66, P=0.01) and the risk of pulmonary embolism by 34% (HR=0.66, P=0.08).

Aspirin also reduce the risk of major vascular events by 34%. The annual rate of these events was 5.7% in the aspirin arm and 8.7% in the placebo arm (HR=0.66, P=0.002).

There was no significant difference between the treatment arms with regard to bleeding. The annual rate of bleeding was 0.7% in the placebo arm and 1.1% in the aspirin arm. The annual rate of major bleeding was 0.4% and 0.5%, respectively.

“Aspirin does not require laboratory monitoring and is associated with about a 10-fold lower incidence of bleeding compared with oral anticoagulants,” said study author Cecilia Becattini, MD, of the University of Perugia in Italy.

“We are convinced that it will be an alternative for extended prevention of venous thromboembolism after 6 to 12 months of anticoagulant treatment.”

The researchers stressed that aspirin will not be a substitute for anticoagulant therapy in all patients. But it is an option for patients who are stopping anticoagulant therapy or for patients in whom long-term anticoagulant therapy is unsuitable.

“Although less effective, aspirin is inexpensive, easily obtainable, safe, and familiar to patients and clinicians worldwide,” Dr Simes noted. “If cost is the main consideration, aspirin is a particularly useful therapy. The costs of treating future thromboembolic events is greater than the cost of the preventive treatment.”

Aspirin tablets

Credit: Sage Ross

Low-dose aspirin can decrease the risk of major vascular events among patients with venous thromboembolism (VTE), according to a study published in Circulation.

The study included more than 1000 patients who had completed initial anticoagulant therapy after their first VTE.

Patients who went on to receive a daily dose of aspirin had a lower incidence of recurrent VTE, myocardial infarction, stroke, and cardiovascular death, compared

to those who received placebo.

The effects were not as substantial as those typically observed with warfarin or newer anticoagulants, but the results suggest low-dose aspirin is a feasible option for patients who cannot receive long-term anticoagulant therapy.

“The study provides evidence that, after a first venous thrombosis or embolism, daily aspirin reduces the risk of another event, without causing undue bleeding,” said study author John Simes, MD, of the University of Sydney in New South Wales, Australia.

“This treatment is an alternative to long-term anticoagulation and will be especially useful for patients who do not want the inconvenience of close medical monitoring or the risk of bleeding. [Additionally,] aspirin will be ideal in the many countries where prolonged anticoagulant treatment is too expensive.”

For this study, Dr Simes and his colleagues evaluated data from the ASPIRE and WARFASA trials. ASPIRE included 822 patients who were followed for an average of 3 years. And WARFASA included 402 patients who were followed for at least 2 years.

The patients had completed initial treatment with heparin and warfarin or an equivalent anticoagulant regimen following a first, unprovoked VTE. They were randomized to receive placebo (n=608) or a 100 mg daily dose of aspirin (n=616).

The researchers evaluated the differences between these 2 groups with regard to bleeding, recurrent VTE, and major vascular events, which includes recurrent VTE, myocardial infarction, stroke, and cardiovascular death.

VTE recurred in 18.4% of patients in the placebo arm and 13.1% of patients in the aspirin arm. The annual rate of recurrent VTE was 7.5% and 5.1%, respectively. So aspirin reduced the risk of VTE by 32% (hazard ratio [HR]=0.68, P=0.008).

Aspirin reduced the risk of deep vein thrombosis by 34% (HR=0.66, P=0.01) and the risk of pulmonary embolism by 34% (HR=0.66, P=0.08).

Aspirin also reduce the risk of major vascular events by 34%. The annual rate of these events was 5.7% in the aspirin arm and 8.7% in the placebo arm (HR=0.66, P=0.002).

There was no significant difference between the treatment arms with regard to bleeding. The annual rate of bleeding was 0.7% in the placebo arm and 1.1% in the aspirin arm. The annual rate of major bleeding was 0.4% and 0.5%, respectively.

“Aspirin does not require laboratory monitoring and is associated with about a 10-fold lower incidence of bleeding compared with oral anticoagulants,” said study author Cecilia Becattini, MD, of the University of Perugia in Italy.

“We are convinced that it will be an alternative for extended prevention of venous thromboembolism after 6 to 12 months of anticoagulant treatment.”

The researchers stressed that aspirin will not be a substitute for anticoagulant therapy in all patients. But it is an option for patients who are stopping anticoagulant therapy or for patients in whom long-term anticoagulant therapy is unsuitable.

“Although less effective, aspirin is inexpensive, easily obtainable, safe, and familiar to patients and clinicians worldwide,” Dr Simes noted. “If cost is the main consideration, aspirin is a particularly useful therapy. The costs of treating future thromboembolic events is greater than the cost of the preventive treatment.”

Aspirin tablets

Credit: Sage Ross

Low-dose aspirin can decrease the risk of major vascular events among patients with venous thromboembolism (VTE), according to a study published in Circulation.

The study included more than 1000 patients who had completed initial anticoagulant therapy after their first VTE.

Patients who went on to receive a daily dose of aspirin had a lower incidence of recurrent VTE, myocardial infarction, stroke, and cardiovascular death, compared

to those who received placebo.

The effects were not as substantial as those typically observed with warfarin or newer anticoagulants, but the results suggest low-dose aspirin is a feasible option for patients who cannot receive long-term anticoagulant therapy.

“The study provides evidence that, after a first venous thrombosis or embolism, daily aspirin reduces the risk of another event, without causing undue bleeding,” said study author John Simes, MD, of the University of Sydney in New South Wales, Australia.

“This treatment is an alternative to long-term anticoagulation and will be especially useful for patients who do not want the inconvenience of close medical monitoring or the risk of bleeding. [Additionally,] aspirin will be ideal in the many countries where prolonged anticoagulant treatment is too expensive.”

For this study, Dr Simes and his colleagues evaluated data from the ASPIRE and WARFASA trials. ASPIRE included 822 patients who were followed for an average of 3 years. And WARFASA included 402 patients who were followed for at least 2 years.

The patients had completed initial treatment with heparin and warfarin or an equivalent anticoagulant regimen following a first, unprovoked VTE. They were randomized to receive placebo (n=608) or a 100 mg daily dose of aspirin (n=616).

The researchers evaluated the differences between these 2 groups with regard to bleeding, recurrent VTE, and major vascular events, which includes recurrent VTE, myocardial infarction, stroke, and cardiovascular death.

VTE recurred in 18.4% of patients in the placebo arm and 13.1% of patients in the aspirin arm. The annual rate of recurrent VTE was 7.5% and 5.1%, respectively. So aspirin reduced the risk of VTE by 32% (hazard ratio [HR]=0.68, P=0.008).

Aspirin reduced the risk of deep vein thrombosis by 34% (HR=0.66, P=0.01) and the risk of pulmonary embolism by 34% (HR=0.66, P=0.08).

Aspirin also reduce the risk of major vascular events by 34%. The annual rate of these events was 5.7% in the aspirin arm and 8.7% in the placebo arm (HR=0.66, P=0.002).

There was no significant difference between the treatment arms with regard to bleeding. The annual rate of bleeding was 0.7% in the placebo arm and 1.1% in the aspirin arm. The annual rate of major bleeding was 0.4% and 0.5%, respectively.

“Aspirin does not require laboratory monitoring and is associated with about a 10-fold lower incidence of bleeding compared with oral anticoagulants,” said study author Cecilia Becattini, MD, of the University of Perugia in Italy.

“We are convinced that it will be an alternative for extended prevention of venous thromboembolism after 6 to 12 months of anticoagulant treatment.”

The researchers stressed that aspirin will not be a substitute for anticoagulant therapy in all patients. But it is an option for patients who are stopping anticoagulant therapy or for patients in whom long-term anticoagulant therapy is unsuitable.

“Although less effective, aspirin is inexpensive, easily obtainable, safe, and familiar to patients and clinicians worldwide,” Dr Simes noted. “If cost is the main consideration, aspirin is a particularly useful therapy. The costs of treating future thromboembolic events is greater than the cost of the preventive treatment.”

DNA repair

Credit: Tom Ellenberger

Researchers say they’ve discovered “an intimate link” between RUNX genes and Fanconi anemia, a finding that also has implications for treating acute myeloid leukemia (AML).

The group found that RUNX1 and RUNX3 interact with Fanconi anemia group D2 (FANCD2), a protein involved in the repair of DNA damage.

The RUNX proteins facilitate the recruitment of FANCD2 to sites of DNA damage in both Fanconi anemia and AML.

Motomi Osato, MD, PhD, of the Cancer Science Institute of Singapore, and his colleagues recounted these findings in Cell Reports.

The researchers began by studying RUNX deficiency in mice. They found that knockdown of both RUNX1 and RUNX3 led to bone marrow failure or myeloproliferative disorders in the mice.

These clinical manifestations are seen in inherited bone marrow failure syndromes such as Fanconi anemia, which is caused by the disruption of gene products that participate in the repair of DNA interstrand crosslinks (ICLs).

With this in mind, the researchers decided to investigate RUNX function in the ICL repair pathway. And they found RUNX proteins play a critical role in the pathway by facilitating the recruitment of FANCD2 to sites of DNA damage.

To explore the clinical relevance of RUNX participation in DNA damage repair, the team conducted experiments in Kasumi-1 and SKNO-1 cells. These AML cell lines express RUNX1-ETO, which is thought to suppress the expression and/or function of RUNX1 and RUNX3 simultaneously.

The researchers showed that Kasumi-1 and SKNO-1 cells were sensitive to the ICL-inducing agent mytomycin C, and knocking down RUNX1-ETO reduced this sensitivity. Depleting RUNX1-ETO also led to increased FANCD2 recruitment to chromatin.

The team said these results suggest that RUNX1-ETO might repress FANCD2 foci formation and ICL repair in AML cells. And they predicted that RUNX dysfunction would sensitize the cells to PARP inhibitors.

So they tested 2 PARP inhibitors—olaparib and rucaparib—in Kasumi-1 cells and observed sensitivity to both drugs. Knocking down RUNX1-ETO partially reduced this sensitivity, while adding mytomycin C increased sensitivity.

“PARP inhibitors have been with us for quite some time, but nobody has realized their application for leukemia,” Dr Osato said. “Our study has shed light on the possibility of a more effective treatment using a combined therapy with PARP inhibitors, which can potentially be extended to other types of common cancers.”

The researchers are now conducting additional drug testing in xenograft models.

DNA repair

Credit: Tom Ellenberger

Researchers say they’ve discovered “an intimate link” between RUNX genes and Fanconi anemia, a finding that also has implications for treating acute myeloid leukemia (AML).

The group found that RUNX1 and RUNX3 interact with Fanconi anemia group D2 (FANCD2), a protein involved in the repair of DNA damage.

The RUNX proteins facilitate the recruitment of FANCD2 to sites of DNA damage in both Fanconi anemia and AML.

Motomi Osato, MD, PhD, of the Cancer Science Institute of Singapore, and his colleagues recounted these findings in Cell Reports.

The researchers began by studying RUNX deficiency in mice. They found that knockdown of both RUNX1 and RUNX3 led to bone marrow failure or myeloproliferative disorders in the mice.

These clinical manifestations are seen in inherited bone marrow failure syndromes such as Fanconi anemia, which is caused by the disruption of gene products that participate in the repair of DNA interstrand crosslinks (ICLs).

With this in mind, the researchers decided to investigate RUNX function in the ICL repair pathway. And they found RUNX proteins play a critical role in the pathway by facilitating the recruitment of FANCD2 to sites of DNA damage.

To explore the clinical relevance of RUNX participation in DNA damage repair, the team conducted experiments in Kasumi-1 and SKNO-1 cells. These AML cell lines express RUNX1-ETO, which is thought to suppress the expression and/or function of RUNX1 and RUNX3 simultaneously.

The researchers showed that Kasumi-1 and SKNO-1 cells were sensitive to the ICL-inducing agent mytomycin C, and knocking down RUNX1-ETO reduced this sensitivity. Depleting RUNX1-ETO also led to increased FANCD2 recruitment to chromatin.

The team said these results suggest that RUNX1-ETO might repress FANCD2 foci formation and ICL repair in AML cells. And they predicted that RUNX dysfunction would sensitize the cells to PARP inhibitors.

So they tested 2 PARP inhibitors—olaparib and rucaparib—in Kasumi-1 cells and observed sensitivity to both drugs. Knocking down RUNX1-ETO partially reduced this sensitivity, while adding mytomycin C increased sensitivity.

“PARP inhibitors have been with us for quite some time, but nobody has realized their application for leukemia,” Dr Osato said. “Our study has shed light on the possibility of a more effective treatment using a combined therapy with PARP inhibitors, which can potentially be extended to other types of common cancers.”

The researchers are now conducting additional drug testing in xenograft models.

DNA repair

Credit: Tom Ellenberger

Researchers say they’ve discovered “an intimate link” between RUNX genes and Fanconi anemia, a finding that also has implications for treating acute myeloid leukemia (AML).

The group found that RUNX1 and RUNX3 interact with Fanconi anemia group D2 (FANCD2), a protein involved in the repair of DNA damage.

The RUNX proteins facilitate the recruitment of FANCD2 to sites of DNA damage in both Fanconi anemia and AML.

Motomi Osato, MD, PhD, of the Cancer Science Institute of Singapore, and his colleagues recounted these findings in Cell Reports.

The researchers began by studying RUNX deficiency in mice. They found that knockdown of both RUNX1 and RUNX3 led to bone marrow failure or myeloproliferative disorders in the mice.

These clinical manifestations are seen in inherited bone marrow failure syndromes such as Fanconi anemia, which is caused by the disruption of gene products that participate in the repair of DNA interstrand crosslinks (ICLs).

With this in mind, the researchers decided to investigate RUNX function in the ICL repair pathway. And they found RUNX proteins play a critical role in the pathway by facilitating the recruitment of FANCD2 to sites of DNA damage.

To explore the clinical relevance of RUNX participation in DNA damage repair, the team conducted experiments in Kasumi-1 and SKNO-1 cells. These AML cell lines express RUNX1-ETO, which is thought to suppress the expression and/or function of RUNX1 and RUNX3 simultaneously.

The researchers showed that Kasumi-1 and SKNO-1 cells were sensitive to the ICL-inducing agent mytomycin C, and knocking down RUNX1-ETO reduced this sensitivity. Depleting RUNX1-ETO also led to increased FANCD2 recruitment to chromatin.

The team said these results suggest that RUNX1-ETO might repress FANCD2 foci formation and ICL repair in AML cells. And they predicted that RUNX dysfunction would sensitize the cells to PARP inhibitors.

So they tested 2 PARP inhibitors—olaparib and rucaparib—in Kasumi-1 cells and observed sensitivity to both drugs. Knocking down RUNX1-ETO partially reduced this sensitivity, while adding mytomycin C increased sensitivity.

“PARP inhibitors have been with us for quite some time, but nobody has realized their application for leukemia,” Dr Osato said. “Our study has shed light on the possibility of a more effective treatment using a combined therapy with PARP inhibitors, which can potentially be extended to other types of common cancers.”

The researchers are now conducting additional drug testing in xenograft models.