Leukemia, Myelodysplasia, Transplantation

Photo courtesy of the CDC

A study of residents in Ontario, Canada, showed that opioid prescription use was more common in cancer survivors than in individuals without a history of cancer.

This was true even among survivors who were 10 or more years past their cancer diagnosis.

Rinku Sutradhar, PhD, of the University of Toronto in Ontario, Canada, and her colleagues reported these findings in Cancer.

The researchers said little is known about prescribing opioids to relieve pain in individuals who have survived cancer.

To investigate, the team looked at opioid prescribing among residents of Ontario, Canada, with and without a history of cancer.

The study included 8601 adults who were at least 5 years past a cancer diagnosis. These subjects were were matched with 8601 individuals without a prior cancer diagnosis. The subjects were matched based on sex and calendar year of birth.

The researchers looked for opioid prescriptions filled at a pharmacy during the observation period. Follow-up was stopped at any indication of cancer recurrence, second malignancy, or new cancer diagnosis.

The rate of opioid prescribing was 1.22 times higher among cancer survivors than corresponding matched controls.

Over a 36-month period, the average number of opioid prescriptions filled by cancer survivors was 7.7, compared with 6.3 for controls.

This increased rate of opioid prescribing was also seen among survivors who were 10 or more years past their cancer diagnosis.

Individuals with lower income and those who were younger, from rural neighborhoods, and with more comorbidities had significantly higher prescribing rates. Sex was not associated with prescribing rates.

“Our research findings raise concerns about the diagnosis and management of chronic pain problems among survivors stemming from their cancer diagnosis or treatment,” Dr Sutradhar said. “Physicians providing primary care to cancer survivors should consider close examination of reasons for continued opioid use to differentiate chronic pain from dependency.”

Photo courtesy of the CDC

A study of residents in Ontario, Canada, showed that opioid prescription use was more common in cancer survivors than in individuals without a history of cancer.

This was true even among survivors who were 10 or more years past their cancer diagnosis.

Rinku Sutradhar, PhD, of the University of Toronto in Ontario, Canada, and her colleagues reported these findings in Cancer.

The researchers said little is known about prescribing opioids to relieve pain in individuals who have survived cancer.

To investigate, the team looked at opioid prescribing among residents of Ontario, Canada, with and without a history of cancer.

The study included 8601 adults who were at least 5 years past a cancer diagnosis. These subjects were were matched with 8601 individuals without a prior cancer diagnosis. The subjects were matched based on sex and calendar year of birth.

The researchers looked for opioid prescriptions filled at a pharmacy during the observation period. Follow-up was stopped at any indication of cancer recurrence, second malignancy, or new cancer diagnosis.

The rate of opioid prescribing was 1.22 times higher among cancer survivors than corresponding matched controls.

Over a 36-month period, the average number of opioid prescriptions filled by cancer survivors was 7.7, compared with 6.3 for controls.

This increased rate of opioid prescribing was also seen among survivors who were 10 or more years past their cancer diagnosis.

Individuals with lower income and those who were younger, from rural neighborhoods, and with more comorbidities had significantly higher prescribing rates. Sex was not associated with prescribing rates.

“Our research findings raise concerns about the diagnosis and management of chronic pain problems among survivors stemming from their cancer diagnosis or treatment,” Dr Sutradhar said. “Physicians providing primary care to cancer survivors should consider close examination of reasons for continued opioid use to differentiate chronic pain from dependency.”

Photo courtesy of the CDC

A study of residents in Ontario, Canada, showed that opioid prescription use was more common in cancer survivors than in individuals without a history of cancer.

This was true even among survivors who were 10 or more years past their cancer diagnosis.

Rinku Sutradhar, PhD, of the University of Toronto in Ontario, Canada, and her colleagues reported these findings in Cancer.

The researchers said little is known about prescribing opioids to relieve pain in individuals who have survived cancer.

To investigate, the team looked at opioid prescribing among residents of Ontario, Canada, with and without a history of cancer.

The study included 8601 adults who were at least 5 years past a cancer diagnosis. These subjects were were matched with 8601 individuals without a prior cancer diagnosis. The subjects were matched based on sex and calendar year of birth.

The researchers looked for opioid prescriptions filled at a pharmacy during the observation period. Follow-up was stopped at any indication of cancer recurrence, second malignancy, or new cancer diagnosis.

The rate of opioid prescribing was 1.22 times higher among cancer survivors than corresponding matched controls.

Over a 36-month period, the average number of opioid prescriptions filled by cancer survivors was 7.7, compared with 6.3 for controls.

This increased rate of opioid prescribing was also seen among survivors who were 10 or more years past their cancer diagnosis.

Individuals with lower income and those who were younger, from rural neighborhoods, and with more comorbidities had significantly higher prescribing rates. Sex was not associated with prescribing rates.

“Our research findings raise concerns about the diagnosis and management of chronic pain problems among survivors stemming from their cancer diagnosis or treatment,” Dr Sutradhar said. “Physicians providing primary care to cancer survivors should consider close examination of reasons for continued opioid use to differentiate chronic pain from dependency.”

Photo by Rhoda Baer

A study of 300 US cancer patients showed that paying for care can cause “overwhelming” financial distress, even when patients have health insurance.

Sixteen percent of the patients studied reported “high or overwhelming” financial distress, spending a median of 31% of their monthly household income on healthcare, not including insurance premiums.

They had a median monthly out-of-pocket cost of $728 (range, $6 to $47,250).

Fumiko Chino, MD, of Duke University Medical Center in Durham, North Carolina, and her colleagues reported these findings in a letter to JAMA Oncology.

The researchers interviewed 300 insured cancer patients for this study. They had a median age of 59.6, and 68.3% were married.

Fifty-six percent of patients had private insurance, 35.7% had Medicare, and 7.3% had Medicaid.

Annual household incomes were as follows:

• 45.7%, $60,000 or greater
• 15.7%, $40,000 to $59,999
• 17.7%, $20,000 to 39,999
• 13.7%, lower than $20,000
• 7.3%, unknown.

The median monthly out-of-pocket cost for care was $592 (range, $3-$47,250), not including insurance premiums. The median relative cost of care was 11% of a patient’s monthly household income.

“Those who spend more than 10% of their income on healthcare costs are considered underinsured,” Dr Chino said. “Learning about the cost-sharing burden on some insured patients is important right now, given the uncertainty in health insurance.”

Most of the patients studied (83.7%, n=251) reported no, low, or average financial distress. Their median relative cost of care was 10% of their monthly household income, and their median monthly out-of-pocket cost was $565 (range, $3 to $26,756). Six percent of these patients had Medicaid, 39% had Medicare, and 53.8% had private insurance.

For the 16.3% of patients (n=49) who reported high or overwhelming financial distress, 67.3% had private insurance, 18.4% had Medicare, and 14.3% had Medicaid. As stated above, their median relative cost of care was 31% of their monthly household income, and their median monthly out-of-pocket cost was $728 (range, $6 to $47,250).

“This study adds to the growing evidence that we need to intervene,” said study author Yousuf Zafar, MD, of Duke Cancer Institute.

“We know there are a lot of barriers that prevent patients from talking about cost with their providers. We need to create tools for patients at risk of financial toxicity and connect them with resources in a timely fashion so they can afford their care.”

Photo by Rhoda Baer

A study of 300 US cancer patients showed that paying for care can cause “overwhelming” financial distress, even when patients have health insurance.

Sixteen percent of the patients studied reported “high or overwhelming” financial distress, spending a median of 31% of their monthly household income on healthcare, not including insurance premiums.

They had a median monthly out-of-pocket cost of $728 (range, $6 to $47,250).

Fumiko Chino, MD, of Duke University Medical Center in Durham, North Carolina, and her colleagues reported these findings in a letter to JAMA Oncology.

The researchers interviewed 300 insured cancer patients for this study. They had a median age of 59.6, and 68.3% were married.

Fifty-six percent of patients had private insurance, 35.7% had Medicare, and 7.3% had Medicaid.

Annual household incomes were as follows:

• 45.7%, $60,000 or greater
• 15.7%, $40,000 to $59,999
• 17.7%, $20,000 to 39,999
• 13.7%, lower than $20,000
• 7.3%, unknown.

The median monthly out-of-pocket cost for care was $592 (range, $3-$47,250), not including insurance premiums. The median relative cost of care was 11% of a patient’s monthly household income.

“Those who spend more than 10% of their income on healthcare costs are considered underinsured,” Dr Chino said. “Learning about the cost-sharing burden on some insured patients is important right now, given the uncertainty in health insurance.”

Most of the patients studied (83.7%, n=251) reported no, low, or average financial distress. Their median relative cost of care was 10% of their monthly household income, and their median monthly out-of-pocket cost was $565 (range, $3 to $26,756). Six percent of these patients had Medicaid, 39% had Medicare, and 53.8% had private insurance.

For the 16.3% of patients (n=49) who reported high or overwhelming financial distress, 67.3% had private insurance, 18.4% had Medicare, and 14.3% had Medicaid. As stated above, their median relative cost of care was 31% of their monthly household income, and their median monthly out-of-pocket cost was $728 (range, $6 to $47,250).

“This study adds to the growing evidence that we need to intervene,” said study author Yousuf Zafar, MD, of Duke Cancer Institute.

“We know there are a lot of barriers that prevent patients from talking about cost with their providers. We need to create tools for patients at risk of financial toxicity and connect them with resources in a timely fashion so they can afford their care.”

Photo by Rhoda Baer

A study of 300 US cancer patients showed that paying for care can cause “overwhelming” financial distress, even when patients have health insurance.

Sixteen percent of the patients studied reported “high or overwhelming” financial distress, spending a median of 31% of their monthly household income on healthcare, not including insurance premiums.

They had a median monthly out-of-pocket cost of $728 (range, $6 to $47,250).

Fumiko Chino, MD, of Duke University Medical Center in Durham, North Carolina, and her colleagues reported these findings in a letter to JAMA Oncology.

The researchers interviewed 300 insured cancer patients for this study. They had a median age of 59.6, and 68.3% were married.

Fifty-six percent of patients had private insurance, 35.7% had Medicare, and 7.3% had Medicaid.

Annual household incomes were as follows:

• 45.7%, $60,000 or greater
• 15.7%, $40,000 to $59,999
• 17.7%, $20,000 to 39,999
• 13.7%, lower than $20,000
• 7.3%, unknown.

The median monthly out-of-pocket cost for care was $592 (range, $3-$47,250), not including insurance premiums. The median relative cost of care was 11% of a patient’s monthly household income.

“Those who spend more than 10% of their income on healthcare costs are considered underinsured,” Dr Chino said. “Learning about the cost-sharing burden on some insured patients is important right now, given the uncertainty in health insurance.”

Most of the patients studied (83.7%, n=251) reported no, low, or average financial distress. Their median relative cost of care was 10% of their monthly household income, and their median monthly out-of-pocket cost was $565 (range, $3 to $26,756). Six percent of these patients had Medicaid, 39% had Medicare, and 53.8% had private insurance.

For the 16.3% of patients (n=49) who reported high or overwhelming financial distress, 67.3% had private insurance, 18.4% had Medicare, and 14.3% had Medicaid. As stated above, their median relative cost of care was 31% of their monthly household income, and their median monthly out-of-pocket cost was $728 (range, $6 to $47,250).

“This study adds to the growing evidence that we need to intervene,” said study author Yousuf Zafar, MD, of Duke Cancer Institute.

“We know there are a lot of barriers that prevent patients from talking about cost with their providers. We need to create tools for patients at risk of financial toxicity and connect them with resources in a timely fashion so they can afford their care.”

Lab mouse

Researchers believe they may have found a way to prevent chemotherapy-induced myelosuppression in acute myeloid leukemia (AML).

The team found that priming mice with the FLT3 inhibitor quizartinib protected multipotent progenitor cells (MPPs) from subsequent treatment with fluorouracil (5-FU) or gemcitabine.

And treatment with quizartinib followed by 5-FU proved more effective against AML than standard induction with cytarabine and doxorubicin.

Samuel Taylor, of the University of Western Australia in Crawley, Australia, and his colleagues reported these results in Science Translational Medicine.

The researchers first found that quizartinib induced “rapid and transient” quiescence of MPPs in C57BL/6 mice.

Quizartinib also provided MPPs with “marked protection” from 5-FU. In these experiments, a 10 mg/kg dose of quizartinib was given to mice at the same time as a 150 mg/kg dose of 5-FU. This treatment provided MPPs with 4- to 5-fold greater protection than vehicle control.

Subsequent experiments revealed the optimal dose and schedule for quizartinib. A priming dose of 30 mg/kg given 6 hours before 5-FU provided “slightly greater” protection to hematopoietic stem and progenitor cells than a 10 mg/kg dose, with significantly greater protection observed for short-term hematopoietic stem cells.

The researchers then showed that priming with quizartinib allowed for “rapid recovery of bone marrow cellularity” after treatment with 5-FU. Bone marrow cells were fully restored by day 8 after treatment in quizartinib-primed mice but not in vehicle-primed mice.

Quizartinib priming also protected mice from multiple rounds of treatment with 5-FU (15 cycles in some mice) and from myelosuppression induced by gemcitabine.

Finally, the researchers tested quizartinib followed by 5-FU in mouse models of AML. They found the treatment was more effective than treatment with cytarabine and doxorubicin in both FLT3-ITD(F692L)/NPM1c AML and NPM1c/Nras^G12D AML.

FLT3-ITD(F692L)/NPM1c AML

The researchers transplanted 15 non-irradiated B6.CD45.1 mice with 3 × 10⁵ spleen cells each from a FLT3-ITD(F691L)/NPM1c mouse that succumbed to AML at 6 weeks of age. Sixteen days after transplant, the mice were given one of the following:

• No treatment
• 10-day cycles of quizartinib (30 mg/kg) followed 6 hours later by 5-FU (150 mg/kg)
• Cytarabine plus doxorubicin (5+3).

All 5 of the untreated mice died within 30 days of transplantation, exhibiting high white blood cell (WBC) counts and splenomegaly.

The 5+3 mice received 2 cycles of treatment (days 16 to 21 and 36 to 41). All 5 had died by day 56 after transplantation, with high WBC counts and splenomegaly.

One the other hand, 4 of the 5 mice in the quizartinib/5-FU arm were still healthy at 176 days after transplantation and 80 days after stopping treatment. There were no detectable CD45.2+ AML cells when the mice were last bled on day 160, and they had normal WBC counts. There were no AML cells detectable in the animals’ bone marrow after they were killed at day 176.

The quizartinib/5-FU mouse that died before day 176 is believed to have developed resistance to 5-FU. This animal died 121 days after transplantation.

NPM1c/ Nras^G12D AML

For another AML model, the researchers crossed NPM1c-mutant mice with Nras^G12D-mutant mice. The team transplanted spleen cells from NPM1c/Nras^G12D leukemic mice into 15 non-irradiated B6.CD45.1 recipient mice.

Fifteen days after transplantation, the NPM1c/ Nras^G12D mice received one of the following:

• No treatment
• Quizartinib and 5-FU as above
• Cytarabine plus doxorubicin (5+3).

All 5 untreated mice died by day 32 after transplantation, and all 5 mice that received 5+3 died by day 35. Both groups of mice had high WBC counts and splenomegaly.

Mice in the quizartinib/5-FU arm initially received 4 cycles of treatment, starting on days 15, 25, 35, and 45 after transplantation. On day 53, they had minimal or undetectable numbers of CD45.2+ AML cells, and WBC counts were normal or slightly below normal.

At day 81—a month after stopping treatment—4 of the mice had detectable CD45.2+ AML cells in their blood. So they restarted treatment the next day. After 4 additional cycles, AML cells were undetectable in all 5 mice. At day 146—a month after stopping the second round of treatment—AML cells again became detectable in the blood.

The mice did not receive any additional treatment. One died at day 196, and 1 was killed at day 197 due to weight loss related to feeding difficulties (but this mouse did not show signs of AML).

The other 3 mice were “active and healthy” until they were killed at day 214. However, they had “high proportions” of CD45.2+ myeloid cells in their blood since day 183. And 2 of the mice had increased WBC counts from day 197.

Lab mouse

Researchers believe they may have found a way to prevent chemotherapy-induced myelosuppression in acute myeloid leukemia (AML).

The team found that priming mice with the FLT3 inhibitor quizartinib protected multipotent progenitor cells (MPPs) from subsequent treatment with fluorouracil (5-FU) or gemcitabine.

And treatment with quizartinib followed by 5-FU proved more effective against AML than standard induction with cytarabine and doxorubicin.

Samuel Taylor, of the University of Western Australia in Crawley, Australia, and his colleagues reported these results in Science Translational Medicine.

The researchers first found that quizartinib induced “rapid and transient” quiescence of MPPs in C57BL/6 mice.

Quizartinib also provided MPPs with “marked protection” from 5-FU. In these experiments, a 10 mg/kg dose of quizartinib was given to mice at the same time as a 150 mg/kg dose of 5-FU. This treatment provided MPPs with 4- to 5-fold greater protection than vehicle control.

Subsequent experiments revealed the optimal dose and schedule for quizartinib. A priming dose of 30 mg/kg given 6 hours before 5-FU provided “slightly greater” protection to hematopoietic stem and progenitor cells than a 10 mg/kg dose, with significantly greater protection observed for short-term hematopoietic stem cells.

The researchers then showed that priming with quizartinib allowed for “rapid recovery of bone marrow cellularity” after treatment with 5-FU. Bone marrow cells were fully restored by day 8 after treatment in quizartinib-primed mice but not in vehicle-primed mice.

Quizartinib priming also protected mice from multiple rounds of treatment with 5-FU (15 cycles in some mice) and from myelosuppression induced by gemcitabine.

Finally, the researchers tested quizartinib followed by 5-FU in mouse models of AML. They found the treatment was more effective than treatment with cytarabine and doxorubicin in both FLT3-ITD(F692L)/NPM1c AML and NPM1c/Nras^G12D AML.

FLT3-ITD(F692L)/NPM1c AML

The researchers transplanted 15 non-irradiated B6.CD45.1 mice with 3 × 10⁵ spleen cells each from a FLT3-ITD(F691L)/NPM1c mouse that succumbed to AML at 6 weeks of age. Sixteen days after transplant, the mice were given one of the following:

• No treatment
• 10-day cycles of quizartinib (30 mg/kg) followed 6 hours later by 5-FU (150 mg/kg)
• Cytarabine plus doxorubicin (5+3).

All 5 of the untreated mice died within 30 days of transplantation, exhibiting high white blood cell (WBC) counts and splenomegaly.

The 5+3 mice received 2 cycles of treatment (days 16 to 21 and 36 to 41). All 5 had died by day 56 after transplantation, with high WBC counts and splenomegaly.

One the other hand, 4 of the 5 mice in the quizartinib/5-FU arm were still healthy at 176 days after transplantation and 80 days after stopping treatment. There were no detectable CD45.2+ AML cells when the mice were last bled on day 160, and they had normal WBC counts. There were no AML cells detectable in the animals’ bone marrow after they were killed at day 176.

The quizartinib/5-FU mouse that died before day 176 is believed to have developed resistance to 5-FU. This animal died 121 days after transplantation.

NPM1c/ Nras^G12D AML

For another AML model, the researchers crossed NPM1c-mutant mice with Nras^G12D-mutant mice. The team transplanted spleen cells from NPM1c/Nras^G12D leukemic mice into 15 non-irradiated B6.CD45.1 recipient mice.

Fifteen days after transplantation, the NPM1c/ Nras^G12D mice received one of the following:

• No treatment
• Quizartinib and 5-FU as above
• Cytarabine plus doxorubicin (5+3).

All 5 untreated mice died by day 32 after transplantation, and all 5 mice that received 5+3 died by day 35. Both groups of mice had high WBC counts and splenomegaly.

Mice in the quizartinib/5-FU arm initially received 4 cycles of treatment, starting on days 15, 25, 35, and 45 after transplantation. On day 53, they had minimal or undetectable numbers of CD45.2+ AML cells, and WBC counts were normal or slightly below normal.

At day 81—a month after stopping treatment—4 of the mice had detectable CD45.2+ AML cells in their blood. So they restarted treatment the next day. After 4 additional cycles, AML cells were undetectable in all 5 mice. At day 146—a month after stopping the second round of treatment—AML cells again became detectable in the blood.

The mice did not receive any additional treatment. One died at day 196, and 1 was killed at day 197 due to weight loss related to feeding difficulties (but this mouse did not show signs of AML).

The other 3 mice were “active and healthy” until they were killed at day 214. However, they had “high proportions” of CD45.2+ myeloid cells in their blood since day 183. And 2 of the mice had increased WBC counts from day 197.

Lab mouse

Researchers believe they may have found a way to prevent chemotherapy-induced myelosuppression in acute myeloid leukemia (AML).

The team found that priming mice with the FLT3 inhibitor quizartinib protected multipotent progenitor cells (MPPs) from subsequent treatment with fluorouracil (5-FU) or gemcitabine.

And treatment with quizartinib followed by 5-FU proved more effective against AML than standard induction with cytarabine and doxorubicin.

Samuel Taylor, of the University of Western Australia in Crawley, Australia, and his colleagues reported these results in Science Translational Medicine.

The researchers first found that quizartinib induced “rapid and transient” quiescence of MPPs in C57BL/6 mice.

Quizartinib also provided MPPs with “marked protection” from 5-FU. In these experiments, a 10 mg/kg dose of quizartinib was given to mice at the same time as a 150 mg/kg dose of 5-FU. This treatment provided MPPs with 4- to 5-fold greater protection than vehicle control.

Subsequent experiments revealed the optimal dose and schedule for quizartinib. A priming dose of 30 mg/kg given 6 hours before 5-FU provided “slightly greater” protection to hematopoietic stem and progenitor cells than a 10 mg/kg dose, with significantly greater protection observed for short-term hematopoietic stem cells.

The researchers then showed that priming with quizartinib allowed for “rapid recovery of bone marrow cellularity” after treatment with 5-FU. Bone marrow cells were fully restored by day 8 after treatment in quizartinib-primed mice but not in vehicle-primed mice.

Quizartinib priming also protected mice from multiple rounds of treatment with 5-FU (15 cycles in some mice) and from myelosuppression induced by gemcitabine.

Finally, the researchers tested quizartinib followed by 5-FU in mouse models of AML. They found the treatment was more effective than treatment with cytarabine and doxorubicin in both FLT3-ITD(F692L)/NPM1c AML and NPM1c/Nras^G12D AML.

FLT3-ITD(F692L)/NPM1c AML

The researchers transplanted 15 non-irradiated B6.CD45.1 mice with 3 × 10⁵ spleen cells each from a FLT3-ITD(F691L)/NPM1c mouse that succumbed to AML at 6 weeks of age. Sixteen days after transplant, the mice were given one of the following:

• No treatment
• 10-day cycles of quizartinib (30 mg/kg) followed 6 hours later by 5-FU (150 mg/kg)
• Cytarabine plus doxorubicin (5+3).

All 5 of the untreated mice died within 30 days of transplantation, exhibiting high white blood cell (WBC) counts and splenomegaly.

The 5+3 mice received 2 cycles of treatment (days 16 to 21 and 36 to 41). All 5 had died by day 56 after transplantation, with high WBC counts and splenomegaly.

One the other hand, 4 of the 5 mice in the quizartinib/5-FU arm were still healthy at 176 days after transplantation and 80 days after stopping treatment. There were no detectable CD45.2+ AML cells when the mice were last bled on day 160, and they had normal WBC counts. There were no AML cells detectable in the animals’ bone marrow after they were killed at day 176.

The quizartinib/5-FU mouse that died before day 176 is believed to have developed resistance to 5-FU. This animal died 121 days after transplantation.

NPM1c/ Nras^G12D AML

For another AML model, the researchers crossed NPM1c-mutant mice with Nras^G12D-mutant mice. The team transplanted spleen cells from NPM1c/Nras^G12D leukemic mice into 15 non-irradiated B6.CD45.1 recipient mice.

Fifteen days after transplantation, the NPM1c/ Nras^G12D mice received one of the following:

• No treatment
• Quizartinib and 5-FU as above
• Cytarabine plus doxorubicin (5+3).

All 5 untreated mice died by day 32 after transplantation, and all 5 mice that received 5+3 died by day 35. Both groups of mice had high WBC counts and splenomegaly.

Mice in the quizartinib/5-FU arm initially received 4 cycles of treatment, starting on days 15, 25, 35, and 45 after transplantation. On day 53, they had minimal or undetectable numbers of CD45.2+ AML cells, and WBC counts were normal or slightly below normal.

At day 81—a month after stopping treatment—4 of the mice had detectable CD45.2+ AML cells in their blood. So they restarted treatment the next day. After 4 additional cycles, AML cells were undetectable in all 5 mice. At day 146—a month after stopping the second round of treatment—AML cells again became detectable in the blood.

The mice did not receive any additional treatment. One died at day 196, and 1 was killed at day 197 due to weight loss related to feeding difficulties (but this mouse did not show signs of AML).

The other 3 mice were “active and healthy” until they were killed at day 214. However, they had “high proportions” of CD45.2+ myeloid cells in their blood since day 183. And 2 of the mice had increased WBC counts from day 197.

Henrique Orlandi Mourao

Researchers have found evidence to suggest that a type of acute myeloid leukemia (AML) depends on the production of heme.

The group’s work has revealed 2 ways to target heme synthesis that might be used to treat this type of AML, which is driven by the oncogene MYCN.

John Schuetz, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee, and his colleague described this research in JCI Insight.

Previous research had suggested that heme production was affected in leukemia.

However, Dr Schuetz said, “Absolutely nothing was known about the role of heme biosynthesis [in AML] before our work.”

The researchers’ first clue regarding heme’s role in AML arose from a computer search. The team searched a genomic database for other genes that were abnormally switched on in MYCN-driven AML.

They found that UROD was highly activated and noted that UROD is part of the molecular machinery that synthesizes heme.

Especially significant, Dr Schuetz said, was the finding that MYCN-driven AML with the most over-activated UROD was far more lethal than other AMLs.

The researchers found that cells with over-activated MYCN consumed more oxygen and depended on the production of heme for self-renewal and oncogenic transformation. But the team was able to block cancer cell self-renewal in the MYCN cells by blocking heme synthesis.

The researchers also found they could suppress self-renewal by blocking ABCG2, a “relief-valve” molecule that rids the cells of porphyrin, a building-block molecule of heme.

Blocking ABCG2 caused the buildup of porphyrin, which is toxic to the leukemia cells. However, blocking ABCG2 in normal cells produced no ill effects.

In mouse models of MYCN leukemia, the researchers tested a strategy of knocking out ABCG2. These knockout mice had significantly slower disease progression and longer survival.

What’s more, the team found they could cure leukemia in these mice by inhibiting ABCG2 and ramping up the heme machinery.

“Our findings suggest 2 drug strategies to treat AML,” Dr Schuetz said. “One would be to target UROD, which would reduce heme biosynthesis. Such drugs would selectively affect leukemia cells because they are so dependent on heme.”

“The other strategy would be to use drugs to inhibit the relief-valve protein and, at the same time, administer a chemical that is a precursor of heme. This would cause a buildup of toxic molecules that are part of the heme synthesis pathway.”

Dr Schuetz said other cancers with an over-activated heme pathway might also be vulnerable to such a treatment strategy.

He and his colleagues plan to extend their understanding of the heme machinery in AML with further studies. For example, they don’t know whether heme’s role in cell respiration is the only important one in supporting AML progression, since heme plays a wide range of roles in cells.

The researchers are also planning to test whether drugs that suppress UROD function in the heme-production machinery can effectively battle AML.

Henrique Orlandi Mourao

Researchers have found evidence to suggest that a type of acute myeloid leukemia (AML) depends on the production of heme.

The group’s work has revealed 2 ways to target heme synthesis that might be used to treat this type of AML, which is driven by the oncogene MYCN.

John Schuetz, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee, and his colleague described this research in JCI Insight.

Previous research had suggested that heme production was affected in leukemia.

However, Dr Schuetz said, “Absolutely nothing was known about the role of heme biosynthesis [in AML] before our work.”

The researchers’ first clue regarding heme’s role in AML arose from a computer search. The team searched a genomic database for other genes that were abnormally switched on in MYCN-driven AML.

They found that UROD was highly activated and noted that UROD is part of the molecular machinery that synthesizes heme.

Especially significant, Dr Schuetz said, was the finding that MYCN-driven AML with the most over-activated UROD was far more lethal than other AMLs.

The researchers found that cells with over-activated MYCN consumed more oxygen and depended on the production of heme for self-renewal and oncogenic transformation. But the team was able to block cancer cell self-renewal in the MYCN cells by blocking heme synthesis.

The researchers also found they could suppress self-renewal by blocking ABCG2, a “relief-valve” molecule that rids the cells of porphyrin, a building-block molecule of heme.

Blocking ABCG2 caused the buildup of porphyrin, which is toxic to the leukemia cells. However, blocking ABCG2 in normal cells produced no ill effects.

In mouse models of MYCN leukemia, the researchers tested a strategy of knocking out ABCG2. These knockout mice had significantly slower disease progression and longer survival.

What’s more, the team found they could cure leukemia in these mice by inhibiting ABCG2 and ramping up the heme machinery.

“Our findings suggest 2 drug strategies to treat AML,” Dr Schuetz said. “One would be to target UROD, which would reduce heme biosynthesis. Such drugs would selectively affect leukemia cells because they are so dependent on heme.”

“The other strategy would be to use drugs to inhibit the relief-valve protein and, at the same time, administer a chemical that is a precursor of heme. This would cause a buildup of toxic molecules that are part of the heme synthesis pathway.”

Dr Schuetz said other cancers with an over-activated heme pathway might also be vulnerable to such a treatment strategy.

He and his colleagues plan to extend their understanding of the heme machinery in AML with further studies. For example, they don’t know whether heme’s role in cell respiration is the only important one in supporting AML progression, since heme plays a wide range of roles in cells.

The researchers are also planning to test whether drugs that suppress UROD function in the heme-production machinery can effectively battle AML.

Henrique Orlandi Mourao

Researchers have found evidence to suggest that a type of acute myeloid leukemia (AML) depends on the production of heme.

The group’s work has revealed 2 ways to target heme synthesis that might be used to treat this type of AML, which is driven by the oncogene MYCN.

John Schuetz, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee, and his colleague described this research in JCI Insight.

Previous research had suggested that heme production was affected in leukemia.

However, Dr Schuetz said, “Absolutely nothing was known about the role of heme biosynthesis [in AML] before our work.”

The researchers’ first clue regarding heme’s role in AML arose from a computer search. The team searched a genomic database for other genes that were abnormally switched on in MYCN-driven AML.

They found that UROD was highly activated and noted that UROD is part of the molecular machinery that synthesizes heme.

Especially significant, Dr Schuetz said, was the finding that MYCN-driven AML with the most over-activated UROD was far more lethal than other AMLs.

The researchers found that cells with over-activated MYCN consumed more oxygen and depended on the production of heme for self-renewal and oncogenic transformation. But the team was able to block cancer cell self-renewal in the MYCN cells by blocking heme synthesis.

The researchers also found they could suppress self-renewal by blocking ABCG2, a “relief-valve” molecule that rids the cells of porphyrin, a building-block molecule of heme.

Blocking ABCG2 caused the buildup of porphyrin, which is toxic to the leukemia cells. However, blocking ABCG2 in normal cells produced no ill effects.

In mouse models of MYCN leukemia, the researchers tested a strategy of knocking out ABCG2. These knockout mice had significantly slower disease progression and longer survival.

What’s more, the team found they could cure leukemia in these mice by inhibiting ABCG2 and ramping up the heme machinery.

“Our findings suggest 2 drug strategies to treat AML,” Dr Schuetz said. “One would be to target UROD, which would reduce heme biosynthesis. Such drugs would selectively affect leukemia cells because they are so dependent on heme.”

“The other strategy would be to use drugs to inhibit the relief-valve protein and, at the same time, administer a chemical that is a precursor of heme. This would cause a buildup of toxic molecules that are part of the heme synthesis pathway.”

Dr Schuetz said other cancers with an over-activated heme pathway might also be vulnerable to such a treatment strategy.

He and his colleagues plan to extend their understanding of the heme machinery in AML with further studies. For example, they don’t know whether heme’s role in cell respiration is the only important one in supporting AML progression, since heme plays a wide range of roles in cells.

The researchers are also planning to test whether drugs that suppress UROD function in the heme-production machinery can effectively battle AML.

Photo by Diane Reid

A new study suggests patients with advanced cancer who suffer cardiac arrest in the hospital have a survival rate of less than 10%, which is about half the rate of patients without cancer who suffer cardiac arrest.

This finding helps to clear up some myths about cardiac arrest survival and can be used as a guidepost when hospitalized cancer patients and their families consider do-not-resuscitate (DNR) orders, said Jeffrey T. Bruckel, MD, of the University of Rochester Medical Center in New York.

“We’re hopeful that our study, in some way, will help doctors and cancer patients make more informed decisions about the end of life,” Dr Bruckel said. “It’s very important to have early, frank discussions around the goals of care.”

Dr Bruckel and his colleagues published their study in the Journal of Oncology Practice.

The researchers used a US-wide resuscitation registry to evaluate survival after cardiac arrest in patients treated at 369 hospitals.

The study excluded patients with implantable defibrillators and those who were admitted for surgery, emergency room treatment, rehabilitation, or treatment from cardiac catheterization labs or interventional radiology.

Of the 47,157 eligible patients who experienced cardiac arrest, 14% (n=6585) had advanced cancer, including hematologic malignancies.

After cardiac arrest, 57.5% of the advanced cancer patients were resuscitated successfully, as were 63% of non-cancer patients (P<0.001).

After resuscitation, 9.6% of the cancer patients survived to be discharged, compared to 19.2% of non-cancer patients (P<0.001).

When the researchers adjusted their analysis for potential confounders, results were similar. The rate of successful resuscitation was 52.3% in advanced cancer patients and 56.6% in non-cancer patients (P<0.001). The rate of survival to discharge was 7.4% and 13.4%, respectively (P<0.001).

Dr Bruckel said there was no evidence to suggest that patients with advanced cancer received less aggressive resuscitation care.

However, there was a significant difference in the mean duration of resuscitation time among non-survivors with cancer—22.5 minutes—and non-survivors without cancer—24.2 minutes (P<0.001). After adjustment, the mean duration of resuscitation was 22.5 minutes and 24.1 minutes, respectively (P<0.001).

Cancer patients were more likely than those without cancer to sign DNR orders after resuscitation—55.6% and 43%, respectively (P<0.001). Results were similar after adjustment—50.4% and 41.6%, respectively (P<0.001).

Dr Bruckel and his colleagues said there were several limitations to this study, including a lack of detailed data on the types of advanced cancer and cancer treatments being given at the time of cardiac arrest.

Therefore, the next step in advancing this work is to gather data on the types of cancer diagnosis and treatment plans of patients who undergo in-hospital cardiac arrest.

Dr Bruckel also believes it is important to know how patients feel about this data and how both patients and physicians are using this data in decision-making.

“A large component of end-of-life care involves patient and family care decision-making, and a lot of that is driven by the routine discussions that we have,” Dr Bruckel said. “Not every patient is going to want detailed information, but for those that do, it’s important to have it. It’s important to tell them what we know.” 

Photo by Diane Reid

A new study suggests patients with advanced cancer who suffer cardiac arrest in the hospital have a survival rate of less than 10%, which is about half the rate of patients without cancer who suffer cardiac arrest.

This finding helps to clear up some myths about cardiac arrest survival and can be used as a guidepost when hospitalized cancer patients and their families consider do-not-resuscitate (DNR) orders, said Jeffrey T. Bruckel, MD, of the University of Rochester Medical Center in New York.

“We’re hopeful that our study, in some way, will help doctors and cancer patients make more informed decisions about the end of life,” Dr Bruckel said. “It’s very important to have early, frank discussions around the goals of care.”

Dr Bruckel and his colleagues published their study in the Journal of Oncology Practice.

The researchers used a US-wide resuscitation registry to evaluate survival after cardiac arrest in patients treated at 369 hospitals.

The study excluded patients with implantable defibrillators and those who were admitted for surgery, emergency room treatment, rehabilitation, or treatment from cardiac catheterization labs or interventional radiology.

Of the 47,157 eligible patients who experienced cardiac arrest, 14% (n=6585) had advanced cancer, including hematologic malignancies.

After cardiac arrest, 57.5% of the advanced cancer patients were resuscitated successfully, as were 63% of non-cancer patients (P<0.001).

After resuscitation, 9.6% of the cancer patients survived to be discharged, compared to 19.2% of non-cancer patients (P<0.001).

When the researchers adjusted their analysis for potential confounders, results were similar. The rate of successful resuscitation was 52.3% in advanced cancer patients and 56.6% in non-cancer patients (P<0.001). The rate of survival to discharge was 7.4% and 13.4%, respectively (P<0.001).

Dr Bruckel said there was no evidence to suggest that patients with advanced cancer received less aggressive resuscitation care.

However, there was a significant difference in the mean duration of resuscitation time among non-survivors with cancer—22.5 minutes—and non-survivors without cancer—24.2 minutes (P<0.001). After adjustment, the mean duration of resuscitation was 22.5 minutes and 24.1 minutes, respectively (P<0.001).

Cancer patients were more likely than those without cancer to sign DNR orders after resuscitation—55.6% and 43%, respectively (P<0.001). Results were similar after adjustment—50.4% and 41.6%, respectively (P<0.001).

Dr Bruckel and his colleagues said there were several limitations to this study, including a lack of detailed data on the types of advanced cancer and cancer treatments being given at the time of cardiac arrest.

Therefore, the next step in advancing this work is to gather data on the types of cancer diagnosis and treatment plans of patients who undergo in-hospital cardiac arrest.

Dr Bruckel also believes it is important to know how patients feel about this data and how both patients and physicians are using this data in decision-making.

“A large component of end-of-life care involves patient and family care decision-making, and a lot of that is driven by the routine discussions that we have,” Dr Bruckel said. “Not every patient is going to want detailed information, but for those that do, it’s important to have it. It’s important to tell them what we know.” 

Photo by Diane Reid

A new study suggests patients with advanced cancer who suffer cardiac arrest in the hospital have a survival rate of less than 10%, which is about half the rate of patients without cancer who suffer cardiac arrest.

This finding helps to clear up some myths about cardiac arrest survival and can be used as a guidepost when hospitalized cancer patients and their families consider do-not-resuscitate (DNR) orders, said Jeffrey T. Bruckel, MD, of the University of Rochester Medical Center in New York.

“We’re hopeful that our study, in some way, will help doctors and cancer patients make more informed decisions about the end of life,” Dr Bruckel said. “It’s very important to have early, frank discussions around the goals of care.”

Dr Bruckel and his colleagues published their study in the Journal of Oncology Practice.

The researchers used a US-wide resuscitation registry to evaluate survival after cardiac arrest in patients treated at 369 hospitals.

The study excluded patients with implantable defibrillators and those who were admitted for surgery, emergency room treatment, rehabilitation, or treatment from cardiac catheterization labs or interventional radiology.

Of the 47,157 eligible patients who experienced cardiac arrest, 14% (n=6585) had advanced cancer, including hematologic malignancies.

After cardiac arrest, 57.5% of the advanced cancer patients were resuscitated successfully, as were 63% of non-cancer patients (P<0.001).

After resuscitation, 9.6% of the cancer patients survived to be discharged, compared to 19.2% of non-cancer patients (P<0.001).

When the researchers adjusted their analysis for potential confounders, results were similar. The rate of successful resuscitation was 52.3% in advanced cancer patients and 56.6% in non-cancer patients (P<0.001). The rate of survival to discharge was 7.4% and 13.4%, respectively (P<0.001).

Dr Bruckel said there was no evidence to suggest that patients with advanced cancer received less aggressive resuscitation care.

However, there was a significant difference in the mean duration of resuscitation time among non-survivors with cancer—22.5 minutes—and non-survivors without cancer—24.2 minutes (P<0.001). After adjustment, the mean duration of resuscitation was 22.5 minutes and 24.1 minutes, respectively (P<0.001).

Cancer patients were more likely than those without cancer to sign DNR orders after resuscitation—55.6% and 43%, respectively (P<0.001). Results were similar after adjustment—50.4% and 41.6%, respectively (P<0.001).

Dr Bruckel and his colleagues said there were several limitations to this study, including a lack of detailed data on the types of advanced cancer and cancer treatments being given at the time of cardiac arrest.

Therefore, the next step in advancing this work is to gather data on the types of cancer diagnosis and treatment plans of patients who undergo in-hospital cardiac arrest.

Dr Bruckel also believes it is important to know how patients feel about this data and how both patients and physicians are using this data in decision-making.

“A large component of end-of-life care involves patient and family care decision-making, and a lot of that is driven by the routine discussions that we have,” Dr Bruckel said. “Not every patient is going to want detailed information, but for those that do, it’s important to have it. It’s important to tell them what we know.” 

Photo by Darren Baker

A database containing information on more than 11,000 tumors is now available to researchers studying pediatric cancers.

The database was created as part of UC Santa Cruz Genomics Institute’s Treehouse Childhood Cancer Initiative.

The goal of this initiative is to allow researchers to analyze their patients’ data alongside data from thousands of patients with pediatric and adult cancers, including leukemias and lymphomas.

The intention is to help researchers find hidden causes of cancer that may be missed when they analyze a patient’s data in isolation.

The database, which is available at https://treehouse.xenahubs.net, contains RNA-sequencing gene expression data, as well as information on patients’ age, sex, and disease.

Photo by Darren Baker

A database containing information on more than 11,000 tumors is now available to researchers studying pediatric cancers.

The database was created as part of UC Santa Cruz Genomics Institute’s Treehouse Childhood Cancer Initiative.

The goal of this initiative is to allow researchers to analyze their patients’ data alongside data from thousands of patients with pediatric and adult cancers, including leukemias and lymphomas.

The intention is to help researchers find hidden causes of cancer that may be missed when they analyze a patient’s data in isolation.

The database, which is available at https://treehouse.xenahubs.net, contains RNA-sequencing gene expression data, as well as information on patients’ age, sex, and disease.

Photo by Darren Baker

A database containing information on more than 11,000 tumors is now available to researchers studying pediatric cancers.

The database was created as part of UC Santa Cruz Genomics Institute’s Treehouse Childhood Cancer Initiative.

The goal of this initiative is to allow researchers to analyze their patients’ data alongside data from thousands of patients with pediatric and adult cancers, including leukemias and lymphomas.

The intention is to help researchers find hidden causes of cancer that may be missed when they analyze a patient’s data in isolation.

The database, which is available at https://treehouse.xenahubs.net, contains RNA-sequencing gene expression data, as well as information on patients’ age, sex, and disease.

Photo by Bill Branson

Neuroscientists say they have uncovered genetic differences between radiation-induced meningiomas (RIMs) and sporadic meningiomas (SMs).

Their work suggests RIMs have a different “mutational landscape” from SMs, a finding that may have “significant therapeutic implications” for childhood cancer survivors who undergo cranial radiation.

Gelareh Zadeh, MD, PhD, of the University of Toronto in Ontario, Canada, and her colleagues reported these findings in Nature Communications.

“Radiation-induced meningiomas appear the same [as SMs] on MRI and pathology, feel the same during surgery, and look the same under the operating microscope,” Dr Zadeh said.

“What’s different is they are more aggressive, tend to recur in multiples, and invade the brain, causing significant morbidity and limitations (or impairments) for individuals who survive following childhood radiation. By understanding the biology, the goal is to identify a therapeutic strategy that could be implemented early on after childhood radiation to prevent the formation of these tumors in the first place.”

To better understand the biology, Dr Zadeh and her colleagues analyzed 31 RIMs. This included 18 tumors from 16 patients with childhood cancers, 9 with leukemia.

The researchers found NF2 gene rearrangements in 12 of the RIMs and noted that such rearrangements have not been observed in SMs.

On the other hand, recurrent mutations characteristic of SMs—AKT1, KLF4, TRAF7, and SMO—were not found in the RIMs.

The researchers also noted that, overall, chromosomal aberrations in RIMs were more complex than those observed in SMs. And combined loss of chromosomes 1p and 22q was common in RIMs (16/18).

“Our research identified a specific rearrangement involving the NF2 gene that causes radiation-induced meningiomas,” said Kenneth Aldape, MD, of University Health Network in Toronto.

“But there are likely other genetic rearrangements that are occurring as a result of that radiation-induced DNA damage. So one of the next steps is to identify what the radiation is doing to the DNA of the meninges.”

“In addition, identifying the subset of childhood cancer patients who are at highest risk to develop meningioma is critical so that they could be followed closely for early detection and management.”

Photo by Bill Branson

Neuroscientists say they have uncovered genetic differences between radiation-induced meningiomas (RIMs) and sporadic meningiomas (SMs).

Their work suggests RIMs have a different “mutational landscape” from SMs, a finding that may have “significant therapeutic implications” for childhood cancer survivors who undergo cranial radiation.

Gelareh Zadeh, MD, PhD, of the University of Toronto in Ontario, Canada, and her colleagues reported these findings in Nature Communications.

“Radiation-induced meningiomas appear the same [as SMs] on MRI and pathology, feel the same during surgery, and look the same under the operating microscope,” Dr Zadeh said.

“What’s different is they are more aggressive, tend to recur in multiples, and invade the brain, causing significant morbidity and limitations (or impairments) for individuals who survive following childhood radiation. By understanding the biology, the goal is to identify a therapeutic strategy that could be implemented early on after childhood radiation to prevent the formation of these tumors in the first place.”

To better understand the biology, Dr Zadeh and her colleagues analyzed 31 RIMs. This included 18 tumors from 16 patients with childhood cancers, 9 with leukemia.

The researchers found NF2 gene rearrangements in 12 of the RIMs and noted that such rearrangements have not been observed in SMs.

On the other hand, recurrent mutations characteristic of SMs—AKT1, KLF4, TRAF7, and SMO—were not found in the RIMs.

The researchers also noted that, overall, chromosomal aberrations in RIMs were more complex than those observed in SMs. And combined loss of chromosomes 1p and 22q was common in RIMs (16/18).

“Our research identified a specific rearrangement involving the NF2 gene that causes radiation-induced meningiomas,” said Kenneth Aldape, MD, of University Health Network in Toronto.

“But there are likely other genetic rearrangements that are occurring as a result of that radiation-induced DNA damage. So one of the next steps is to identify what the radiation is doing to the DNA of the meninges.”

“In addition, identifying the subset of childhood cancer patients who are at highest risk to develop meningioma is critical so that they could be followed closely for early detection and management.”

Photo by Bill Branson

Neuroscientists say they have uncovered genetic differences between radiation-induced meningiomas (RIMs) and sporadic meningiomas (SMs).

Their work suggests RIMs have a different “mutational landscape” from SMs, a finding that may have “significant therapeutic implications” for childhood cancer survivors who undergo cranial radiation.

Gelareh Zadeh, MD, PhD, of the University of Toronto in Ontario, Canada, and her colleagues reported these findings in Nature Communications.

“Radiation-induced meningiomas appear the same [as SMs] on MRI and pathology, feel the same during surgery, and look the same under the operating microscope,” Dr Zadeh said.

“What’s different is they are more aggressive, tend to recur in multiples, and invade the brain, causing significant morbidity and limitations (or impairments) for individuals who survive following childhood radiation. By understanding the biology, the goal is to identify a therapeutic strategy that could be implemented early on after childhood radiation to prevent the formation of these tumors in the first place.”

To better understand the biology, Dr Zadeh and her colleagues analyzed 31 RIMs. This included 18 tumors from 16 patients with childhood cancers, 9 with leukemia.

The researchers found NF2 gene rearrangements in 12 of the RIMs and noted that such rearrangements have not been observed in SMs.

On the other hand, recurrent mutations characteristic of SMs—AKT1, KLF4, TRAF7, and SMO—were not found in the RIMs.

The researchers also noted that, overall, chromosomal aberrations in RIMs were more complex than those observed in SMs. And combined loss of chromosomes 1p and 22q was common in RIMs (16/18).

“Our research identified a specific rearrangement involving the NF2 gene that causes radiation-induced meningiomas,” said Kenneth Aldape, MD, of University Health Network in Toronto.

“But there are likely other genetic rearrangements that are occurring as a result of that radiation-induced DNA damage. So one of the next steps is to identify what the radiation is doing to the DNA of the meninges.”

“In addition, identifying the subset of childhood cancer patients who are at highest risk to develop meningioma is critical so that they could be followed closely for early detection and management.”

Photo by Bill Branson

Consolidation therapy that includes arsenic trioxide (ATO) can decrease anthracycline dosing by about 40% in children and young adults with acute promyelocytic leukemia (APL), according to new research.

And it can accomplish this without compromising survival in standard-risk patients.

Outcomes for high-risk patients compared favorably to other pediatric APL trials, the research indicated.

Investigators compared ATO consolidation in the AAML0631 trial to the historic control trial AIDA0493 and reported the results in the Journal of Clinical Oncology.

The AAML0631 phase 3 trial, conducted by the Children’s Oncology Group, compared newly diagnosed pediatric APL patients receiving ATO consolidation to the benchmark of event-free survival (EFS) in standard-risk (SR) patients established by the AIDA0493 trial.

AIDA0493 enrolled patients between January 1993 and June 2000. The protocol involved treatment with all-trans retinoic acid (ATRA), anthracyclines, and high-dose cytarabine. The trial resulted in overall survival (OS) of approximately 90%.

AAML0631

AAML063 investigators defined SR as a white blood cell count (WBC) at presentation less than 10,000 cells/μL. They defined high risk (HR) as a WBC count of 10,000 cells/μL or more.

AAML0631 patients had to be at least 2 years old and younger than 22, and their de novo APL had to be confirmed by PML-RARα polymerase chain reaction.

The patients could have had no prior leukemia treatment, except for steroids, hydroxyurea, or leukapheresis.

AAML0631 did not exclude patients based on organ function or performance status. AIDA0493, however, excluded patients with performance status of 4 or liver function tests greater than 3 times the upper limit of normal.

Patients were excluded from AAML0631 if they had preexisting prolonged QT syndrome because of the risk of QT interval prolongation with ATO.

AAML0631 treatment protocol

All patients received ATRA during induction, each consolidation course, and maintenance.

Induction therapy consisted of ATRA and idarubicin.

All patients received 2 cycles of ATO during the first consolidation. SR patients received an additional 2 consolidation courses, and HR patients received 3 consolidation courses that included high-dose cytarabine and anthracycline.

Maintenance therapy consisted of ATRA, oral methotrexate, and 6-mercaptopurine for 2 years.

Patients also received prophylactic treatment with intrathecal cytarabine.

Patient demographics

Investigators enrolled 108 patients between March 2009 and November 2012, of which 101 (66 SR and 35 HR) were evaluable.

Patients were a median age of 15.04 years (range, 2.01 – 21.34), 56% were female, 80% were white, 10% black, 2% Native American, 3% Asian, and 5% unknown.

Three quarters of the patients had an ECOG score of 0 or 1, median WBC counts of 3.8 x 1000 cells/uL (range, 0.4 – 173.8), and median platelet counts of 21.5 x 1000/uL (range, 3 – 198).

Almost two-thirds of patients (63%) had the classic translocation (15;17), and 37% had an additional 1 or more cytogenetic abnormalities.

The SR patients in AAML0631 had similar characteristics to the patients in AIDA0493 except for the distribution of performance status scores and differences in racial/ethnic diversity.

Efficacy

After a median follow-up of 3.73 years (range, 0.003 – 5.97), the 3-year overall survival (OS) was 94% ± 5% and the 3-year EFS was 91% ± 6%.

For SR patients, the OS was 98% ± 3% and the EFS 95% ± 5%.

For HR patients, the OS was 86% ± 12% and the EFS was 83% ± 13%.

SR patients had a 2-year EFS of 97%. This compared with 91% for patients in the AIDA0493 trial, which means that therapy with ATO was not inferior to therapy in the historic comparator trial (P=0.93).

And these results were achieved with a cumulative anthracycline dosing of idarubicin at 51 mg/m² (SR) and 61 mg/m² (HR) and mitoxantrone at 20 mg/m².

This compared with the AIDA0493 cumulative anthracycline dosing of 80 mg/m² of idarubicin and 50 mg/m² of mitoxantrone.

The cumulative daunorubicin equivalent in the AAML0631 trial was 335 mg/m² (SR) and 385 mg/m² (HR) compared with 600 mg/m² in the AIDA 0493 trial.

Toxicity

The percentage of patients with adverse events varied according to treatment cycle and was highest during induction and high-dose cytarabine-containing courses.

The most common adverse events were fever/neutropenia and infection.

Differentiation syndrome occurred in 20% of patients during induction, 31% in HR patients and 13% in SR patients. ATRA was held for 15 of these patients during induction. It was subsequently re-started at a lower dose and increased to the full dose.

QTc interval prolongation of grade 1 or 2 occurred in 16% (n=15) and 12% (n=11) during the ATO cycles.

One patient experienced grade 3 QTc interval prolongation during ATO consolidation. There were no grade 4 or 5 events for this toxicity.

One event of grade 1 ventricular arrhythmia and 1 event of grade 1 left ventricular systolic dysfunction occurred during ATO consolidation.

Two off-therapy cardiac events have been reported: a grade 1 QTc interval prolongation and a grade 2 ventricular arrhythmia.

No cardiac deaths have occurred, and liver toxicity was minimal during ATO cycles.

The investigators believe the favorable results of this study provide a new benchmark for outcomes in pediatric APL.

The Children’s Oncology Group is currently accruing pediatric APL patients to further investigate similar treatment approaches. 

Photo by Bill Branson

Consolidation therapy that includes arsenic trioxide (ATO) can decrease anthracycline dosing by about 40% in children and young adults with acute promyelocytic leukemia (APL), according to new research.

And it can accomplish this without compromising survival in standard-risk patients.

Outcomes for high-risk patients compared favorably to other pediatric APL trials, the research indicated.

Investigators compared ATO consolidation in the AAML0631 trial to the historic control trial AIDA0493 and reported the results in the Journal of Clinical Oncology.

The AAML0631 phase 3 trial, conducted by the Children’s Oncology Group, compared newly diagnosed pediatric APL patients receiving ATO consolidation to the benchmark of event-free survival (EFS) in standard-risk (SR) patients established by the AIDA0493 trial.

AIDA0493 enrolled patients between January 1993 and June 2000. The protocol involved treatment with all-trans retinoic acid (ATRA), anthracyclines, and high-dose cytarabine. The trial resulted in overall survival (OS) of approximately 90%.

AAML0631

AAML063 investigators defined SR as a white blood cell count (WBC) at presentation less than 10,000 cells/μL. They defined high risk (HR) as a WBC count of 10,000 cells/μL or more.

AAML0631 patients had to be at least 2 years old and younger than 22, and their de novo APL had to be confirmed by PML-RARα polymerase chain reaction.

The patients could have had no prior leukemia treatment, except for steroids, hydroxyurea, or leukapheresis.

AAML0631 did not exclude patients based on organ function or performance status. AIDA0493, however, excluded patients with performance status of 4 or liver function tests greater than 3 times the upper limit of normal.

Patients were excluded from AAML0631 if they had preexisting prolonged QT syndrome because of the risk of QT interval prolongation with ATO.

AAML0631 treatment protocol

All patients received ATRA during induction, each consolidation course, and maintenance.

Induction therapy consisted of ATRA and idarubicin.

All patients received 2 cycles of ATO during the first consolidation. SR patients received an additional 2 consolidation courses, and HR patients received 3 consolidation courses that included high-dose cytarabine and anthracycline.

Maintenance therapy consisted of ATRA, oral methotrexate, and 6-mercaptopurine for 2 years.

Patients also received prophylactic treatment with intrathecal cytarabine.

Patient demographics

Investigators enrolled 108 patients between March 2009 and November 2012, of which 101 (66 SR and 35 HR) were evaluable.

Patients were a median age of 15.04 years (range, 2.01 – 21.34), 56% were female, 80% were white, 10% black, 2% Native American, 3% Asian, and 5% unknown.

Three quarters of the patients had an ECOG score of 0 or 1, median WBC counts of 3.8 x 1000 cells/uL (range, 0.4 – 173.8), and median platelet counts of 21.5 x 1000/uL (range, 3 – 198).

Almost two-thirds of patients (63%) had the classic translocation (15;17), and 37% had an additional 1 or more cytogenetic abnormalities.

The SR patients in AAML0631 had similar characteristics to the patients in AIDA0493 except for the distribution of performance status scores and differences in racial/ethnic diversity.

Efficacy

After a median follow-up of 3.73 years (range, 0.003 – 5.97), the 3-year overall survival (OS) was 94% ± 5% and the 3-year EFS was 91% ± 6%.

For SR patients, the OS was 98% ± 3% and the EFS 95% ± 5%.

For HR patients, the OS was 86% ± 12% and the EFS was 83% ± 13%.

SR patients had a 2-year EFS of 97%. This compared with 91% for patients in the AIDA0493 trial, which means that therapy with ATO was not inferior to therapy in the historic comparator trial (P=0.93).

And these results were achieved with a cumulative anthracycline dosing of idarubicin at 51 mg/m² (SR) and 61 mg/m² (HR) and mitoxantrone at 20 mg/m².

This compared with the AIDA0493 cumulative anthracycline dosing of 80 mg/m² of idarubicin and 50 mg/m² of mitoxantrone.

The cumulative daunorubicin equivalent in the AAML0631 trial was 335 mg/m² (SR) and 385 mg/m² (HR) compared with 600 mg/m² in the AIDA 0493 trial.

Toxicity

The percentage of patients with adverse events varied according to treatment cycle and was highest during induction and high-dose cytarabine-containing courses.

The most common adverse events were fever/neutropenia and infection.

Differentiation syndrome occurred in 20% of patients during induction, 31% in HR patients and 13% in SR patients. ATRA was held for 15 of these patients during induction. It was subsequently re-started at a lower dose and increased to the full dose.

QTc interval prolongation of grade 1 or 2 occurred in 16% (n=15) and 12% (n=11) during the ATO cycles.

One patient experienced grade 3 QTc interval prolongation during ATO consolidation. There were no grade 4 or 5 events for this toxicity.

One event of grade 1 ventricular arrhythmia and 1 event of grade 1 left ventricular systolic dysfunction occurred during ATO consolidation.

Two off-therapy cardiac events have been reported: a grade 1 QTc interval prolongation and a grade 2 ventricular arrhythmia.

No cardiac deaths have occurred, and liver toxicity was minimal during ATO cycles.

The investigators believe the favorable results of this study provide a new benchmark for outcomes in pediatric APL.

The Children’s Oncology Group is currently accruing pediatric APL patients to further investigate similar treatment approaches. 

Photo by Bill Branson

Consolidation therapy that includes arsenic trioxide (ATO) can decrease anthracycline dosing by about 40% in children and young adults with acute promyelocytic leukemia (APL), according to new research.

And it can accomplish this without compromising survival in standard-risk patients.

Outcomes for high-risk patients compared favorably to other pediatric APL trials, the research indicated.

Investigators compared ATO consolidation in the AAML0631 trial to the historic control trial AIDA0493 and reported the results in the Journal of Clinical Oncology.

The AAML0631 phase 3 trial, conducted by the Children’s Oncology Group, compared newly diagnosed pediatric APL patients receiving ATO consolidation to the benchmark of event-free survival (EFS) in standard-risk (SR) patients established by the AIDA0493 trial.

AIDA0493 enrolled patients between January 1993 and June 2000. The protocol involved treatment with all-trans retinoic acid (ATRA), anthracyclines, and high-dose cytarabine. The trial resulted in overall survival (OS) of approximately 90%.

AAML0631

AAML063 investigators defined SR as a white blood cell count (WBC) at presentation less than 10,000 cells/μL. They defined high risk (HR) as a WBC count of 10,000 cells/μL or more.

AAML0631 patients had to be at least 2 years old and younger than 22, and their de novo APL had to be confirmed by PML-RARα polymerase chain reaction.

The patients could have had no prior leukemia treatment, except for steroids, hydroxyurea, or leukapheresis.

AAML0631 did not exclude patients based on organ function or performance status. AIDA0493, however, excluded patients with performance status of 4 or liver function tests greater than 3 times the upper limit of normal.

Patients were excluded from AAML0631 if they had preexisting prolonged QT syndrome because of the risk of QT interval prolongation with ATO.

AAML0631 treatment protocol

All patients received ATRA during induction, each consolidation course, and maintenance.

Induction therapy consisted of ATRA and idarubicin.

All patients received 2 cycles of ATO during the first consolidation. SR patients received an additional 2 consolidation courses, and HR patients received 3 consolidation courses that included high-dose cytarabine and anthracycline.

Maintenance therapy consisted of ATRA, oral methotrexate, and 6-mercaptopurine for 2 years.

Patients also received prophylactic treatment with intrathecal cytarabine.

Patient demographics

Investigators enrolled 108 patients between March 2009 and November 2012, of which 101 (66 SR and 35 HR) were evaluable.

Patients were a median age of 15.04 years (range, 2.01 – 21.34), 56% were female, 80% were white, 10% black, 2% Native American, 3% Asian, and 5% unknown.

Three quarters of the patients had an ECOG score of 0 or 1, median WBC counts of 3.8 x 1000 cells/uL (range, 0.4 – 173.8), and median platelet counts of 21.5 x 1000/uL (range, 3 – 198).

Almost two-thirds of patients (63%) had the classic translocation (15;17), and 37% had an additional 1 or more cytogenetic abnormalities.

The SR patients in AAML0631 had similar characteristics to the patients in AIDA0493 except for the distribution of performance status scores and differences in racial/ethnic diversity.

Efficacy

After a median follow-up of 3.73 years (range, 0.003 – 5.97), the 3-year overall survival (OS) was 94% ± 5% and the 3-year EFS was 91% ± 6%.

For SR patients, the OS was 98% ± 3% and the EFS 95% ± 5%.

For HR patients, the OS was 86% ± 12% and the EFS was 83% ± 13%.

SR patients had a 2-year EFS of 97%. This compared with 91% for patients in the AIDA0493 trial, which means that therapy with ATO was not inferior to therapy in the historic comparator trial (P=0.93).

And these results were achieved with a cumulative anthracycline dosing of idarubicin at 51 mg/m² (SR) and 61 mg/m² (HR) and mitoxantrone at 20 mg/m².

This compared with the AIDA0493 cumulative anthracycline dosing of 80 mg/m² of idarubicin and 50 mg/m² of mitoxantrone.

The cumulative daunorubicin equivalent in the AAML0631 trial was 335 mg/m² (SR) and 385 mg/m² (HR) compared with 600 mg/m² in the AIDA 0493 trial.

Toxicity

The percentage of patients with adverse events varied according to treatment cycle and was highest during induction and high-dose cytarabine-containing courses.

The most common adverse events were fever/neutropenia and infection.

Differentiation syndrome occurred in 20% of patients during induction, 31% in HR patients and 13% in SR patients. ATRA was held for 15 of these patients during induction. It was subsequently re-started at a lower dose and increased to the full dose.

QTc interval prolongation of grade 1 or 2 occurred in 16% (n=15) and 12% (n=11) during the ATO cycles.

One patient experienced grade 3 QTc interval prolongation during ATO consolidation. There were no grade 4 or 5 events for this toxicity.

One event of grade 1 ventricular arrhythmia and 1 event of grade 1 left ventricular systolic dysfunction occurred during ATO consolidation.

Two off-therapy cardiac events have been reported: a grade 1 QTc interval prolongation and a grade 2 ventricular arrhythmia.

No cardiac deaths have occurred, and liver toxicity was minimal during ATO cycles.

The investigators believe the favorable results of this study provide a new benchmark for outcomes in pediatric APL.

The Children’s Oncology Group is currently accruing pediatric APL patients to further investigate similar treatment approaches. 

Photo by Elise Amendola

New research suggests a patient blood management (PBM) program can safely reduce transfusion use in patients with acute leukemia and those undergoing hematopoietic stem cell transplant (HSCT).

The program significantly reduced the use of red blood cell (RBC) and platelet transfusions without increasing morbidity or mortality in patients who were receiving intensive chemotherapy to treat acute leukemia and in patients receiving an allogeneic or autologous HSCT.

“There has been a long-standing belief among hematologists that patients with leukemia undergoing chemotherapy should have a transfusion of red blood cells if their hemoglobin level drops below about 9 g/dL to help avoid adverse outcomes,” said study author Michael Leahy, MB ChB, a consultant hematologist at the University of Western Australia in Perth.

“Findings in this real-world, non-clinical trial setting challenge that belief.”

Dr Leahy and his colleagues published their findings in Transfusion.

The researchers said the PBM program used in this study was built around the “3 pillars” concept of PBM, which are:

• Optimize the patient’s RBC mass
• Minimize blood loss
• Harness and optimize the patient’s physiologic anemia reserve.

No specific transfusion thresholds were established. However, the hospitals did adopt a single-unit RBC transfusion policy for symptomatic anemic patients who were not actively bleeding.

Results

The study included 695 admissions to 2 major hospitals in Western Australia. Patients were admitted between July 2010 and December 2014 for treatment of acute leukemia or for autologous or allogeneic HSCT.

During this time, the patients received 3384 RBC units and 3639 units of platelets.

The mean number of platelet units transfused per hospital admission decreased 35% from baseline to the end of the study period, from 6.3 to 4.1 units (P<0.001).

The mean number of RBC units transfused decreased 39%, from 6.1 to 3.7 (P<0.001). Meanwhile, the use of single-unit RBC transfusions increased from 39% to 67% (P<0.001).

And the mean hemoglobin level prior to RBC transfusion decreased from 8.0 g/dL to 6.8 g/dL (P<0.001).

“This study suggests that patients undergoing chemotherapy with hematological disease may tolerate much lower levels of hemoglobin than previously thought,” said Shannon Farmer, an adjunct research fellow at the University of Western Australia.

“The transfusion threshold, the hemoglobin value at which a transfusion is given, dropped significantly from 8.0 g/dL at the beginning of the study to 6.8 g/dL at the end. This was associated with significant reductions in transfusion and substantial costs savings without evidence of harm to the patients. In fact, it was associated with a trend toward improved survival.”

The reduction in blood products over the study period resulted in a cost savings of AU$694,886 (US$654,007)—AU$389,537 (US$364,177) for RBCs and AU$305,349 (US$289,830) for platelets.

There were no significant changes over the study period in length of hospital stay, serious bleeding events, or in-hospital mortality.

There was a non-significant reduction in the mean length of hospital stay, from 24.5 days to 22.6 days (P=0.338). The difference was still not significant after the researchers adjusted for patient age, patient group, and comorbidities (incident rate ratio=0.88; 95% CI, 0.75-1.04).

The rate of serious bleeding increased over the study period, from 5.3% to 7.0% (P=0.582). After adjustment, the odds ratio was 1.14 (95% CI, 0.38-3.44; P=0.811).

There was a non-significant decrease in in-hospital mortality, from 5.3% to 2.0% (P=0.218). After adjustment, the odds ratio was 0.31 (95% CI, 0.06-1.56; P=0.154).

Based on these results, the researchers concluded that PBM programs could have a substantial impact in this patient population, reducing blood utilization and healthcare costs.

Photo by Elise Amendola

New research suggests a patient blood management (PBM) program can safely reduce transfusion use in patients with acute leukemia and those undergoing hematopoietic stem cell transplant (HSCT).

The program significantly reduced the use of red blood cell (RBC) and platelet transfusions without increasing morbidity or mortality in patients who were receiving intensive chemotherapy to treat acute leukemia and in patients receiving an allogeneic or autologous HSCT.

“There has been a long-standing belief among hematologists that patients with leukemia undergoing chemotherapy should have a transfusion of red blood cells if their hemoglobin level drops below about 9 g/dL to help avoid adverse outcomes,” said study author Michael Leahy, MB ChB, a consultant hematologist at the University of Western Australia in Perth.

“Findings in this real-world, non-clinical trial setting challenge that belief.”

Dr Leahy and his colleagues published their findings in Transfusion.

The researchers said the PBM program used in this study was built around the “3 pillars” concept of PBM, which are:

• Optimize the patient’s RBC mass
• Minimize blood loss
• Harness and optimize the patient’s physiologic anemia reserve.

No specific transfusion thresholds were established. However, the hospitals did adopt a single-unit RBC transfusion policy for symptomatic anemic patients who were not actively bleeding.

Results

The study included 695 admissions to 2 major hospitals in Western Australia. Patients were admitted between July 2010 and December 2014 for treatment of acute leukemia or for autologous or allogeneic HSCT.

During this time, the patients received 3384 RBC units and 3639 units of platelets.

The mean number of platelet units transfused per hospital admission decreased 35% from baseline to the end of the study period, from 6.3 to 4.1 units (P<0.001).

The mean number of RBC units transfused decreased 39%, from 6.1 to 3.7 (P<0.001). Meanwhile, the use of single-unit RBC transfusions increased from 39% to 67% (P<0.001).

And the mean hemoglobin level prior to RBC transfusion decreased from 8.0 g/dL to 6.8 g/dL (P<0.001).

“This study suggests that patients undergoing chemotherapy with hematological disease may tolerate much lower levels of hemoglobin than previously thought,” said Shannon Farmer, an adjunct research fellow at the University of Western Australia.

“The transfusion threshold, the hemoglobin value at which a transfusion is given, dropped significantly from 8.0 g/dL at the beginning of the study to 6.8 g/dL at the end. This was associated with significant reductions in transfusion and substantial costs savings without evidence of harm to the patients. In fact, it was associated with a trend toward improved survival.”

The reduction in blood products over the study period resulted in a cost savings of AU$694,886 (US$654,007)—AU$389,537 (US$364,177) for RBCs and AU$305,349 (US$289,830) for platelets.

There were no significant changes over the study period in length of hospital stay, serious bleeding events, or in-hospital mortality.

There was a non-significant reduction in the mean length of hospital stay, from 24.5 days to 22.6 days (P=0.338). The difference was still not significant after the researchers adjusted for patient age, patient group, and comorbidities (incident rate ratio=0.88; 95% CI, 0.75-1.04).

The rate of serious bleeding increased over the study period, from 5.3% to 7.0% (P=0.582). After adjustment, the odds ratio was 1.14 (95% CI, 0.38-3.44; P=0.811).

There was a non-significant decrease in in-hospital mortality, from 5.3% to 2.0% (P=0.218). After adjustment, the odds ratio was 0.31 (95% CI, 0.06-1.56; P=0.154).

Based on these results, the researchers concluded that PBM programs could have a substantial impact in this patient population, reducing blood utilization and healthcare costs.

Photo by Elise Amendola

New research suggests a patient blood management (PBM) program can safely reduce transfusion use in patients with acute leukemia and those undergoing hematopoietic stem cell transplant (HSCT).

The program significantly reduced the use of red blood cell (RBC) and platelet transfusions without increasing morbidity or mortality in patients who were receiving intensive chemotherapy to treat acute leukemia and in patients receiving an allogeneic or autologous HSCT.

“There has been a long-standing belief among hematologists that patients with leukemia undergoing chemotherapy should have a transfusion of red blood cells if their hemoglobin level drops below about 9 g/dL to help avoid adverse outcomes,” said study author Michael Leahy, MB ChB, a consultant hematologist at the University of Western Australia in Perth.

“Findings in this real-world, non-clinical trial setting challenge that belief.”

Dr Leahy and his colleagues published their findings in Transfusion.

The researchers said the PBM program used in this study was built around the “3 pillars” concept of PBM, which are:

• Optimize the patient’s RBC mass
• Minimize blood loss
• Harness and optimize the patient’s physiologic anemia reserve.

No specific transfusion thresholds were established. However, the hospitals did adopt a single-unit RBC transfusion policy for symptomatic anemic patients who were not actively bleeding.

Results

The study included 695 admissions to 2 major hospitals in Western Australia. Patients were admitted between July 2010 and December 2014 for treatment of acute leukemia or for autologous or allogeneic HSCT.

During this time, the patients received 3384 RBC units and 3639 units of platelets.

The mean number of platelet units transfused per hospital admission decreased 35% from baseline to the end of the study period, from 6.3 to 4.1 units (P<0.001).

The mean number of RBC units transfused decreased 39%, from 6.1 to 3.7 (P<0.001). Meanwhile, the use of single-unit RBC transfusions increased from 39% to 67% (P<0.001).

And the mean hemoglobin level prior to RBC transfusion decreased from 8.0 g/dL to 6.8 g/dL (P<0.001).

“This study suggests that patients undergoing chemotherapy with hematological disease may tolerate much lower levels of hemoglobin than previously thought,” said Shannon Farmer, an adjunct research fellow at the University of Western Australia.

“The transfusion threshold, the hemoglobin value at which a transfusion is given, dropped significantly from 8.0 g/dL at the beginning of the study to 6.8 g/dL at the end. This was associated with significant reductions in transfusion and substantial costs savings without evidence of harm to the patients. In fact, it was associated with a trend toward improved survival.”

The reduction in blood products over the study period resulted in a cost savings of AU$694,886 (US$654,007)—AU$389,537 (US$364,177) for RBCs and AU$305,349 (US$289,830) for platelets.

There were no significant changes over the study period in length of hospital stay, serious bleeding events, or in-hospital mortality.

There was a non-significant reduction in the mean length of hospital stay, from 24.5 days to 22.6 days (P=0.338). The difference was still not significant after the researchers adjusted for patient age, patient group, and comorbidities (incident rate ratio=0.88; 95% CI, 0.75-1.04).

The rate of serious bleeding increased over the study period, from 5.3% to 7.0% (P=0.582). After adjustment, the odds ratio was 1.14 (95% CI, 0.38-3.44; P=0.811).

There was a non-significant decrease in in-hospital mortality, from 5.3% to 2.0% (P=0.218). After adjustment, the odds ratio was 0.31 (95% CI, 0.06-1.56; P=0.154).

Based on these results, the researchers concluded that PBM programs could have a substantial impact in this patient population, reducing blood utilization and healthcare costs.

AML cells

The US Food and Drug Administration (FDA) has granted approval for CPX-351 (Vyxeos™), a fixed-ratio combination of cytarabine and daunorubicin inside a lipid vesicle.

CPX-351 is approved to treat adults with 2 types of acute myeloid leukemia (AML)—AML with myelodysplasia-related changes and newly diagnosed, therapy-related AML.

The FDA granted the approval of CPX-351 to Jazz Pharmaceuticals.

The company says the drug will be commercially available within a week.

The FDA approval of CPX-351 is based on data from a phase 3 trial in which researchers compared CPX-351 to cytarabine and daunorubicin (7+3) in 309 patients, ages 60 to 75, with newly diagnosed, therapy-related AML or AML with myelodysplasia-related changes.

The complete response rate was 38% in the CPX-351 arm and 26% in the 7+3 arm (P=0.036).

The rate of hematopoietic stem cell transplant was 34% in the CPX-351 arm and 25% in the 7+3 arm.

The median overall survival was 9.6 months in the CPX-351 arm and 5.9 months in the 7+3 arm (P=0.005).

All-cause 30-day mortality was 6% in the CPX-351 arm and 11% in the 7+3 arm. Sixty-day mortality was 14% and 21%, respectively.

Six percent of patients in both arms had a fatal adverse event (AE) on treatment or within 30 days of therapy that was not in the setting of progressive disease.

The rate of AEs that led to discontinuation was 18% in the CPX-351 arm and 13% in the 7+3 arm. AEs leading to discontinuation in the CPX-351 arm included prolonged cytopenias, infection, cardiotoxicity, respiratory failure, hemorrhage, renal insufficiency, colitis, and generalized medical deterioration.

The most common AEs (incidence ≥ 25%) in the CPX-351 arm were hemorrhagic events, febrile neutropenia, rash, edema, nausea, mucositis, diarrhea, constipation, musculoskeletal pain, fatigue, abdominal pain, dyspnea, headache, cough, decreased appetite, arrhythmia, pneumonia, bacteremia, chills, sleep disorders, and vomiting.

The most common serious AEs (incidence ≥ 5%) in the CPX-351 arm were dyspnea, myocardial toxicity, sepsis, pneumonia, febrile neutropenia, bacteremia, and hemorrhage.

For more information on CPX-351, visit http://www.vyxeos.com.

AML cells

The US Food and Drug Administration (FDA) has granted approval for CPX-351 (Vyxeos™), a fixed-ratio combination of cytarabine and daunorubicin inside a lipid vesicle.

CPX-351 is approved to treat adults with 2 types of acute myeloid leukemia (AML)—AML with myelodysplasia-related changes and newly diagnosed, therapy-related AML.

The FDA granted the approval of CPX-351 to Jazz Pharmaceuticals.

The company says the drug will be commercially available within a week.

The FDA approval of CPX-351 is based on data from a phase 3 trial in which researchers compared CPX-351 to cytarabine and daunorubicin (7+3) in 309 patients, ages 60 to 75, with newly diagnosed, therapy-related AML or AML with myelodysplasia-related changes.

The complete response rate was 38% in the CPX-351 arm and 26% in the 7+3 arm (P=0.036).

The rate of hematopoietic stem cell transplant was 34% in the CPX-351 arm and 25% in the 7+3 arm.

The median overall survival was 9.6 months in the CPX-351 arm and 5.9 months in the 7+3 arm (P=0.005).

All-cause 30-day mortality was 6% in the CPX-351 arm and 11% in the 7+3 arm. Sixty-day mortality was 14% and 21%, respectively.

Six percent of patients in both arms had a fatal adverse event (AE) on treatment or within 30 days of therapy that was not in the setting of progressive disease.

The rate of AEs that led to discontinuation was 18% in the CPX-351 arm and 13% in the 7+3 arm. AEs leading to discontinuation in the CPX-351 arm included prolonged cytopenias, infection, cardiotoxicity, respiratory failure, hemorrhage, renal insufficiency, colitis, and generalized medical deterioration.

The most common AEs (incidence ≥ 25%) in the CPX-351 arm were hemorrhagic events, febrile neutropenia, rash, edema, nausea, mucositis, diarrhea, constipation, musculoskeletal pain, fatigue, abdominal pain, dyspnea, headache, cough, decreased appetite, arrhythmia, pneumonia, bacteremia, chills, sleep disorders, and vomiting.

The most common serious AEs (incidence ≥ 5%) in the CPX-351 arm were dyspnea, myocardial toxicity, sepsis, pneumonia, febrile neutropenia, bacteremia, and hemorrhage.

For more information on CPX-351, visit http://www.vyxeos.com.

AML cells

The US Food and Drug Administration (FDA) has granted approval for CPX-351 (Vyxeos™), a fixed-ratio combination of cytarabine and daunorubicin inside a lipid vesicle.

CPX-351 is approved to treat adults with 2 types of acute myeloid leukemia (AML)—AML with myelodysplasia-related changes and newly diagnosed, therapy-related AML.

The FDA granted the approval of CPX-351 to Jazz Pharmaceuticals.

The company says the drug will be commercially available within a week.

The FDA approval of CPX-351 is based on data from a phase 3 trial in which researchers compared CPX-351 to cytarabine and daunorubicin (7+3) in 309 patients, ages 60 to 75, with newly diagnosed, therapy-related AML or AML with myelodysplasia-related changes.

The complete response rate was 38% in the CPX-351 arm and 26% in the 7+3 arm (P=0.036).

The rate of hematopoietic stem cell transplant was 34% in the CPX-351 arm and 25% in the 7+3 arm.

The median overall survival was 9.6 months in the CPX-351 arm and 5.9 months in the 7+3 arm (P=0.005).

All-cause 30-day mortality was 6% in the CPX-351 arm and 11% in the 7+3 arm. Sixty-day mortality was 14% and 21%, respectively.

Six percent of patients in both arms had a fatal adverse event (AE) on treatment or within 30 days of therapy that was not in the setting of progressive disease.

The rate of AEs that led to discontinuation was 18% in the CPX-351 arm and 13% in the 7+3 arm. AEs leading to discontinuation in the CPX-351 arm included prolonged cytopenias, infection, cardiotoxicity, respiratory failure, hemorrhage, renal insufficiency, colitis, and generalized medical deterioration.

The most common AEs (incidence ≥ 25%) in the CPX-351 arm were hemorrhagic events, febrile neutropenia, rash, edema, nausea, mucositis, diarrhea, constipation, musculoskeletal pain, fatigue, abdominal pain, dyspnea, headache, cough, decreased appetite, arrhythmia, pneumonia, bacteremia, chills, sleep disorders, and vomiting.

The most common serious AEs (incidence ≥ 5%) in the CPX-351 arm were dyspnea, myocardial toxicity, sepsis, pneumonia, febrile neutropenia, bacteremia, and hemorrhage.

For more information on CPX-351, visit http://www.vyxeos.com.