HT Staff

Saline solution

In an attempt to alleviate the shortage of saline (0.9% sodium chloride injection) in the US, the Food and Drug Administration (FDA) is allowing saline products to be imported from Norway.

The company importing the products is Fresenius Kabi USA. The FDA inspected the company’s Norway manufacturing facility and found the site meets FDA standards.

So Fresenius Kabi has begun importing Sodium Chloride 0.9% Freeflex Injection Solution for Intravenous Infusion.

The European product contains the same active ingredient in the same concentration as the 0.9% sodium chloride injection products approved in the US.

For a complete list of all the Fresenius Kabi saline products, as well as a list of differences between the European and US prescribing information, see the “Dear Healthcare Professional” letter posted on the FDA website.

The FDA is asking that healthcare professionals contact Fresenius Kabi USA directly to obtain saline products. The company’s customer service number is 1-888-386-1300.

The FDA concedes that, while the shipments from Norway will help, they will not resolve the saline shortage. However, the agency says it is working closely with manufacturers to meet the needs for saline across the US.

Saline solution

In an attempt to alleviate the shortage of saline (0.9% sodium chloride injection) in the US, the Food and Drug Administration (FDA) is allowing saline products to be imported from Norway.

The company importing the products is Fresenius Kabi USA. The FDA inspected the company’s Norway manufacturing facility and found the site meets FDA standards.

So Fresenius Kabi has begun importing Sodium Chloride 0.9% Freeflex Injection Solution for Intravenous Infusion.

The European product contains the same active ingredient in the same concentration as the 0.9% sodium chloride injection products approved in the US.

For a complete list of all the Fresenius Kabi saline products, as well as a list of differences between the European and US prescribing information, see the “Dear Healthcare Professional” letter posted on the FDA website.

The FDA is asking that healthcare professionals contact Fresenius Kabi USA directly to obtain saline products. The company’s customer service number is 1-888-386-1300.

The FDA concedes that, while the shipments from Norway will help, they will not resolve the saline shortage. However, the agency says it is working closely with manufacturers to meet the needs for saline across the US.

Saline solution

In an attempt to alleviate the shortage of saline (0.9% sodium chloride injection) in the US, the Food and Drug Administration (FDA) is allowing saline products to be imported from Norway.

The company importing the products is Fresenius Kabi USA. The FDA inspected the company’s Norway manufacturing facility and found the site meets FDA standards.

So Fresenius Kabi has begun importing Sodium Chloride 0.9% Freeflex Injection Solution for Intravenous Infusion.

The European product contains the same active ingredient in the same concentration as the 0.9% sodium chloride injection products approved in the US.

For a complete list of all the Fresenius Kabi saline products, as well as a list of differences between the European and US prescribing information, see the “Dear Healthcare Professional” letter posted on the FDA website.

The FDA is asking that healthcare professionals contact Fresenius Kabi USA directly to obtain saline products. The company’s customer service number is 1-888-386-1300.

The FDA concedes that, while the shipments from Norway will help, they will not resolve the saline shortage. However, the agency says it is working closely with manufacturers to meet the needs for saline across the US.

Thrombus

Credit: Andre E.X. Brown

WASHINGTON, DC—A new analysis suggests cangrelor can reduce the risk of stent thrombosis in patients undergoing percutaneous coronary intervention (PCI), when compared to clopidogrel.

In fact, cangrelor was an independent predictor of freedom from stent thrombosis at 30 days after PCI.

These results, obtained by analyzing patients from the CHAMPION PHOENIX trial, were presented at the American College of Cardiology’s 63rd Annual Scientific Session & Expo (presentation 2105-290).

CHAMPION PHOENIX was a prospective, double-blind trial that included 11,145 patients. They were randomized to receive intravenous cangrelor or oral clopidogrel at the time of PCI.

In a previous analysis of the trial data, researchers found that cangrelor reduced the overall odds of complications from stenting procedures—including death, myocardial infarction, ischemia-driven revascularization, and stent thrombosis—compared to clopidogrel. However, cangrelor also increased the risk of major and minor bleeding.

In the new analysis, an independent core laboratory blinded to the treatment performed angiographic analysis in 10,939 of the patients. The researchers defined stent thrombosis as the occurrence of intraprocedural stent thrombosis (IPST) or ARC-defined stent thrombosis (definite or probable).

Stent thrombosis occurred in 120 patients (1.1%) at 48 hours after PCI and in 175 patients (1.6%) at 30 days. The occurrence of stent thrombosis at 48 hours and 30 days was associated with a marked increase in 30-day mortality, with odds ratios (ORs) of 15.3 (P<0.001) and 55.2 (P<0.001), respectively.

IPST, ARC acute stent thrombosis (≤ 24 hrs), and ARC subacute stent thrombosis (1-30 days) occurred in 89 (0.8%), 32 (0.3%), and 60 (0.5%) patients, respectively.

Each type of stent thrombosis was associated with an increase in 30-day mortality. The ORs were 17.4 for IPST (P<0.001), 43.3 for ARC acute stent thrombosis (P<0.001), and 189.1 for ARC subacute stent thrombosis (P<0.001).

“Regardless of the exact type of stent thrombosis, it remains associated with a high rate of death,” said investigator Deepak L. Bhatt, MD, MPH, a professor at Harvard Medical School and co-chair of the CHAMPION program.

However, patients who received cangrelor were less likely than those treated with clopidogrel to develop stent thrombosis, both at 48 hours and at 30 days.

At 48 hours, stent thrombosis had occurred in 0.8% and 1.4% of patients, respectively (P=0.01). And at 30 days, stent thrombosis had occurred in 1.3% and 1.9%, respectively (P=0.01).

Cangrelor appeared to be more effective than clopidogrel at preventing all types of stent thrombosis, although the difference was only statistically significant for IPST.

IPST occurred in 0.6% and 1.0% of patients, respectively (P=0.04). Acute ARC stent thrombosis occurred in 0.2% and 0.4%, respectively (P=0.8). And subacute ARC stent thrombosis occurred in 0.5% and 0.6%, respectively (P=0.60).

Multivariable analysis suggested the use of cangrelor was as an independent predictor of freedom from stent thrombosis at 30 days.

The CHAMPION PHOENIX trial was funded by The Medicines Company, makers of cangrelor.

Thrombus

Credit: Andre E.X. Brown

WASHINGTON, DC—A new analysis suggests cangrelor can reduce the risk of stent thrombosis in patients undergoing percutaneous coronary intervention (PCI), when compared to clopidogrel.

In fact, cangrelor was an independent predictor of freedom from stent thrombosis at 30 days after PCI.

These results, obtained by analyzing patients from the CHAMPION PHOENIX trial, were presented at the American College of Cardiology’s 63rd Annual Scientific Session & Expo (presentation 2105-290).

CHAMPION PHOENIX was a prospective, double-blind trial that included 11,145 patients. They were randomized to receive intravenous cangrelor or oral clopidogrel at the time of PCI.

In a previous analysis of the trial data, researchers found that cangrelor reduced the overall odds of complications from stenting procedures—including death, myocardial infarction, ischemia-driven revascularization, and stent thrombosis—compared to clopidogrel. However, cangrelor also increased the risk of major and minor bleeding.

In the new analysis, an independent core laboratory blinded to the treatment performed angiographic analysis in 10,939 of the patients. The researchers defined stent thrombosis as the occurrence of intraprocedural stent thrombosis (IPST) or ARC-defined stent thrombosis (definite or probable).

Stent thrombosis occurred in 120 patients (1.1%) at 48 hours after PCI and in 175 patients (1.6%) at 30 days. The occurrence of stent thrombosis at 48 hours and 30 days was associated with a marked increase in 30-day mortality, with odds ratios (ORs) of 15.3 (P<0.001) and 55.2 (P<0.001), respectively.

IPST, ARC acute stent thrombosis (≤ 24 hrs), and ARC subacute stent thrombosis (1-30 days) occurred in 89 (0.8%), 32 (0.3%), and 60 (0.5%) patients, respectively.

Each type of stent thrombosis was associated with an increase in 30-day mortality. The ORs were 17.4 for IPST (P<0.001), 43.3 for ARC acute stent thrombosis (P<0.001), and 189.1 for ARC subacute stent thrombosis (P<0.001).

“Regardless of the exact type of stent thrombosis, it remains associated with a high rate of death,” said investigator Deepak L. Bhatt, MD, MPH, a professor at Harvard Medical School and co-chair of the CHAMPION program.

However, patients who received cangrelor were less likely than those treated with clopidogrel to develop stent thrombosis, both at 48 hours and at 30 days.

At 48 hours, stent thrombosis had occurred in 0.8% and 1.4% of patients, respectively (P=0.01). And at 30 days, stent thrombosis had occurred in 1.3% and 1.9%, respectively (P=0.01).

Cangrelor appeared to be more effective than clopidogrel at preventing all types of stent thrombosis, although the difference was only statistically significant for IPST.

IPST occurred in 0.6% and 1.0% of patients, respectively (P=0.04). Acute ARC stent thrombosis occurred in 0.2% and 0.4%, respectively (P=0.8). And subacute ARC stent thrombosis occurred in 0.5% and 0.6%, respectively (P=0.60).

Multivariable analysis suggested the use of cangrelor was as an independent predictor of freedom from stent thrombosis at 30 days.

The CHAMPION PHOENIX trial was funded by The Medicines Company, makers of cangrelor.

Thrombus

Credit: Andre E.X. Brown

WASHINGTON, DC—A new analysis suggests cangrelor can reduce the risk of stent thrombosis in patients undergoing percutaneous coronary intervention (PCI), when compared to clopidogrel.

In fact, cangrelor was an independent predictor of freedom from stent thrombosis at 30 days after PCI.

These results, obtained by analyzing patients from the CHAMPION PHOENIX trial, were presented at the American College of Cardiology’s 63rd Annual Scientific Session & Expo (presentation 2105-290).

CHAMPION PHOENIX was a prospective, double-blind trial that included 11,145 patients. They were randomized to receive intravenous cangrelor or oral clopidogrel at the time of PCI.

In a previous analysis of the trial data, researchers found that cangrelor reduced the overall odds of complications from stenting procedures—including death, myocardial infarction, ischemia-driven revascularization, and stent thrombosis—compared to clopidogrel. However, cangrelor also increased the risk of major and minor bleeding.

In the new analysis, an independent core laboratory blinded to the treatment performed angiographic analysis in 10,939 of the patients. The researchers defined stent thrombosis as the occurrence of intraprocedural stent thrombosis (IPST) or ARC-defined stent thrombosis (definite or probable).

Stent thrombosis occurred in 120 patients (1.1%) at 48 hours after PCI and in 175 patients (1.6%) at 30 days. The occurrence of stent thrombosis at 48 hours and 30 days was associated with a marked increase in 30-day mortality, with odds ratios (ORs) of 15.3 (P<0.001) and 55.2 (P<0.001), respectively.

IPST, ARC acute stent thrombosis (≤ 24 hrs), and ARC subacute stent thrombosis (1-30 days) occurred in 89 (0.8%), 32 (0.3%), and 60 (0.5%) patients, respectively.

Each type of stent thrombosis was associated with an increase in 30-day mortality. The ORs were 17.4 for IPST (P<0.001), 43.3 for ARC acute stent thrombosis (P<0.001), and 189.1 for ARC subacute stent thrombosis (P<0.001).

“Regardless of the exact type of stent thrombosis, it remains associated with a high rate of death,” said investigator Deepak L. Bhatt, MD, MPH, a professor at Harvard Medical School and co-chair of the CHAMPION program.

However, patients who received cangrelor were less likely than those treated with clopidogrel to develop stent thrombosis, both at 48 hours and at 30 days.

At 48 hours, stent thrombosis had occurred in 0.8% and 1.4% of patients, respectively (P=0.01). And at 30 days, stent thrombosis had occurred in 1.3% and 1.9%, respectively (P=0.01).

Cangrelor appeared to be more effective than clopidogrel at preventing all types of stent thrombosis, although the difference was only statistically significant for IPST.

IPST occurred in 0.6% and 1.0% of patients, respectively (P=0.04). Acute ARC stent thrombosis occurred in 0.2% and 0.4%, respectively (P=0.8). And subacute ARC stent thrombosis occurred in 0.5% and 0.6%, respectively (P=0.60).

Multivariable analysis suggested the use of cangrelor was as an independent predictor of freedom from stent thrombosis at 30 days.

The CHAMPION PHOENIX trial was funded by The Medicines Company, makers of cangrelor.

 

 

Syringe

 

The European Commission (EC) has approved a subcutaneous (SC) formulation of rituximab (MabThera) to treat patients with follicular lymphoma or diffuse large B-cell lymphoma.

This formulation allows for 5-minute administration, a significant decrease over the 2.5-hour infusion time required to administer intravenous (IV) rituximab.

The drug’s maker, Roche, plans to begin launching SC rituximab in a number of European markets this year.

The EC’s approval of this formulation was primarily based on data from the SABRINA trial, which was recently published in The Lancet Oncology and funded by Roche.

In this phase 3 trial, researchers compared 3-week cycles of fixed-dose, SC rituximab to IV rituximab. They enrolled 127 patients with previously untreated, grade 1-3a, CD20-positive follicular lymphoma.

Patients were randomized to receive IV rituximab (375 mg/m²) or SC rituximab (1400 mg). After randomization, they received 1 induction dose of IV rituximab in cycle 1 and then their allocated treatment for cycles 2 through 8. Patients with a complete or partial response continued their treatment as maintenance every 8 weeks.

The study’s primary endpoint was the ratio of observed rituximab serum trough concentrations (C_trough) between the 2 groups at cycle 7.

Pharmacokinetic data were available for 75% of patients (48/64) in the IV arm and 86% of the patients (54/63) in the SC arm.

An analysis of these data suggested SC rituximab was non-inferior to the IV formulation. The geometric mean C_trough was 83.13 μg/mL in the IV arm and 134.58 μg/mL in the SC arm (ratio, 1.62).

The rate of adverse events was similar between the 2 arms, occurring in 88% (57/65) of patients in the IV arm and 92% (57/62) of patients in the SC arm. Grade 3 or higher adverse events occurred in 46% (n=30) and 47% (n=29) of patients, respectively.

The most common grade 3 or higher adverse event in both arms was neutropenia. It occurred in 22% (n=14) of patients in the IV arm and 26% (n=16) in the SC arm.

Adverse events related to administration were mostly grade 1-2. And they occurred more often in the SC arm than in the IV arm, in 50% (n=31) and 32% (n=21) of patients, respectively.

The researchers said these results suggest the SC formulation of rituximab is non-inferior to the IV formulation and poses no new safety concerns.

 

 

Syringe

 

The European Commission (EC) has approved a subcutaneous (SC) formulation of rituximab (MabThera) to treat patients with follicular lymphoma or diffuse large B-cell lymphoma.

This formulation allows for 5-minute administration, a significant decrease over the 2.5-hour infusion time required to administer intravenous (IV) rituximab.

The drug’s maker, Roche, plans to begin launching SC rituximab in a number of European markets this year.

The EC’s approval of this formulation was primarily based on data from the SABRINA trial, which was recently published in The Lancet Oncology and funded by Roche.

In this phase 3 trial, researchers compared 3-week cycles of fixed-dose, SC rituximab to IV rituximab. They enrolled 127 patients with previously untreated, grade 1-3a, CD20-positive follicular lymphoma.

Patients were randomized to receive IV rituximab (375 mg/m²) or SC rituximab (1400 mg). After randomization, they received 1 induction dose of IV rituximab in cycle 1 and then their allocated treatment for cycles 2 through 8. Patients with a complete or partial response continued their treatment as maintenance every 8 weeks.

The study’s primary endpoint was the ratio of observed rituximab serum trough concentrations (C_trough) between the 2 groups at cycle 7.

Pharmacokinetic data were available for 75% of patients (48/64) in the IV arm and 86% of the patients (54/63) in the SC arm.

An analysis of these data suggested SC rituximab was non-inferior to the IV formulation. The geometric mean C_trough was 83.13 μg/mL in the IV arm and 134.58 μg/mL in the SC arm (ratio, 1.62).

The rate of adverse events was similar between the 2 arms, occurring in 88% (57/65) of patients in the IV arm and 92% (57/62) of patients in the SC arm. Grade 3 or higher adverse events occurred in 46% (n=30) and 47% (n=29) of patients, respectively.

The most common grade 3 or higher adverse event in both arms was neutropenia. It occurred in 22% (n=14) of patients in the IV arm and 26% (n=16) in the SC arm.

Adverse events related to administration were mostly grade 1-2. And they occurred more often in the SC arm than in the IV arm, in 50% (n=31) and 32% (n=21) of patients, respectively.

The researchers said these results suggest the SC formulation of rituximab is non-inferior to the IV formulation and poses no new safety concerns.

 

 

Syringe

 

The European Commission (EC) has approved a subcutaneous (SC) formulation of rituximab (MabThera) to treat patients with follicular lymphoma or diffuse large B-cell lymphoma.

This formulation allows for 5-minute administration, a significant decrease over the 2.5-hour infusion time required to administer intravenous (IV) rituximab.

The drug’s maker, Roche, plans to begin launching SC rituximab in a number of European markets this year.

The EC’s approval of this formulation was primarily based on data from the SABRINA trial, which was recently published in The Lancet Oncology and funded by Roche.

In this phase 3 trial, researchers compared 3-week cycles of fixed-dose, SC rituximab to IV rituximab. They enrolled 127 patients with previously untreated, grade 1-3a, CD20-positive follicular lymphoma.

Patients were randomized to receive IV rituximab (375 mg/m²) or SC rituximab (1400 mg). After randomization, they received 1 induction dose of IV rituximab in cycle 1 and then their allocated treatment for cycles 2 through 8. Patients with a complete or partial response continued their treatment as maintenance every 8 weeks.

The study’s primary endpoint was the ratio of observed rituximab serum trough concentrations (C_trough) between the 2 groups at cycle 7.

Pharmacokinetic data were available for 75% of patients (48/64) in the IV arm and 86% of the patients (54/63) in the SC arm.

An analysis of these data suggested SC rituximab was non-inferior to the IV formulation. The geometric mean C_trough was 83.13 μg/mL in the IV arm and 134.58 μg/mL in the SC arm (ratio, 1.62).

The rate of adverse events was similar between the 2 arms, occurring in 88% (57/65) of patients in the IV arm and 92% (57/62) of patients in the SC arm. Grade 3 or higher adverse events occurred in 46% (n=30) and 47% (n=29) of patients, respectively.

The most common grade 3 or higher adverse event in both arms was neutropenia. It occurred in 22% (n=14) of patients in the IV arm and 26% (n=16) in the SC arm.

Adverse events related to administration were mostly grade 1-2. And they occurred more often in the SC arm than in the IV arm, in 50% (n=31) and 32% (n=21) of patients, respectively.

The researchers said these results suggest the SC formulation of rituximab is non-inferior to the IV formulation and poses no new safety concerns.

Cell culture in a petri dish

Results of a pilot study suggest safe transplantation of spermatogonial stem cells (SSCs) may be possible, potentially bringing us one step closer to ensuring fertility preservation in young boys with cancer.

Investigators found they could culture a large amount of SSCs using testicular tissue from boys with acute lymphoblastic leukemia (ALL).

And the ALL cells did not survive the culture process.

The researchers reported these results in Fertility and Sterility.

“Our study addressed an important safety issue—whether cancer cells that might be present in testicular tissue samples can survive the process to replicate the sperm-producing stem cells,” said study author Hooman Sadri-Ardekani, MD, PhD, of Wake Forest Baptist Medical Center in Winston-Salem, North Carolina.

“This is an important consideration because of the potential to re-introduce cancer into the patient. The research, which involved one of the most common childhood cancers, shows that the cancer cells were eliminated. Based on these findings, we recommend that all boys with cancer be offered the option of storing testicular tissue for possible future clinical use.”

Previous research had shown that up to 30% of boys with ALL had cancer cells in their testicular tissue. In several studies, researchers attempted to eliminate cancer cells from biopsy tissue, but the results varied.

So Dr Sadri-Ardekani and his colleagues decided to investigate whether cancer cells would survive the protocol they had developed to reproduce SSCs from a small tissue biopsy.

This process multiplies the original SSCs by 18,000-fold so there are enough cells to transplant back into the patient when he reaches adulthood.

The investigators tested the method using samples from 3 ALL patients. The team cultured the ALL cells alone and at various concentrations in combination with testicular cells.

The ALL cells cultured alone did not survive beyond 14 days. But the testicular cells cultured in parallel survived and continue to proliferate well after 8 weeks.

At 10 to 16 days, the ALL cells cultured in combination had begun to die off. The cells were undetectable in cultures from 2 of the patients that had an initial ALL concentration of 0.04%, 0.4%, or 4%.

At 20 to 26 days, ALL cells were undetectable in all cultures, even those with an initial concentration of 40% ALL cells.

“This pilot study showed that the culture system not only allowed for efficient propagation of sperm stem cells but also eliminated ALL cells,” Dr Sadri-Ardekani said.

SSC transplants have not yet been attempted in humans, but they have been performed successfully in several species of animals, including monkeys.

Dr Sadri-Ardekani noted that before we can perform SSC transplants in patients, additional research is needed, particularly, research investigating whether other types of leukemia cells will also be eliminated in the cell-propagation process.

Cell culture in a petri dish

Results of a pilot study suggest safe transplantation of spermatogonial stem cells (SSCs) may be possible, potentially bringing us one step closer to ensuring fertility preservation in young boys with cancer.

Investigators found they could culture a large amount of SSCs using testicular tissue from boys with acute lymphoblastic leukemia (ALL).

And the ALL cells did not survive the culture process.

The researchers reported these results in Fertility and Sterility.

“Our study addressed an important safety issue—whether cancer cells that might be present in testicular tissue samples can survive the process to replicate the sperm-producing stem cells,” said study author Hooman Sadri-Ardekani, MD, PhD, of Wake Forest Baptist Medical Center in Winston-Salem, North Carolina.

“This is an important consideration because of the potential to re-introduce cancer into the patient. The research, which involved one of the most common childhood cancers, shows that the cancer cells were eliminated. Based on these findings, we recommend that all boys with cancer be offered the option of storing testicular tissue for possible future clinical use.”

Previous research had shown that up to 30% of boys with ALL had cancer cells in their testicular tissue. In several studies, researchers attempted to eliminate cancer cells from biopsy tissue, but the results varied.

So Dr Sadri-Ardekani and his colleagues decided to investigate whether cancer cells would survive the protocol they had developed to reproduce SSCs from a small tissue biopsy.

This process multiplies the original SSCs by 18,000-fold so there are enough cells to transplant back into the patient when he reaches adulthood.

The investigators tested the method using samples from 3 ALL patients. The team cultured the ALL cells alone and at various concentrations in combination with testicular cells.

The ALL cells cultured alone did not survive beyond 14 days. But the testicular cells cultured in parallel survived and continue to proliferate well after 8 weeks.

At 10 to 16 days, the ALL cells cultured in combination had begun to die off. The cells were undetectable in cultures from 2 of the patients that had an initial ALL concentration of 0.04%, 0.4%, or 4%.

At 20 to 26 days, ALL cells were undetectable in all cultures, even those with an initial concentration of 40% ALL cells.

“This pilot study showed that the culture system not only allowed for efficient propagation of sperm stem cells but also eliminated ALL cells,” Dr Sadri-Ardekani said.

SSC transplants have not yet been attempted in humans, but they have been performed successfully in several species of animals, including monkeys.

Dr Sadri-Ardekani noted that before we can perform SSC transplants in patients, additional research is needed, particularly, research investigating whether other types of leukemia cells will also be eliminated in the cell-propagation process.

Cell culture in a petri dish

Results of a pilot study suggest safe transplantation of spermatogonial stem cells (SSCs) may be possible, potentially bringing us one step closer to ensuring fertility preservation in young boys with cancer.

Investigators found they could culture a large amount of SSCs using testicular tissue from boys with acute lymphoblastic leukemia (ALL).

And the ALL cells did not survive the culture process.

The researchers reported these results in Fertility and Sterility.

“Our study addressed an important safety issue—whether cancer cells that might be present in testicular tissue samples can survive the process to replicate the sperm-producing stem cells,” said study author Hooman Sadri-Ardekani, MD, PhD, of Wake Forest Baptist Medical Center in Winston-Salem, North Carolina.

“This is an important consideration because of the potential to re-introduce cancer into the patient. The research, which involved one of the most common childhood cancers, shows that the cancer cells were eliminated. Based on these findings, we recommend that all boys with cancer be offered the option of storing testicular tissue for possible future clinical use.”

Previous research had shown that up to 30% of boys with ALL had cancer cells in their testicular tissue. In several studies, researchers attempted to eliminate cancer cells from biopsy tissue, but the results varied.

So Dr Sadri-Ardekani and his colleagues decided to investigate whether cancer cells would survive the protocol they had developed to reproduce SSCs from a small tissue biopsy.

This process multiplies the original SSCs by 18,000-fold so there are enough cells to transplant back into the patient when he reaches adulthood.

The investigators tested the method using samples from 3 ALL patients. The team cultured the ALL cells alone and at various concentrations in combination with testicular cells.

The ALL cells cultured alone did not survive beyond 14 days. But the testicular cells cultured in parallel survived and continue to proliferate well after 8 weeks.

At 10 to 16 days, the ALL cells cultured in combination had begun to die off. The cells were undetectable in cultures from 2 of the patients that had an initial ALL concentration of 0.04%, 0.4%, or 4%.

At 20 to 26 days, ALL cells were undetectable in all cultures, even those with an initial concentration of 40% ALL cells.

“This pilot study showed that the culture system not only allowed for efficient propagation of sperm stem cells but also eliminated ALL cells,” Dr Sadri-Ardekani said.

SSC transplants have not yet been attempted in humans, but they have been performed successfully in several species of animals, including monkeys.

Dr Sadri-Ardekani noted that before we can perform SSC transplants in patients, additional research is needed, particularly, research investigating whether other types of leukemia cells will also be eliminated in the cell-propagation process.

Lone star tick

Credit: CDC

Health officials have reported 6 new cases of Heartland virus disease—5 in Missouri and 1 in Tennessee.

These cases, discovered in 2012 and 2013, add to the 2 cases discovered in 2009 and are described in the Centers for Disease Control and Prevention (CDC) Morbidity and Mortality Weekly Report.

The Heartland virus was first reported in 2 farmers in northwestern Missouri who were hospitalized in 2009 with what was thought to be ehrlichiosis, a tick-borne disease.

However, the patients failed to improve with treatment, and testing failed to confirm ehlrlichiosis.

Working with state and local partners, the CDC eventually identified the cause of the men’s illness: a previously unknown phlebovirus, now dubbed the Heartland virus.

Although we do not know for certain how patients are infected with the virus, research has suggested that ticks, namely lone star ticks, transmit it.

Ongoing investigations have uncovered 6 more cases of Heartland virus disease. All of the patients were white men older than 50 years of age. Five of them reported tick bites in the days or weeks before they fell ill.

Their symptoms started in May to September and included fever, fatigue, loss of appetite, headache, nausea, and muscle pain. The patients also had leukopenia and thrombocytopenia.

Four of the 6 patients were hospitalized. And 1 man, who suffered from other health conditions, died. It is not known if the Heartland virus was the cause of death or how much it contributed to his death.

The CDC has been working with the Missouri and Tennessee state health departments and other federal agencies to advance our understanding of Heartland virus disease by learning more about the patients who were infected, their illness, and their exposure to ticks.

The CDC aims to determine the symptoms and severity of the disease, where it is found, how people are being infected, and how to prevent infections.

CDC studies to date have shown that the Heartland virus is carried by lone star ticks, which are primarily found in the southeastern and eastern US.

Researchers hope additional studies can confirm whether ticks can spread the virus and reveal which other insects or animals may be involved in the transmission cycle. The CDC is also looking for the Heartland virus in other parts of the country to understand how widely it may be distributed.

“During the past 2 years, CDC has worked closely with state health departments, hospitals, and many experts from universities and other federal agencies to learn more about Heartland virus,” said Roger Nasci, PhD, chief of the CDC’s Arboviral Diseases Branch.

“By gathering information about the disease Heartland virus causes, and about how it’s spread to people, we hope to better understand the potential impact on the public’s health and how we can help protect people from this virus.”

The CDC developed the blood tests used to confirm the new cases of Heartland virus disease. CDC teams are working to further validate these tests and develop additional tests. The researchers hope to develop a diagnostic test that public health laboratories could use to test for the virus.

There is no specific treatment or vaccine for Heartland virus disease. However, supportive therapies such as intravenous fluids and fever reducers can relieve some symptoms of Heartland disease.

To reduce the risk of Heartland and other vector-borne diseases, the CDC recommends:

• Avoiding wooded and bushy areas with high grass and leaf litter
• Using insect repellent when outdoors
• Using products that contain permethrin on clothing
• Conducting a full-body tick check after spending time outdoors
• Bathing as soon as possible after coming indoors to wash off and more easily find any ticks
• Examining gear and pets, as ticks can “ride” into the home and attach to a person later.

For more information on the Heartland virus, visit the CDC website.

Lone star tick

Credit: CDC

Health officials have reported 6 new cases of Heartland virus disease—5 in Missouri and 1 in Tennessee.

These cases, discovered in 2012 and 2013, add to the 2 cases discovered in 2009 and are described in the Centers for Disease Control and Prevention (CDC) Morbidity and Mortality Weekly Report.

The Heartland virus was first reported in 2 farmers in northwestern Missouri who were hospitalized in 2009 with what was thought to be ehrlichiosis, a tick-borne disease.

However, the patients failed to improve with treatment, and testing failed to confirm ehlrlichiosis.

Working with state and local partners, the CDC eventually identified the cause of the men’s illness: a previously unknown phlebovirus, now dubbed the Heartland virus.

Although we do not know for certain how patients are infected with the virus, research has suggested that ticks, namely lone star ticks, transmit it.

Ongoing investigations have uncovered 6 more cases of Heartland virus disease. All of the patients were white men older than 50 years of age. Five of them reported tick bites in the days or weeks before they fell ill.

Their symptoms started in May to September and included fever, fatigue, loss of appetite, headache, nausea, and muscle pain. The patients also had leukopenia and thrombocytopenia.

Four of the 6 patients were hospitalized. And 1 man, who suffered from other health conditions, died. It is not known if the Heartland virus was the cause of death or how much it contributed to his death.

The CDC has been working with the Missouri and Tennessee state health departments and other federal agencies to advance our understanding of Heartland virus disease by learning more about the patients who were infected, their illness, and their exposure to ticks.

The CDC aims to determine the symptoms and severity of the disease, where it is found, how people are being infected, and how to prevent infections.

CDC studies to date have shown that the Heartland virus is carried by lone star ticks, which are primarily found in the southeastern and eastern US.

Researchers hope additional studies can confirm whether ticks can spread the virus and reveal which other insects or animals may be involved in the transmission cycle. The CDC is also looking for the Heartland virus in other parts of the country to understand how widely it may be distributed.

“During the past 2 years, CDC has worked closely with state health departments, hospitals, and many experts from universities and other federal agencies to learn more about Heartland virus,” said Roger Nasci, PhD, chief of the CDC’s Arboviral Diseases Branch.

“By gathering information about the disease Heartland virus causes, and about how it’s spread to people, we hope to better understand the potential impact on the public’s health and how we can help protect people from this virus.”

The CDC developed the blood tests used to confirm the new cases of Heartland virus disease. CDC teams are working to further validate these tests and develop additional tests. The researchers hope to develop a diagnostic test that public health laboratories could use to test for the virus.

There is no specific treatment or vaccine for Heartland virus disease. However, supportive therapies such as intravenous fluids and fever reducers can relieve some symptoms of Heartland disease.

To reduce the risk of Heartland and other vector-borne diseases, the CDC recommends:

• Avoiding wooded and bushy areas with high grass and leaf litter
• Using insect repellent when outdoors
• Using products that contain permethrin on clothing
• Conducting a full-body tick check after spending time outdoors
• Bathing as soon as possible after coming indoors to wash off and more easily find any ticks
• Examining gear and pets, as ticks can “ride” into the home and attach to a person later.

For more information on the Heartland virus, visit the CDC website.

Lone star tick

Credit: CDC

Health officials have reported 6 new cases of Heartland virus disease—5 in Missouri and 1 in Tennessee.

These cases, discovered in 2012 and 2013, add to the 2 cases discovered in 2009 and are described in the Centers for Disease Control and Prevention (CDC) Morbidity and Mortality Weekly Report.

The Heartland virus was first reported in 2 farmers in northwestern Missouri who were hospitalized in 2009 with what was thought to be ehrlichiosis, a tick-borne disease.

However, the patients failed to improve with treatment, and testing failed to confirm ehlrlichiosis.

Working with state and local partners, the CDC eventually identified the cause of the men’s illness: a previously unknown phlebovirus, now dubbed the Heartland virus.

Although we do not know for certain how patients are infected with the virus, research has suggested that ticks, namely lone star ticks, transmit it.

Ongoing investigations have uncovered 6 more cases of Heartland virus disease. All of the patients were white men older than 50 years of age. Five of them reported tick bites in the days or weeks before they fell ill.

Their symptoms started in May to September and included fever, fatigue, loss of appetite, headache, nausea, and muscle pain. The patients also had leukopenia and thrombocytopenia.

Four of the 6 patients were hospitalized. And 1 man, who suffered from other health conditions, died. It is not known if the Heartland virus was the cause of death or how much it contributed to his death.

The CDC has been working with the Missouri and Tennessee state health departments and other federal agencies to advance our understanding of Heartland virus disease by learning more about the patients who were infected, their illness, and their exposure to ticks.

The CDC aims to determine the symptoms and severity of the disease, where it is found, how people are being infected, and how to prevent infections.

CDC studies to date have shown that the Heartland virus is carried by lone star ticks, which are primarily found in the southeastern and eastern US.

Researchers hope additional studies can confirm whether ticks can spread the virus and reveal which other insects or animals may be involved in the transmission cycle. The CDC is also looking for the Heartland virus in other parts of the country to understand how widely it may be distributed.

“During the past 2 years, CDC has worked closely with state health departments, hospitals, and many experts from universities and other federal agencies to learn more about Heartland virus,” said Roger Nasci, PhD, chief of the CDC’s Arboviral Diseases Branch.

“By gathering information about the disease Heartland virus causes, and about how it’s spread to people, we hope to better understand the potential impact on the public’s health and how we can help protect people from this virus.”

The CDC developed the blood tests used to confirm the new cases of Heartland virus disease. CDC teams are working to further validate these tests and develop additional tests. The researchers hope to develop a diagnostic test that public health laboratories could use to test for the virus.

There is no specific treatment or vaccine for Heartland virus disease. However, supportive therapies such as intravenous fluids and fever reducers can relieve some symptoms of Heartland disease.

To reduce the risk of Heartland and other vector-borne diseases, the CDC recommends:

• Avoiding wooded and bushy areas with high grass and leaf litter
• Using insect repellent when outdoors
• Using products that contain permethrin on clothing
• Conducting a full-body tick check after spending time outdoors
• Bathing as soon as possible after coming indoors to wash off and more easily find any ticks
• Examining gear and pets, as ticks can “ride” into the home and attach to a person later.

For more information on the Heartland virus, visit the CDC website.

Vials and a syringe

The US Food and Drug Administration (FDA) has approved a recombinant factor IX Fc fusion protein  (rFIXFc, Alprolix) for use in adults and children with hemophilia B.

The product is intended to help control, prevent, or reduce the frequency of bleeding episodes that can occur day-to-day in patients with hemophilia B, as well as manage bleeding in patients undergoing surgery.

rFIXFc is made by fusing factor IX to the Fc portion of the IgG1 protein. Scientists believe this enables the product to use a naturally occurring pathway to prolong the time the therapy remains in the body.

The FDA’s approval is the second worldwide approval of rFIXFc. The product was recently authorized for use in Canada.

Researchers evaluated the safety, efficacy, and pharmacokinetics of rFIXFc in the phase 3 B-LONG study, which was funded by the product’s developers, Biogen Idec and Sobi.

Investigators tested rFIXFc in 123 males with hemophilia B who were at least 12 years of age. The patients were assigned to 1 of 4 treatment arms: weekly prophylaxis, individualized-interval prophylaxis, on-demand treatment to control bleeding, and perioperative management.

The overall median annualized bleeding rates were 2.95 for the weekly prophylaxis arm, 1.38 for the individualized-interval prophylaxis arm, and 17.69 in the on-demand treatment arm.

The overall median dosing interval with individualized-interval prophylaxis was 12.5 days. During the last 6 months of the study, the median dosing interval was 13.8 days.

Of the patients who received rFIXFc for perioperative management, 85.7% required a single injection of the product to maintain hemostasis during their operation. The median dose was 90.9 IU/kg per injection.

Most patients required 1 to 2 injections of the product the day before and the day of surgery. And most required 2 to 3 injections from days 1 to 3 after surgery.

The most common adverse events associated with rFIXFc (an incidence of ≥ 5% in a pooled analysis of treatment arms 1, 2, and 3) were nasopharyngitis, influenza, arthralgia, upper respiratory tract infection, hypertension, and headache.

The results of this study were released by Biogen Idec and Sobi in September 2012, presented at ISTH 2013, and published in NEJM in December 2013.

Vials and a syringe

The US Food and Drug Administration (FDA) has approved a recombinant factor IX Fc fusion protein  (rFIXFc, Alprolix) for use in adults and children with hemophilia B.

The product is intended to help control, prevent, or reduce the frequency of bleeding episodes that can occur day-to-day in patients with hemophilia B, as well as manage bleeding in patients undergoing surgery.

rFIXFc is made by fusing factor IX to the Fc portion of the IgG1 protein. Scientists believe this enables the product to use a naturally occurring pathway to prolong the time the therapy remains in the body.

The FDA’s approval is the second worldwide approval of rFIXFc. The product was recently authorized for use in Canada.

Researchers evaluated the safety, efficacy, and pharmacokinetics of rFIXFc in the phase 3 B-LONG study, which was funded by the product’s developers, Biogen Idec and Sobi.

Investigators tested rFIXFc in 123 males with hemophilia B who were at least 12 years of age. The patients were assigned to 1 of 4 treatment arms: weekly prophylaxis, individualized-interval prophylaxis, on-demand treatment to control bleeding, and perioperative management.

The overall median annualized bleeding rates were 2.95 for the weekly prophylaxis arm, 1.38 for the individualized-interval prophylaxis arm, and 17.69 in the on-demand treatment arm.

The overall median dosing interval with individualized-interval prophylaxis was 12.5 days. During the last 6 months of the study, the median dosing interval was 13.8 days.

Of the patients who received rFIXFc for perioperative management, 85.7% required a single injection of the product to maintain hemostasis during their operation. The median dose was 90.9 IU/kg per injection.

Most patients required 1 to 2 injections of the product the day before and the day of surgery. And most required 2 to 3 injections from days 1 to 3 after surgery.

The most common adverse events associated with rFIXFc (an incidence of ≥ 5% in a pooled analysis of treatment arms 1, 2, and 3) were nasopharyngitis, influenza, arthralgia, upper respiratory tract infection, hypertension, and headache.

The results of this study were released by Biogen Idec and Sobi in September 2012, presented at ISTH 2013, and published in NEJM in December 2013.

Vials and a syringe

The US Food and Drug Administration (FDA) has approved a recombinant factor IX Fc fusion protein  (rFIXFc, Alprolix) for use in adults and children with hemophilia B.

The product is intended to help control, prevent, or reduce the frequency of bleeding episodes that can occur day-to-day in patients with hemophilia B, as well as manage bleeding in patients undergoing surgery.

rFIXFc is made by fusing factor IX to the Fc portion of the IgG1 protein. Scientists believe this enables the product to use a naturally occurring pathway to prolong the time the therapy remains in the body.

The FDA’s approval is the second worldwide approval of rFIXFc. The product was recently authorized for use in Canada.

Researchers evaluated the safety, efficacy, and pharmacokinetics of rFIXFc in the phase 3 B-LONG study, which was funded by the product’s developers, Biogen Idec and Sobi.

Investigators tested rFIXFc in 123 males with hemophilia B who were at least 12 years of age. The patients were assigned to 1 of 4 treatment arms: weekly prophylaxis, individualized-interval prophylaxis, on-demand treatment to control bleeding, and perioperative management.

The overall median annualized bleeding rates were 2.95 for the weekly prophylaxis arm, 1.38 for the individualized-interval prophylaxis arm, and 17.69 in the on-demand treatment arm.

The overall median dosing interval with individualized-interval prophylaxis was 12.5 days. During the last 6 months of the study, the median dosing interval was 13.8 days.

Of the patients who received rFIXFc for perioperative management, 85.7% required a single injection of the product to maintain hemostasis during their operation. The median dose was 90.9 IU/kg per injection.

Most patients required 1 to 2 injections of the product the day before and the day of surgery. And most required 2 to 3 injections from days 1 to 3 after surgery.

The most common adverse events associated with rFIXFc (an incidence of ≥ 5% in a pooled analysis of treatment arms 1, 2, and 3) were nasopharyngitis, influenza, arthralgia, upper respiratory tract infection, hypertension, and headache.

The results of this study were released by Biogen Idec and Sobi in September 2012, presented at ISTH 2013, and published in NEJM in December 2013.

Nurse treating cancer patient

Credit: Rhoda Baer

A new report shows the rate of invasive cancer among US men and women dropped slightly from 2009 to 2010, and the most common cancers were solid tumor malignancies.

However, non-Hodgkin lymphoma (NHL) consistently rated among the top 10 most common cancers, regardless of patient gender or race.

The report was prepared by the Centers for Disease Control and Prevention (CDC) and appears in the current Morbidity and Mortality Weekly Report.

Researchers analyzed new cases of invasive cancers diagnosed in 2010 and reported to the CDC’s National Program of Cancer Registries and the National Cancer Institute’s Surveillance, Epidemiology and Results Program.

Data from all states (except Arkansas and Minnesota) and the District of Columbia were included in the analysis, which covered 97% of the US population.

The researchers found the rates of invasive cancer cases dropped from 459 per 100,000 people in 2009 to 446 per 100,000 in 2010.

Cancer rates were higher among men (503 per 100,000) than women (405 per 100,000). In all, there were 745,383 cases reported among men and 711,113 among women in 2010.

The highest rates were for cancers of the prostate (126 per 100,000), female breast (119 per 100,000), lung and bronchus (62 per 100,000), and colon and rectum (40 per 100,000). Together, these accounted for half of all cancer cases in the US.

However, hematologic malignancies were fairly common as well. NHL was the 6th most common cancer for men of all races/ethnicities except Hispanic. For this group, NHL was the 4th most common cancer.

NHL was the 7th most common cancer for black and white women and 6th for the remaining groups, which included American Indian/Alaskan native, Asian/Pacific Islander, and Hispanic women.

Leukemia and myeloma were also among the top 10 most common invasive cancers for certain patients.

Leukemia was the 9th most common cancer for Hispanic and white men and the 10th for American Indian/Alaskan Native women. Myeloma was the 8th most common cancer for black women.

Overall, cancer rates were highest among black patients (455 per 100,000), followed by whites (445 per 100,000), Hispanics (344 per 100,000), Asian/Pacific Islanders (289 per 100,000), and American Indians/Alaskan Natives (270 per 100,000).

Nurse treating cancer patient

Credit: Rhoda Baer

A new report shows the rate of invasive cancer among US men and women dropped slightly from 2009 to 2010, and the most common cancers were solid tumor malignancies.

However, non-Hodgkin lymphoma (NHL) consistently rated among the top 10 most common cancers, regardless of patient gender or race.

The report was prepared by the Centers for Disease Control and Prevention (CDC) and appears in the current Morbidity and Mortality Weekly Report.

Researchers analyzed new cases of invasive cancers diagnosed in 2010 and reported to the CDC’s National Program of Cancer Registries and the National Cancer Institute’s Surveillance, Epidemiology and Results Program.

Data from all states (except Arkansas and Minnesota) and the District of Columbia were included in the analysis, which covered 97% of the US population.

The researchers found the rates of invasive cancer cases dropped from 459 per 100,000 people in 2009 to 446 per 100,000 in 2010.

Cancer rates were higher among men (503 per 100,000) than women (405 per 100,000). In all, there were 745,383 cases reported among men and 711,113 among women in 2010.

The highest rates were for cancers of the prostate (126 per 100,000), female breast (119 per 100,000), lung and bronchus (62 per 100,000), and colon and rectum (40 per 100,000). Together, these accounted for half of all cancer cases in the US.

However, hematologic malignancies were fairly common as well. NHL was the 6th most common cancer for men of all races/ethnicities except Hispanic. For this group, NHL was the 4th most common cancer.

NHL was the 7th most common cancer for black and white women and 6th for the remaining groups, which included American Indian/Alaskan native, Asian/Pacific Islander, and Hispanic women.

Leukemia and myeloma were also among the top 10 most common invasive cancers for certain patients.

Leukemia was the 9th most common cancer for Hispanic and white men and the 10th for American Indian/Alaskan Native women. Myeloma was the 8th most common cancer for black women.

Overall, cancer rates were highest among black patients (455 per 100,000), followed by whites (445 per 100,000), Hispanics (344 per 100,000), Asian/Pacific Islanders (289 per 100,000), and American Indians/Alaskan Natives (270 per 100,000).

Nurse treating cancer patient

Credit: Rhoda Baer

A new report shows the rate of invasive cancer among US men and women dropped slightly from 2009 to 2010, and the most common cancers were solid tumor malignancies.

However, non-Hodgkin lymphoma (NHL) consistently rated among the top 10 most common cancers, regardless of patient gender or race.

The report was prepared by the Centers for Disease Control and Prevention (CDC) and appears in the current Morbidity and Mortality Weekly Report.

Researchers analyzed new cases of invasive cancers diagnosed in 2010 and reported to the CDC’s National Program of Cancer Registries and the National Cancer Institute’s Surveillance, Epidemiology and Results Program.

Data from all states (except Arkansas and Minnesota) and the District of Columbia were included in the analysis, which covered 97% of the US population.

The researchers found the rates of invasive cancer cases dropped from 459 per 100,000 people in 2009 to 446 per 100,000 in 2010.

Cancer rates were higher among men (503 per 100,000) than women (405 per 100,000). In all, there were 745,383 cases reported among men and 711,113 among women in 2010.

The highest rates were for cancers of the prostate (126 per 100,000), female breast (119 per 100,000), lung and bronchus (62 per 100,000), and colon and rectum (40 per 100,000). Together, these accounted for half of all cancer cases in the US.

However, hematologic malignancies were fairly common as well. NHL was the 6th most common cancer for men of all races/ethnicities except Hispanic. For this group, NHL was the 4th most common cancer.

NHL was the 7th most common cancer for black and white women and 6th for the remaining groups, which included American Indian/Alaskan native, Asian/Pacific Islander, and Hispanic women.

Leukemia and myeloma were also among the top 10 most common invasive cancers for certain patients.

Leukemia was the 9th most common cancer for Hispanic and white men and the 10th for American Indian/Alaskan Native women. Myeloma was the 8th most common cancer for black women.

Overall, cancer rates were highest among black patients (455 per 100,000), followed by whites (445 per 100,000), Hispanics (344 per 100,000), Asian/Pacific Islanders (289 per 100,000), and American Indians/Alaskan Natives (270 per 100,000).

Red blood cells

Credit: NHLBI

Results of preclinical research could aid the development of new treatments for hemolysis, which may have implications for patients with sickle cell anemia and those who receive blood transfusions.

The researchers were investigating the possibility of using haptoglobin to prevent the chemical reactions triggered by hemoglobin after hemolysis.

Haptoglobin is known to bind acellular adult hemoglobin dimers and facilitate their clearance after hemolysis.

But haptoglobin exists in different forms. The 3 main phenotypes—Hp1-1, Hp2-1, and Hp2-2—have diverse structural configurations, and previous research suggested they have different biological activities.

With the current study, however, the researchers showed the different forms of haptoglobin actually exhibit similar activity.

Todd L. Mollan, PhD, of the Center for Biologics Evaluation and Research at the Food and Drug Administration in Bethesda, Maryland, and his colleagues presented these findings in Free Radical Biology and Medicine.

The researchers studied hemoglobin dimers in complex with unfractionated haptoglobin (a mixture of Hp1-1, Hp2-1, and Hp2-2); fractionated, dimeric haptoglobin (Hp1-1); and fractionated, polymeric haptoglobin (predominantly Hp2-2, with minor amounts of Hp2-1).

The team also complexed ferrous and ferric hemoglobins with unfractionated haptoglobin and its fractionated forms.

Experiments revealed no significant differences among the different complexes with regard to hemoglobin-haptoglobin binding kinetics, hydrogen-peroxide-driven oxidative transitions of the heme iron, radical formation, heme loss, or intrinsic redox potential.

The researchers said these results should be taken into account when designing phenotype-specific haptoglobin therapies.

Red blood cells

Credit: NHLBI

Results of preclinical research could aid the development of new treatments for hemolysis, which may have implications for patients with sickle cell anemia and those who receive blood transfusions.

The researchers were investigating the possibility of using haptoglobin to prevent the chemical reactions triggered by hemoglobin after hemolysis.

Haptoglobin is known to bind acellular adult hemoglobin dimers and facilitate their clearance after hemolysis.

But haptoglobin exists in different forms. The 3 main phenotypes—Hp1-1, Hp2-1, and Hp2-2—have diverse structural configurations, and previous research suggested they have different biological activities.

With the current study, however, the researchers showed the different forms of haptoglobin actually exhibit similar activity.

Todd L. Mollan, PhD, of the Center for Biologics Evaluation and Research at the Food and Drug Administration in Bethesda, Maryland, and his colleagues presented these findings in Free Radical Biology and Medicine.

The researchers studied hemoglobin dimers in complex with unfractionated haptoglobin (a mixture of Hp1-1, Hp2-1, and Hp2-2); fractionated, dimeric haptoglobin (Hp1-1); and fractionated, polymeric haptoglobin (predominantly Hp2-2, with minor amounts of Hp2-1).

The team also complexed ferrous and ferric hemoglobins with unfractionated haptoglobin and its fractionated forms.

Experiments revealed no significant differences among the different complexes with regard to hemoglobin-haptoglobin binding kinetics, hydrogen-peroxide-driven oxidative transitions of the heme iron, radical formation, heme loss, or intrinsic redox potential.

The researchers said these results should be taken into account when designing phenotype-specific haptoglobin therapies.

Red blood cells

Credit: NHLBI

Results of preclinical research could aid the development of new treatments for hemolysis, which may have implications for patients with sickle cell anemia and those who receive blood transfusions.

The researchers were investigating the possibility of using haptoglobin to prevent the chemical reactions triggered by hemoglobin after hemolysis.

Haptoglobin is known to bind acellular adult hemoglobin dimers and facilitate their clearance after hemolysis.

But haptoglobin exists in different forms. The 3 main phenotypes—Hp1-1, Hp2-1, and Hp2-2—have diverse structural configurations, and previous research suggested they have different biological activities.

With the current study, however, the researchers showed the different forms of haptoglobin actually exhibit similar activity.

Todd L. Mollan, PhD, of the Center for Biologics Evaluation and Research at the Food and Drug Administration in Bethesda, Maryland, and his colleagues presented these findings in Free Radical Biology and Medicine.

The researchers studied hemoglobin dimers in complex with unfractionated haptoglobin (a mixture of Hp1-1, Hp2-1, and Hp2-2); fractionated, dimeric haptoglobin (Hp1-1); and fractionated, polymeric haptoglobin (predominantly Hp2-2, with minor amounts of Hp2-1).

The team also complexed ferrous and ferric hemoglobins with unfractionated haptoglobin and its fractionated forms.

Experiments revealed no significant differences among the different complexes with regard to hemoglobin-haptoglobin binding kinetics, hydrogen-peroxide-driven oxidative transitions of the heme iron, radical formation, heme loss, or intrinsic redox potential.

The researchers said these results should be taken into account when designing phenotype-specific haptoglobin therapies.

Monoclonal antibodies

Credit: Linda Bartlett

The UK’s National Institute for Health and Care Excellence (NICE) has published a final guidance recommending rituximab (MabThera) as a treatment option for adults with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis.

The guidance applies to adults with severe microscopic polyangiitis or granulomatosis with polyangiitis.

The guidance recommends rituximab in combination with glucocorticoids for certain patients in this population.

According to NICE, the treatment is suitable only if:

• The patient is in danger of exceeding the maximum amount of cyclophosphamide
• The patient cannot or should not receive cyclophosphamide
• Loss of fertility (due to cyclophosphamide) is a concern
• The patient’s disease did not respond to a course of cyclophosphamide lasting 3 to 6 months
• The patient has had uroepithelial cancer.

About ANCA-associated vasculitis

ANCA-associated vasculitis is an inflammatory autoimmune disease affecting the blood vessel walls. It can affect many organs and leads to tissue breakdown and damage. Granulomatosis with polyangiitis and microscopic polyangiitis are types of ANCA-associated vasculitis that affect small blood vessels.

ANCA-associated vasculitis usually affects the lungs, kidneys, ears, nose or sinuses. Depending on the organs involved, it can cause bleeding, rash, or deafness.

The aim of treatment is initially to induce remission, then to maintain remission and treat relapse when necessary. With adequate ongoing care, most patients with ANCA-associated vasculitis will have a good quality of life and normal life expectancy.

“The effects of vasculitis, as well as the stress of the fear of relapse, can often have a significant detrimental impact on patients’ quality of life,” said Carole Longson, PhD, Health Technology Evaluation Centre Director at NICE.

“The introduction of immunosuppressant therapy with cyclophosphamide and corticosteroids has dramatically improved the prognosis from a condition with high mortality to being a chronic disease with a relapsing and remitting course. However, these treatments are associated with substantial side effects that can further impair patients’ quality of life.”

Rituximab for ANCA-associated vasculitis

An independent advisory committee informed NICE that rituximab is a clinically effective and cost-effective option for some patients with severe microscopic polyangiitis or granulomatosis with polyangiitis.

“The committee heard that rituximab is the first effective treatment since the introduction of cyclophosphamide in the 1970s,” Dr Longson said. “In addition, they heard from the clinical specialists and patient experts that induction treatment with rituximab was 4 weeks instead of up to 6 months with cyclophosphamide, which was more convenient for patients.”

“The committee concluded that rituximab is an innovative treatment for vasculitis and that this benefit is important to patients. The committee also concluded that rituximab is a cost-effective use of NHS resources for those groups specified in the guidance.”

Rituximab is priced at £174.63 per 10 mL vial and £873.15 per 50 mL vial (excluding tax). The manufacturer’s estimate of the average cost of a course of treatment is £4889.64 (based on 1.79 m² body surface area and no vial sharing). Costs may vary in different settings because of negotiated procurement discounts.

Monoclonal antibodies

Credit: Linda Bartlett

The UK’s National Institute for Health and Care Excellence (NICE) has published a final guidance recommending rituximab (MabThera) as a treatment option for adults with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis.

The guidance applies to adults with severe microscopic polyangiitis or granulomatosis with polyangiitis.

The guidance recommends rituximab in combination with glucocorticoids for certain patients in this population.

According to NICE, the treatment is suitable only if:

• The patient is in danger of exceeding the maximum amount of cyclophosphamide
• The patient cannot or should not receive cyclophosphamide
• Loss of fertility (due to cyclophosphamide) is a concern
• The patient’s disease did not respond to a course of cyclophosphamide lasting 3 to 6 months
• The patient has had uroepithelial cancer.

About ANCA-associated vasculitis

ANCA-associated vasculitis is an inflammatory autoimmune disease affecting the blood vessel walls. It can affect many organs and leads to tissue breakdown and damage. Granulomatosis with polyangiitis and microscopic polyangiitis are types of ANCA-associated vasculitis that affect small blood vessels.

ANCA-associated vasculitis usually affects the lungs, kidneys, ears, nose or sinuses. Depending on the organs involved, it can cause bleeding, rash, or deafness.

The aim of treatment is initially to induce remission, then to maintain remission and treat relapse when necessary. With adequate ongoing care, most patients with ANCA-associated vasculitis will have a good quality of life and normal life expectancy.

“The effects of vasculitis, as well as the stress of the fear of relapse, can often have a significant detrimental impact on patients’ quality of life,” said Carole Longson, PhD, Health Technology Evaluation Centre Director at NICE.

“The introduction of immunosuppressant therapy with cyclophosphamide and corticosteroids has dramatically improved the prognosis from a condition with high mortality to being a chronic disease with a relapsing and remitting course. However, these treatments are associated with substantial side effects that can further impair patients’ quality of life.”

Rituximab for ANCA-associated vasculitis

An independent advisory committee informed NICE that rituximab is a clinically effective and cost-effective option for some patients with severe microscopic polyangiitis or granulomatosis with polyangiitis.

“The committee heard that rituximab is the first effective treatment since the introduction of cyclophosphamide in the 1970s,” Dr Longson said. “In addition, they heard from the clinical specialists and patient experts that induction treatment with rituximab was 4 weeks instead of up to 6 months with cyclophosphamide, which was more convenient for patients.”

“The committee concluded that rituximab is an innovative treatment for vasculitis and that this benefit is important to patients. The committee also concluded that rituximab is a cost-effective use of NHS resources for those groups specified in the guidance.”

Rituximab is priced at £174.63 per 10 mL vial and £873.15 per 50 mL vial (excluding tax). The manufacturer’s estimate of the average cost of a course of treatment is £4889.64 (based on 1.79 m² body surface area and no vial sharing). Costs may vary in different settings because of negotiated procurement discounts.

Monoclonal antibodies

Credit: Linda Bartlett

The UK’s National Institute for Health and Care Excellence (NICE) has published a final guidance recommending rituximab (MabThera) as a treatment option for adults with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis.

The guidance applies to adults with severe microscopic polyangiitis or granulomatosis with polyangiitis.

The guidance recommends rituximab in combination with glucocorticoids for certain patients in this population.

According to NICE, the treatment is suitable only if:

• The patient is in danger of exceeding the maximum amount of cyclophosphamide
• The patient cannot or should not receive cyclophosphamide
• Loss of fertility (due to cyclophosphamide) is a concern
• The patient’s disease did not respond to a course of cyclophosphamide lasting 3 to 6 months
• The patient has had uroepithelial cancer.

About ANCA-associated vasculitis

ANCA-associated vasculitis is an inflammatory autoimmune disease affecting the blood vessel walls. It can affect many organs and leads to tissue breakdown and damage. Granulomatosis with polyangiitis and microscopic polyangiitis are types of ANCA-associated vasculitis that affect small blood vessels.

ANCA-associated vasculitis usually affects the lungs, kidneys, ears, nose or sinuses. Depending on the organs involved, it can cause bleeding, rash, or deafness.

The aim of treatment is initially to induce remission, then to maintain remission and treat relapse when necessary. With adequate ongoing care, most patients with ANCA-associated vasculitis will have a good quality of life and normal life expectancy.

“The effects of vasculitis, as well as the stress of the fear of relapse, can often have a significant detrimental impact on patients’ quality of life,” said Carole Longson, PhD, Health Technology Evaluation Centre Director at NICE.

“The introduction of immunosuppressant therapy with cyclophosphamide and corticosteroids has dramatically improved the prognosis from a condition with high mortality to being a chronic disease with a relapsing and remitting course. However, these treatments are associated with substantial side effects that can further impair patients’ quality of life.”

Rituximab for ANCA-associated vasculitis

An independent advisory committee informed NICE that rituximab is a clinically effective and cost-effective option for some patients with severe microscopic polyangiitis or granulomatosis with polyangiitis.

“The committee heard that rituximab is the first effective treatment since the introduction of cyclophosphamide in the 1970s,” Dr Longson said. “In addition, they heard from the clinical specialists and patient experts that induction treatment with rituximab was 4 weeks instead of up to 6 months with cyclophosphamide, which was more convenient for patients.”

“The committee concluded that rituximab is an innovative treatment for vasculitis and that this benefit is important to patients. The committee also concluded that rituximab is a cost-effective use of NHS resources for those groups specified in the guidance.”

Rituximab is priced at £174.63 per 10 mL vial and £873.15 per 50 mL vial (excluding tax). The manufacturer’s estimate of the average cost of a course of treatment is £4889.64 (based on 1.79 m² body surface area and no vial sharing). Costs may vary in different settings because of negotiated procurement discounts.

Zebrafish embryos

Research in zebrafish embryos may help explain the link between Max’s giant-associated protein (MGA) and Richter’s syndrome.

Previous studies showed that mutations in MGA are associated with a high risk of Richter’s syndrome, a rare lymphoma that can occur in patients with chronic lymphocytic leukemia.

Now, a team of biologists has discovered how MGA controls developmental processes. They described their discoveries in Developmental Cell.

“The same genes that are involved in building a person during embryonic development can mutate and cause cancer later in life,” said study author Scott Dougan, PhD, of the University of Georgia in Athens.

“No one has done a systematic study of MGA, but now that some studies connect it to cancer, there is tremendous interest.”

Preliminary tests have suggested that Richter’s syndrome might develop when MGA does not successfully control the activities of the MYC oncogene.

Dr Dougan and his colleagues decided to alter the levels of MGA in zebrafish embryos to see if they could discover any other roles for MGA.

They found that MGA also helps control the expression of bone morphogenetic proteins (BMPs). Specifically, a transcription factor complex consisting of MGA, Max, and Smad4 controls the expression of bmp2b/swirl in the zebrafish yolk syncytial layer. And this controls BMP signaling throughout the embryo.

BMPs are responsible for bone development in the embryo, but, in adults, changes in BMP activity can result in tumor development. This research suggests MGA may be part of this transformation.

“Scientists are only beginning to understand the roles this MGA protein plays, but our tests show that MGA may control many more processes than first imagined,” Dr Dougan said. “MGA may be involved in a number of other cancers, but we need to do more research before we’re sure.”

In the coming months, Dr Dougan and his colleagues plan to further examine the roles of MGA to determine when it controls MYC, when it controls BMP, and how it is involved in tumor formation.

“[W]e need investigations like these to understand the fundamentals of our biology,” Dr Dougan said. “Once we have this understanding, we can begin to develop new therapies to treat diseases in new, more effective ways.”

Zebrafish embryos

Research in zebrafish embryos may help explain the link between Max’s giant-associated protein (MGA) and Richter’s syndrome.

Previous studies showed that mutations in MGA are associated with a high risk of Richter’s syndrome, a rare lymphoma that can occur in patients with chronic lymphocytic leukemia.

Now, a team of biologists has discovered how MGA controls developmental processes. They described their discoveries in Developmental Cell.

“The same genes that are involved in building a person during embryonic development can mutate and cause cancer later in life,” said study author Scott Dougan, PhD, of the University of Georgia in Athens.

“No one has done a systematic study of MGA, but now that some studies connect it to cancer, there is tremendous interest.”

Preliminary tests have suggested that Richter’s syndrome might develop when MGA does not successfully control the activities of the MYC oncogene.

Dr Dougan and his colleagues decided to alter the levels of MGA in zebrafish embryos to see if they could discover any other roles for MGA.

They found that MGA also helps control the expression of bone morphogenetic proteins (BMPs). Specifically, a transcription factor complex consisting of MGA, Max, and Smad4 controls the expression of bmp2b/swirl in the zebrafish yolk syncytial layer. And this controls BMP signaling throughout the embryo.

BMPs are responsible for bone development in the embryo, but, in adults, changes in BMP activity can result in tumor development. This research suggests MGA may be part of this transformation.

“Scientists are only beginning to understand the roles this MGA protein plays, but our tests show that MGA may control many more processes than first imagined,” Dr Dougan said. “MGA may be involved in a number of other cancers, but we need to do more research before we’re sure.”

In the coming months, Dr Dougan and his colleagues plan to further examine the roles of MGA to determine when it controls MYC, when it controls BMP, and how it is involved in tumor formation.

“[W]e need investigations like these to understand the fundamentals of our biology,” Dr Dougan said. “Once we have this understanding, we can begin to develop new therapies to treat diseases in new, more effective ways.”

Zebrafish embryos

Research in zebrafish embryos may help explain the link between Max’s giant-associated protein (MGA) and Richter’s syndrome.

Previous studies showed that mutations in MGA are associated with a high risk of Richter’s syndrome, a rare lymphoma that can occur in patients with chronic lymphocytic leukemia.

Now, a team of biologists has discovered how MGA controls developmental processes. They described their discoveries in Developmental Cell.

“The same genes that are involved in building a person during embryonic development can mutate and cause cancer later in life,” said study author Scott Dougan, PhD, of the University of Georgia in Athens.

“No one has done a systematic study of MGA, but now that some studies connect it to cancer, there is tremendous interest.”

Preliminary tests have suggested that Richter’s syndrome might develop when MGA does not successfully control the activities of the MYC oncogene.

Dr Dougan and his colleagues decided to alter the levels of MGA in zebrafish embryos to see if they could discover any other roles for MGA.

They found that MGA also helps control the expression of bone morphogenetic proteins (BMPs). Specifically, a transcription factor complex consisting of MGA, Max, and Smad4 controls the expression of bmp2b/swirl in the zebrafish yolk syncytial layer. And this controls BMP signaling throughout the embryo.

BMPs are responsible for bone development in the embryo, but, in adults, changes in BMP activity can result in tumor development. This research suggests MGA may be part of this transformation.

“Scientists are only beginning to understand the roles this MGA protein plays, but our tests show that MGA may control many more processes than first imagined,” Dr Dougan said. “MGA may be involved in a number of other cancers, but we need to do more research before we’re sure.”

In the coming months, Dr Dougan and his colleagues plan to further examine the roles of MGA to determine when it controls MYC, when it controls BMP, and how it is involved in tumor formation.

“[W]e need investigations like these to understand the fundamentals of our biology,” Dr Dougan said. “Once we have this understanding, we can begin to develop new therapies to treat diseases in new, more effective ways.”