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Blood disorders prove costly for European economy
chemotherapy
Photo by Rhoda Baer
Malignant and non-malignant blood disorders cost 31 European countries a total of €23 billion in 2012, according to a pair of papers published in The Lancet Haematology.
Healthcare costs accounted for €16 billion of the total costs, with €7 billion for hospital inpatient care and €4 billion for medications.
Informal care (from friends and relatives) cost €1.6 billion, productivity losses due to mortality cost €2.5 billion, and morbidity cost €3 billion.
Researchers determined these figures by analyzing data from international health organizations (WHO and EUROSTAT), as well as national ministries of health and statistical institutes.
The team estimated the economic burden of malignant and non-malignant blood disorders in 2012 for all 28 countries in the European Union (EU), as well as Iceland, Norway, and Switzerland.
The costs considered were healthcare costs (primary care, accident and emergency care, hospital inpatient and outpatient care, and drugs), informal care costs (from friends and relatives), and productivity losses (due to premature death and people being unable to work due to illness).
Malignant blood disorders
In one paper, the researchers noted that the total economic cost of blood cancers to the 31 countries studied was €12 billion in 2012. Healthcare costs measured €7.3 billion (62% of total costs), productivity losses cost €3.6 billion (30%), and informal care cost €1 billion (8%).
In the 28 EU countries, blood cancers represented 8% of the total cancer costs (€143 billion), meaning that blood cancers are the fourth most expensive type of cancer after lung (15%), breast (12%), and colorectal (10%) cancers.
When considering healthcare costs alone, blood cancers were second only to breast cancers (12% vs 13% of healthcare costs for all cancers).
In 2012, blood cancers cost, on average, €14,674 per patient in the EU (€15,126 in all 31 countries), which is almost 2 times higher than the average cost per patient across all cancers (€7929 in the EU).
The researchers said this difference may be due to the longer length of hospital stay observed for patients with blood cancers (14 days, on average, compared to 8 days across all cancers).
Another potential reason is that blood cancers are increasingly treated with complex, long-term treatments (including stem cell transplants, multi-agent chemotherapy, and radiotherapy) and diagnosed via extensive procedures.
The costs of blood cancers varied widely between the countries studied, but the reasons for this were unclear. For instance, the average healthcare costs in Finland were nearly twice as high as in Belgium (€18,014 vs €9596), despite both countries having similar national income per capita.
Non-malignant blood disorders
In the other paper, the researchers said the total economic cost of non-malignant blood disorders to the 31 countries studied was €11 billion in 2012. Healthcare costs accounted for €8 billion (75% of total costs), productivity losses for €2 billion (19%), and informal care for €618 million (6%).
Averaged across the population studied, non-malignant blood disorders represented an annual healthcare cost of €159 per 10 citizens.
“Non-malignant blood disorders cost the European economy nearly as much as all blood cancers combined,” said Jose Leal, DPhil, of the University of Oxford in the UK.
“We found wide differences in the cost of treating blood disorders in different countries, likely linked to the significant differences in the access and delivery of care for patients with blood disorders. Our findings suggest there is a need to harmonize care of blood disorders across Europe in a cost-effective way.” 
chemotherapy
Photo by Rhoda Baer
Malignant and non-malignant blood disorders cost 31 European countries a total of €23 billion in 2012, according to a pair of papers published in The Lancet Haematology.
Healthcare costs accounted for €16 billion of the total costs, with €7 billion for hospital inpatient care and €4 billion for medications.
Informal care (from friends and relatives) cost €1.6 billion, productivity losses due to mortality cost €2.5 billion, and morbidity cost €3 billion.
Researchers determined these figures by analyzing data from international health organizations (WHO and EUROSTAT), as well as national ministries of health and statistical institutes.
The team estimated the economic burden of malignant and non-malignant blood disorders in 2012 for all 28 countries in the European Union (EU), as well as Iceland, Norway, and Switzerland.
The costs considered were healthcare costs (primary care, accident and emergency care, hospital inpatient and outpatient care, and drugs), informal care costs (from friends and relatives), and productivity losses (due to premature death and people being unable to work due to illness).
Malignant blood disorders
In one paper, the researchers noted that the total economic cost of blood cancers to the 31 countries studied was €12 billion in 2012. Healthcare costs measured €7.3 billion (62% of total costs), productivity losses cost €3.6 billion (30%), and informal care cost €1 billion (8%).
In the 28 EU countries, blood cancers represented 8% of the total cancer costs (€143 billion), meaning that blood cancers are the fourth most expensive type of cancer after lung (15%), breast (12%), and colorectal (10%) cancers.
When considering healthcare costs alone, blood cancers were second only to breast cancers (12% vs 13% of healthcare costs for all cancers).
In 2012, blood cancers cost, on average, €14,674 per patient in the EU (€15,126 in all 31 countries), which is almost 2 times higher than the average cost per patient across all cancers (€7929 in the EU).
The researchers said this difference may be due to the longer length of hospital stay observed for patients with blood cancers (14 days, on average, compared to 8 days across all cancers).
Another potential reason is that blood cancers are increasingly treated with complex, long-term treatments (including stem cell transplants, multi-agent chemotherapy, and radiotherapy) and diagnosed via extensive procedures.
The costs of blood cancers varied widely between the countries studied, but the reasons for this were unclear. For instance, the average healthcare costs in Finland were nearly twice as high as in Belgium (€18,014 vs €9596), despite both countries having similar national income per capita.
Non-malignant blood disorders
In the other paper, the researchers said the total economic cost of non-malignant blood disorders to the 31 countries studied was €11 billion in 2012. Healthcare costs accounted for €8 billion (75% of total costs), productivity losses for €2 billion (19%), and informal care for €618 million (6%).
Averaged across the population studied, non-malignant blood disorders represented an annual healthcare cost of €159 per 10 citizens.
“Non-malignant blood disorders cost the European economy nearly as much as all blood cancers combined,” said Jose Leal, DPhil, of the University of Oxford in the UK.
“We found wide differences in the cost of treating blood disorders in different countries, likely linked to the significant differences in the access and delivery of care for patients with blood disorders. Our findings suggest there is a need to harmonize care of blood disorders across Europe in a cost-effective way.”
chemotherapy
Photo by Rhoda Baer
Malignant and non-malignant blood disorders cost 31 European countries a total of €23 billion in 2012, according to a pair of papers published in The Lancet Haematology.
Healthcare costs accounted for €16 billion of the total costs, with €7 billion for hospital inpatient care and €4 billion for medications.
Informal care (from friends and relatives) cost €1.6 billion, productivity losses due to mortality cost €2.5 billion, and morbidity cost €3 billion.
Researchers determined these figures by analyzing data from international health organizations (WHO and EUROSTAT), as well as national ministries of health and statistical institutes.
The team estimated the economic burden of malignant and non-malignant blood disorders in 2012 for all 28 countries in the European Union (EU), as well as Iceland, Norway, and Switzerland.
The costs considered were healthcare costs (primary care, accident and emergency care, hospital inpatient and outpatient care, and drugs), informal care costs (from friends and relatives), and productivity losses (due to premature death and people being unable to work due to illness).
Malignant blood disorders
In one paper, the researchers noted that the total economic cost of blood cancers to the 31 countries studied was €12 billion in 2012. Healthcare costs measured €7.3 billion (62% of total costs), productivity losses cost €3.6 billion (30%), and informal care cost €1 billion (8%).
In the 28 EU countries, blood cancers represented 8% of the total cancer costs (€143 billion), meaning that blood cancers are the fourth most expensive type of cancer after lung (15%), breast (12%), and colorectal (10%) cancers.
When considering healthcare costs alone, blood cancers were second only to breast cancers (12% vs 13% of healthcare costs for all cancers).
In 2012, blood cancers cost, on average, €14,674 per patient in the EU (€15,126 in all 31 countries), which is almost 2 times higher than the average cost per patient across all cancers (€7929 in the EU).
The researchers said this difference may be due to the longer length of hospital stay observed for patients with blood cancers (14 days, on average, compared to 8 days across all cancers).
Another potential reason is that blood cancers are increasingly treated with complex, long-term treatments (including stem cell transplants, multi-agent chemotherapy, and radiotherapy) and diagnosed via extensive procedures.
The costs of blood cancers varied widely between the countries studied, but the reasons for this were unclear. For instance, the average healthcare costs in Finland were nearly twice as high as in Belgium (€18,014 vs €9596), despite both countries having similar national income per capita.
Non-malignant blood disorders
In the other paper, the researchers said the total economic cost of non-malignant blood disorders to the 31 countries studied was €11 billion in 2012. Healthcare costs accounted for €8 billion (75% of total costs), productivity losses for €2 billion (19%), and informal care for €618 million (6%).
Averaged across the population studied, non-malignant blood disorders represented an annual healthcare cost of €159 per 10 citizens.
“Non-malignant blood disorders cost the European economy nearly as much as all blood cancers combined,” said Jose Leal, DPhil, of the University of Oxford in the UK.
“We found wide differences in the cost of treating blood disorders in different countries, likely linked to the significant differences in the access and delivery of care for patients with blood disorders. Our findings suggest there is a need to harmonize care of blood disorders across Europe in a cost-effective way.”
Study may explain how LSCs evade treatment
Image by Robert Paulson
New research suggests leukemia stem cells (LSCs) can “hide” in gonadal adipose tissue (GAT) and transform the tissue so they can survive treatment.
Experiments in a mouse model of chronic myeloid leukemia (CML) showed that LSCs are enriched in GAT.
While there, the LSCs create a microenvironment that supports leukemic growth and resistance to treatment, and expression of the fatty acid transporter CD36 makes LSCs particularly resistant.
Craig Jordan, PhD, of University of Colorado in Aurora, and his colleagues conducted this research and detailed their findings in Cell Stem Cell.
The researchers began by examining cancer cells found in GAT from mice with blast crisis CML. Rather than containing the expected mix of regular leukemia cells and LSCs, the tissue was enriched for LSCs.
And these GAT-resident LSCs used a different energy source than LSCs in the bone marrow microenvironment. The GAT-resident LSCs powered their survival and growth with fatty acids, manufacturing energy by the process of fatty acid oxidization.
In fact, the GAT-resident LSCs actively signaled fat to undergo lipolysis, which released fatty acids into the microenvironment.
“The basic biology was fascinating,” Dr Jordan said. “The tumor adapted the local environment to suit itself.”
Dr Jordan and his colleagues also found that CD36 played a role. CD36+ LSCs were enriched in GAT, were more likely to migrate to GAT than to bone marrow, and were protected from treatment by GAT.
The researchers tested the effects of several drugs (cytarabine, doxorubicin, etoposide, SN-38, irinotecan, and dasatinib) on CD36+ LSCs, CD36- LSCs, and bulk leukemia cells ex vivo.
Both CD36+ and CD36- LSCs were more resistant to treatment than bulk leukemia cells, but CD36+ LSCs were preferentially drug-resistant.
The researchers observed similar results in leukemic mice and found evidence to suggest that CD36 plays a similar role in patients with blast crisis CML and those with acute myeloid leukemia.
Image by Robert Paulson
New research suggests leukemia stem cells (LSCs) can “hide” in gonadal adipose tissue (GAT) and transform the tissue so they can survive treatment.
Experiments in a mouse model of chronic myeloid leukemia (CML) showed that LSCs are enriched in GAT.
While there, the LSCs create a microenvironment that supports leukemic growth and resistance to treatment, and expression of the fatty acid transporter CD36 makes LSCs particularly resistant.
Craig Jordan, PhD, of University of Colorado in Aurora, and his colleagues conducted this research and detailed their findings in Cell Stem Cell.
The researchers began by examining cancer cells found in GAT from mice with blast crisis CML. Rather than containing the expected mix of regular leukemia cells and LSCs, the tissue was enriched for LSCs.
And these GAT-resident LSCs used a different energy source than LSCs in the bone marrow microenvironment. The GAT-resident LSCs powered their survival and growth with fatty acids, manufacturing energy by the process of fatty acid oxidization.
In fact, the GAT-resident LSCs actively signaled fat to undergo lipolysis, which released fatty acids into the microenvironment.
“The basic biology was fascinating,” Dr Jordan said. “The tumor adapted the local environment to suit itself.”
Dr Jordan and his colleagues also found that CD36 played a role. CD36+ LSCs were enriched in GAT, were more likely to migrate to GAT than to bone marrow, and were protected from treatment by GAT.
The researchers tested the effects of several drugs (cytarabine, doxorubicin, etoposide, SN-38, irinotecan, and dasatinib) on CD36+ LSCs, CD36- LSCs, and bulk leukemia cells ex vivo.
Both CD36+ and CD36- LSCs were more resistant to treatment than bulk leukemia cells, but CD36+ LSCs were preferentially drug-resistant.
The researchers observed similar results in leukemic mice and found evidence to suggest that CD36 plays a similar role in patients with blast crisis CML and those with acute myeloid leukemia.
Image by Robert Paulson
New research suggests leukemia stem cells (LSCs) can “hide” in gonadal adipose tissue (GAT) and transform the tissue so they can survive treatment.
Experiments in a mouse model of chronic myeloid leukemia (CML) showed that LSCs are enriched in GAT.
While there, the LSCs create a microenvironment that supports leukemic growth and resistance to treatment, and expression of the fatty acid transporter CD36 makes LSCs particularly resistant.
Craig Jordan, PhD, of University of Colorado in Aurora, and his colleagues conducted this research and detailed their findings in Cell Stem Cell.
The researchers began by examining cancer cells found in GAT from mice with blast crisis CML. Rather than containing the expected mix of regular leukemia cells and LSCs, the tissue was enriched for LSCs.
And these GAT-resident LSCs used a different energy source than LSCs in the bone marrow microenvironment. The GAT-resident LSCs powered their survival and growth with fatty acids, manufacturing energy by the process of fatty acid oxidization.
In fact, the GAT-resident LSCs actively signaled fat to undergo lipolysis, which released fatty acids into the microenvironment.
“The basic biology was fascinating,” Dr Jordan said. “The tumor adapted the local environment to suit itself.”
Dr Jordan and his colleagues also found that CD36 played a role. CD36+ LSCs were enriched in GAT, were more likely to migrate to GAT than to bone marrow, and were protected from treatment by GAT.
The researchers tested the effects of several drugs (cytarabine, doxorubicin, etoposide, SN-38, irinotecan, and dasatinib) on CD36+ LSCs, CD36- LSCs, and bulk leukemia cells ex vivo.
Both CD36+ and CD36- LSCs were more resistant to treatment than bulk leukemia cells, but CD36+ LSCs were preferentially drug-resistant.
The researchers observed similar results in leukemic mice and found evidence to suggest that CD36 plays a similar role in patients with blast crisis CML and those with acute myeloid leukemia.
Ibrutinib approved for first-line treatment of CLL
Photo courtesy of Janssen
Health Canada has approved the Bruton’s tyrosine kinase inhibitor ibrutinib (Imbruvica®) as a first-line treatment for patients with active chronic lymphocytic leukemia (CLL).
This is the fourth approval for ibrutinib in Canada. The drug is now approved for use in all CLL patients, patients with Waldenström’s macroglobulinemia, and patients with relapsed or refractory mantle cell lymphoma (conditional approval).
Ibrutinib is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc.
The latest approval of ibrutinib is based on results from the phase 3 RESONATE-2 trial
(PCYC-1115), which were presented at the 2015 ASH Annual Meeting and
simultaneously published in NEJM.
RESONATE-2 enrolled 269 treatment-naïve patients with CLL or small lymphocytic lymphoma who were 65 or older.
Patients were randomized to receive ibrutinib (n=136) at 420 mg once a day until progression or unacceptable toxicity, or chlorambucil (n=133) on days 1 and 15 of each 28-day cycle for up to 12 cycles. The starting dose for chlorambucil in cycle 1 was 0.5 mg/kg and was increased based on tolerability in cycle 2 by increments of 0.1 mg/kg to a maximum of 0.8 mg/kg.
The primary endpoint of the study was progression-free survival (PFS), as assessed by an independent review committee (IRC) according to the International Workshop on Chronic Lymphocytic Leukemia (iWCLL) 2008 criteria, with modification for treatment-related lymphocytosis.
Key secondary endpoints included overall response rate (based on the same iWCLL criteria), overall survival (OS), and safety.
Ibrutinib significantly prolonged PFS, as determined by the IRC, reducing the risk of progression or death by 84% compared to chlorambucil. The hazard ratio was 0.16 (P<0.001). The median PFS was not reached in the ibrutinib arm but was 18.9 months for the chlorambucil arm.
Ibrutinib significantly prolonged OS as well, although the median OS was not reached in either treatment arm. The OS rate at 24 months was 98% with ibrutinib and 85% with chlorambucil. The relative risk of death with ibrutinib was 84% lower than that with chlorambucil. The hazard ratio was 0.16 (P=0.001).
Ibrutinib was associated with a significantly higher IRC-assessed overall response rate compared to chlorambucil—82% and 35%, respectively (P<0.0001). Five
patients (4%) in the ibrutinib arm achieved a complete response, as did 2 patients (2%) in the chlorambucil arm.
The median duration of treatment was 17.4 months in the ibrutinib arm and 7.1 months in the chlorambucil arm.
The most common adverse events of any grade—in the ibrutinib and chlorambucil arms, respectively—were diarrhea (42% and 17%), fatigue (30% and 38%), cough (22% and 15%), nausea (22% and 39%), peripheral edema (19% and 9%), dry eye (17% and 5%), arthralgia (16% and 7%), neutropenia (16% and 23%), and vomiting (13% and 20%).
Adverse events of grade 3 or higher—in the ibrutinib and chlorambucil arms, respectively—were neutropenia (10% and 18%), anemia (6% and 8%), hypertension (4% and 0%), pneumonia (4% and 2%), diarrhea (4% and 0%), maculopapular rash (3% and 2%), decreased platelet count (3% and 1%), abdominal pain (3% and 1%), hyponatremia (3% and 0%), thrombocytopenia (2% and 6%), febrile neutropenia (2% and 2%), upper respiratory tract infection (2% and 2%), pleural effusion (2% and 1%), cellulitis (2% and 0%), fatigue (1% and 5%), syncope (1% and 2%), and hemolytic anemia (0% and 2%).
Photo courtesy of Janssen
Health Canada has approved the Bruton’s tyrosine kinase inhibitor ibrutinib (Imbruvica®) as a first-line treatment for patients with active chronic lymphocytic leukemia (CLL).
This is the fourth approval for ibrutinib in Canada. The drug is now approved for use in all CLL patients, patients with Waldenström’s macroglobulinemia, and patients with relapsed or refractory mantle cell lymphoma (conditional approval).
Ibrutinib is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc.
The latest approval of ibrutinib is based on results from the phase 3 RESONATE-2 trial
(PCYC-1115), which were presented at the 2015 ASH Annual Meeting and
simultaneously published in NEJM.
RESONATE-2 enrolled 269 treatment-naïve patients with CLL or small lymphocytic lymphoma who were 65 or older.
Patients were randomized to receive ibrutinib (n=136) at 420 mg once a day until progression or unacceptable toxicity, or chlorambucil (n=133) on days 1 and 15 of each 28-day cycle for up to 12 cycles. The starting dose for chlorambucil in cycle 1 was 0.5 mg/kg and was increased based on tolerability in cycle 2 by increments of 0.1 mg/kg to a maximum of 0.8 mg/kg.
The primary endpoint of the study was progression-free survival (PFS), as assessed by an independent review committee (IRC) according to the International Workshop on Chronic Lymphocytic Leukemia (iWCLL) 2008 criteria, with modification for treatment-related lymphocytosis.
Key secondary endpoints included overall response rate (based on the same iWCLL criteria), overall survival (OS), and safety.
Ibrutinib significantly prolonged PFS, as determined by the IRC, reducing the risk of progression or death by 84% compared to chlorambucil. The hazard ratio was 0.16 (P<0.001). The median PFS was not reached in the ibrutinib arm but was 18.9 months for the chlorambucil arm.
Ibrutinib significantly prolonged OS as well, although the median OS was not reached in either treatment arm. The OS rate at 24 months was 98% with ibrutinib and 85% with chlorambucil. The relative risk of death with ibrutinib was 84% lower than that with chlorambucil. The hazard ratio was 0.16 (P=0.001).
Ibrutinib was associated with a significantly higher IRC-assessed overall response rate compared to chlorambucil—82% and 35%, respectively (P<0.0001). Five
patients (4%) in the ibrutinib arm achieved a complete response, as did 2 patients (2%) in the chlorambucil arm.
The median duration of treatment was 17.4 months in the ibrutinib arm and 7.1 months in the chlorambucil arm.
The most common adverse events of any grade—in the ibrutinib and chlorambucil arms, respectively—were diarrhea (42% and 17%), fatigue (30% and 38%), cough (22% and 15%), nausea (22% and 39%), peripheral edema (19% and 9%), dry eye (17% and 5%), arthralgia (16% and 7%), neutropenia (16% and 23%), and vomiting (13% and 20%).
Adverse events of grade 3 or higher—in the ibrutinib and chlorambucil arms, respectively—were neutropenia (10% and 18%), anemia (6% and 8%), hypertension (4% and 0%), pneumonia (4% and 2%), diarrhea (4% and 0%), maculopapular rash (3% and 2%), decreased platelet count (3% and 1%), abdominal pain (3% and 1%), hyponatremia (3% and 0%), thrombocytopenia (2% and 6%), febrile neutropenia (2% and 2%), upper respiratory tract infection (2% and 2%), pleural effusion (2% and 1%), cellulitis (2% and 0%), fatigue (1% and 5%), syncope (1% and 2%), and hemolytic anemia (0% and 2%).
Photo courtesy of Janssen
Health Canada has approved the Bruton’s tyrosine kinase inhibitor ibrutinib (Imbruvica®) as a first-line treatment for patients with active chronic lymphocytic leukemia (CLL).
This is the fourth approval for ibrutinib in Canada. The drug is now approved for use in all CLL patients, patients with Waldenström’s macroglobulinemia, and patients with relapsed or refractory mantle cell lymphoma (conditional approval).
Ibrutinib is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc.
The latest approval of ibrutinib is based on results from the phase 3 RESONATE-2 trial
(PCYC-1115), which were presented at the 2015 ASH Annual Meeting and
simultaneously published in NEJM.
RESONATE-2 enrolled 269 treatment-naïve patients with CLL or small lymphocytic lymphoma who were 65 or older.
Patients were randomized to receive ibrutinib (n=136) at 420 mg once a day until progression or unacceptable toxicity, or chlorambucil (n=133) on days 1 and 15 of each 28-day cycle for up to 12 cycles. The starting dose for chlorambucil in cycle 1 was 0.5 mg/kg and was increased based on tolerability in cycle 2 by increments of 0.1 mg/kg to a maximum of 0.8 mg/kg.
The primary endpoint of the study was progression-free survival (PFS), as assessed by an independent review committee (IRC) according to the International Workshop on Chronic Lymphocytic Leukemia (iWCLL) 2008 criteria, with modification for treatment-related lymphocytosis.
Key secondary endpoints included overall response rate (based on the same iWCLL criteria), overall survival (OS), and safety.
Ibrutinib significantly prolonged PFS, as determined by the IRC, reducing the risk of progression or death by 84% compared to chlorambucil. The hazard ratio was 0.16 (P<0.001). The median PFS was not reached in the ibrutinib arm but was 18.9 months for the chlorambucil arm.
Ibrutinib significantly prolonged OS as well, although the median OS was not reached in either treatment arm. The OS rate at 24 months was 98% with ibrutinib and 85% with chlorambucil. The relative risk of death with ibrutinib was 84% lower than that with chlorambucil. The hazard ratio was 0.16 (P=0.001).
Ibrutinib was associated with a significantly higher IRC-assessed overall response rate compared to chlorambucil—82% and 35%, respectively (P<0.0001). Five
patients (4%) in the ibrutinib arm achieved a complete response, as did 2 patients (2%) in the chlorambucil arm.
The median duration of treatment was 17.4 months in the ibrutinib arm and 7.1 months in the chlorambucil arm.
The most common adverse events of any grade—in the ibrutinib and chlorambucil arms, respectively—were diarrhea (42% and 17%), fatigue (30% and 38%), cough (22% and 15%), nausea (22% and 39%), peripheral edema (19% and 9%), dry eye (17% and 5%), arthralgia (16% and 7%), neutropenia (16% and 23%), and vomiting (13% and 20%).
Adverse events of grade 3 or higher—in the ibrutinib and chlorambucil arms, respectively—were neutropenia (10% and 18%), anemia (6% and 8%), hypertension (4% and 0%), pneumonia (4% and 2%), diarrhea (4% and 0%), maculopapular rash (3% and 2%), decreased platelet count (3% and 1%), abdominal pain (3% and 1%), hyponatremia (3% and 0%), thrombocytopenia (2% and 6%), febrile neutropenia (2% and 2%), upper respiratory tract infection (2% and 2%), pleural effusion (2% and 1%), cellulitis (2% and 0%), fatigue (1% and 5%), syncope (1% and 2%), and hemolytic anemia (0% and 2%).
Radiologists no longer have higher risk of cancer-related death
Photo by Rhoda Baer
Radiologists who graduated from medical school after 1940 do not have an increased risk of dying from radiation-related causes such as cancers, according to a study published in Radiology.
However, the study suggested that male radiologists who graduated before 1940 had a higher risk of death from certain cancers, including acute myeloid leukemia and non-Hodgkin lymphoma.
Researchers said these findings point to the success of efforts to reduce occupational radiation doses over the past several decades.
The team noted that female radiologists did not have an increased risk of all-cause mortality or cancer-related mortality, regardless of when they graduated from medical school.
However, the small number of women in this study prevented the researchers from studying the subjects’ mortality rates in detail. And very few female radiologists worked during the early period of the study, when radiation exposures were likely highest.
To conduct this study, the researchers analyzed records from the American Medical Association Physician Masterfile, a database established in 1906 that has grown to include current and historical data for more than 1.4 million physicians, residents, and medical students in the US.
The team compared cancer incidence and mortality rates between 43,763 radiologists and 64,990 psychiatrists who graduated from medical school between 1916 and 2006. Psychiatrists were chosen as a comparison group because they are unlikely to have had occupational radiation exposure.
“Our most important finding is that radiologists have lower death rates from all causes of death combined, compared to psychiatrists, and had similar risks of cancer deaths overall,” said study author Martha Linet, MD, of the National Cancer Institute in Bethesda, Maryland.
Results in males
The researchers found that, among male subjects who graduated after 1940, the risk of all-cause mortality was lower for the radiologists than the psychiatrists (relative risk [RR]=0.94; 95% CI: 0.90, 0.97), and the risk of death from cancer was similar (RR=1.00; 95% CI: 0.93, 1.07).
In contrast, male radiologists who graduated before 1940 had higher mortality rates from certain cancers.
They had a higher risk of skin cancer mortality (RR=6.38; 95% CI: 1.75, 23.20) that was driven by an excess of melanoma (RR=8.75; 95% CI: 1.89, 40.53).
They had an increased risk of death from all myeloid leukemias (RR=1.43; 95% CI: 1.00, 2.05) that was driven by acute myeloid leukemia and/or myelodysplastic syndromes (RR=4.68; 95% CI: 0.91, 24.18).
And they had an increased risk of death from lymphomas (RR=2.24; 95% CI: 1.31, 3.86) that was driven by non-Hodgkin lymphoma (RR=2.69; 95% CI: 1.33, 5.45).
The researchers also found an increased risk of cerebrovascular deaths in the male radiologists who graduated before 1940 (RR=1.49; 95% CI: 1.11, 2.01).
The team said the reduced health risks for more recent radiology graduates are likely due to developments and improvements in radiation protection and monitoring, along with improvements in equipment safety.
“Most of the findings of increased risk were in the earlier radiologists,” Dr Linet noted. “We do feel there is evidence that decreases in dose in the United States and other countries seem to have paid off, reducing risks in recent graduates.”
Results in females
The researchers said there were no clear increases in mortality in the female radiologists compared with the female psychiatrists.
The risk of all-cause mortality was lower in the radiologists, as was the risk of death from circulatory diseases, but the risk of cancer-related mortality was similar between the radiologists and the psychiatrists.
However, the researchers said the relatively small number of female deaths in this study prevented detailed investigation. Only 2% of female radiologists (208/8851) and 3% of female psychiatrists (524/17,493) died, compared to 12% of male radiologists (4260/43,763) and 16% of male psychiatrists (7815/47,443).
Photo by Rhoda Baer
Radiologists who graduated from medical school after 1940 do not have an increased risk of dying from radiation-related causes such as cancers, according to a study published in Radiology.
However, the study suggested that male radiologists who graduated before 1940 had a higher risk of death from certain cancers, including acute myeloid leukemia and non-Hodgkin lymphoma.
Researchers said these findings point to the success of efforts to reduce occupational radiation doses over the past several decades.
The team noted that female radiologists did not have an increased risk of all-cause mortality or cancer-related mortality, regardless of when they graduated from medical school.
However, the small number of women in this study prevented the researchers from studying the subjects’ mortality rates in detail. And very few female radiologists worked during the early period of the study, when radiation exposures were likely highest.
To conduct this study, the researchers analyzed records from the American Medical Association Physician Masterfile, a database established in 1906 that has grown to include current and historical data for more than 1.4 million physicians, residents, and medical students in the US.
The team compared cancer incidence and mortality rates between 43,763 radiologists and 64,990 psychiatrists who graduated from medical school between 1916 and 2006. Psychiatrists were chosen as a comparison group because they are unlikely to have had occupational radiation exposure.
“Our most important finding is that radiologists have lower death rates from all causes of death combined, compared to psychiatrists, and had similar risks of cancer deaths overall,” said study author Martha Linet, MD, of the National Cancer Institute in Bethesda, Maryland.
Results in males
The researchers found that, among male subjects who graduated after 1940, the risk of all-cause mortality was lower for the radiologists than the psychiatrists (relative risk [RR]=0.94; 95% CI: 0.90, 0.97), and the risk of death from cancer was similar (RR=1.00; 95% CI: 0.93, 1.07).
In contrast, male radiologists who graduated before 1940 had higher mortality rates from certain cancers.
They had a higher risk of skin cancer mortality (RR=6.38; 95% CI: 1.75, 23.20) that was driven by an excess of melanoma (RR=8.75; 95% CI: 1.89, 40.53).
They had an increased risk of death from all myeloid leukemias (RR=1.43; 95% CI: 1.00, 2.05) that was driven by acute myeloid leukemia and/or myelodysplastic syndromes (RR=4.68; 95% CI: 0.91, 24.18).
And they had an increased risk of death from lymphomas (RR=2.24; 95% CI: 1.31, 3.86) that was driven by non-Hodgkin lymphoma (RR=2.69; 95% CI: 1.33, 5.45).
The researchers also found an increased risk of cerebrovascular deaths in the male radiologists who graduated before 1940 (RR=1.49; 95% CI: 1.11, 2.01).
The team said the reduced health risks for more recent radiology graduates are likely due to developments and improvements in radiation protection and monitoring, along with improvements in equipment safety.
“Most of the findings of increased risk were in the earlier radiologists,” Dr Linet noted. “We do feel there is evidence that decreases in dose in the United States and other countries seem to have paid off, reducing risks in recent graduates.”
Results in females
The researchers said there were no clear increases in mortality in the female radiologists compared with the female psychiatrists.
The risk of all-cause mortality was lower in the radiologists, as was the risk of death from circulatory diseases, but the risk of cancer-related mortality was similar between the radiologists and the psychiatrists.
However, the researchers said the relatively small number of female deaths in this study prevented detailed investigation. Only 2% of female radiologists (208/8851) and 3% of female psychiatrists (524/17,493) died, compared to 12% of male radiologists (4260/43,763) and 16% of male psychiatrists (7815/47,443).
Photo by Rhoda Baer
Radiologists who graduated from medical school after 1940 do not have an increased risk of dying from radiation-related causes such as cancers, according to a study published in Radiology.
However, the study suggested that male radiologists who graduated before 1940 had a higher risk of death from certain cancers, including acute myeloid leukemia and non-Hodgkin lymphoma.
Researchers said these findings point to the success of efforts to reduce occupational radiation doses over the past several decades.
The team noted that female radiologists did not have an increased risk of all-cause mortality or cancer-related mortality, regardless of when they graduated from medical school.
However, the small number of women in this study prevented the researchers from studying the subjects’ mortality rates in detail. And very few female radiologists worked during the early period of the study, when radiation exposures were likely highest.
To conduct this study, the researchers analyzed records from the American Medical Association Physician Masterfile, a database established in 1906 that has grown to include current and historical data for more than 1.4 million physicians, residents, and medical students in the US.
The team compared cancer incidence and mortality rates between 43,763 radiologists and 64,990 psychiatrists who graduated from medical school between 1916 and 2006. Psychiatrists were chosen as a comparison group because they are unlikely to have had occupational radiation exposure.
“Our most important finding is that radiologists have lower death rates from all causes of death combined, compared to psychiatrists, and had similar risks of cancer deaths overall,” said study author Martha Linet, MD, of the National Cancer Institute in Bethesda, Maryland.
Results in males
The researchers found that, among male subjects who graduated after 1940, the risk of all-cause mortality was lower for the radiologists than the psychiatrists (relative risk [RR]=0.94; 95% CI: 0.90, 0.97), and the risk of death from cancer was similar (RR=1.00; 95% CI: 0.93, 1.07).
In contrast, male radiologists who graduated before 1940 had higher mortality rates from certain cancers.
They had a higher risk of skin cancer mortality (RR=6.38; 95% CI: 1.75, 23.20) that was driven by an excess of melanoma (RR=8.75; 95% CI: 1.89, 40.53).
They had an increased risk of death from all myeloid leukemias (RR=1.43; 95% CI: 1.00, 2.05) that was driven by acute myeloid leukemia and/or myelodysplastic syndromes (RR=4.68; 95% CI: 0.91, 24.18).
And they had an increased risk of death from lymphomas (RR=2.24; 95% CI: 1.31, 3.86) that was driven by non-Hodgkin lymphoma (RR=2.69; 95% CI: 1.33, 5.45).
The researchers also found an increased risk of cerebrovascular deaths in the male radiologists who graduated before 1940 (RR=1.49; 95% CI: 1.11, 2.01).
The team said the reduced health risks for more recent radiology graduates are likely due to developments and improvements in radiation protection and monitoring, along with improvements in equipment safety.
“Most of the findings of increased risk were in the earlier radiologists,” Dr Linet noted. “We do feel there is evidence that decreases in dose in the United States and other countries seem to have paid off, reducing risks in recent graduates.”
Results in females
The researchers said there were no clear increases in mortality in the female radiologists compared with the female psychiatrists.
The risk of all-cause mortality was lower in the radiologists, as was the risk of death from circulatory diseases, but the risk of cancer-related mortality was similar between the radiologists and the psychiatrists.
However, the researchers said the relatively small number of female deaths in this study prevented detailed investigation. Only 2% of female radiologists (208/8851) and 3% of female psychiatrists (524/17,493) died, compared to 12% of male radiologists (4260/43,763) and 16% of male psychiatrists (7815/47,443).
BTK inhibitor may treat ibrutinib-resistant cancers
Photo by Aaron Logan
KOLOA, HAWAII—Preclinical research suggests that ARQ 531, a reversible Bruton’s tyrosine kinase (BTK) inhibitor, might prove effective against ibrutinib-resistant hematologic malignancies.
The study showed that ARQ 531 inhibits wild-type BTK and the ibrutinib-resistant BTK-C481S mutant with similar potency.
The compound also suppressed proliferation of hematologic cancer cells in vitro and inhibited tumor growth in a mouse model of B-cell lymphoma.
Researchers disclosed these results in a poster presentation at the 2016 Pan Pacific Lymphoma Conference. The research was supported by ArQule Inc., the company developing ARQ 531.
The researchers first demonstrated that ARQ 531 enacts biochemical inhibition of both wild-type and C481S-mutant BTK at sub-nanomolar levels and cellular inhibition in C481S-mutant BTK cells that are resistant to ibrutinib.
The team then tested ARQ 531 in a range of cell lines encompassing a variety of leukemias and lymphomas, as well as multiple myeloma.
They found that ARQ 531 can inhibit proliferation in many types of hematologic cancer cells, but it “potently inhibits” cell lines that are addicted to BCR, PI3K/AKT, and Notch signaling pathways.
The researchers also tested ARQ 531 in the BTK-driven TMD8 xenograft mouse model (B-cell lymphoma). They said the compound demonstrated strong target and pathway inhibition, with sustained tumor growth inhibition.
The team noted that ARQ 531 exhibits a distinct kinase selectivity profile, with strong inhibitory activity against several key oncogenic drivers from TEC, Trk, and Src family kinases. And the compound inhibits the RAF/MEK/ERK and PI3K/AKT/mTOR pathways.
The researchers said these results support further investigation of ARQ 531, particularly in the setting of ibrutinib resistance.
It is currently estimated that about 10% of patients treated with ibrutinib develop resistance, and more than 80% of these patients present with the C481S mutation.
“We are beginning to see increasing resistance to ibrutinib, which is creating the need for a BTK inhibitor, like ARQ 531, that targets the C481S mutation,” said Brian Schwartz, head of research and development and chief medical officer at ArQule.
“The preclinical profile of ARQ 531 as a potent and reversible inhibitor of wild-type and mutant BTK presents the potential for a first-in-class and best-in-class molecule. We are working toward completing GLP [good laboratory practice] toxicology studies and filing an IND [investigational new drug application] in early 2017.”
Photo by Aaron Logan
KOLOA, HAWAII—Preclinical research suggests that ARQ 531, a reversible Bruton’s tyrosine kinase (BTK) inhibitor, might prove effective against ibrutinib-resistant hematologic malignancies.
The study showed that ARQ 531 inhibits wild-type BTK and the ibrutinib-resistant BTK-C481S mutant with similar potency.
The compound also suppressed proliferation of hematologic cancer cells in vitro and inhibited tumor growth in a mouse model of B-cell lymphoma.
Researchers disclosed these results in a poster presentation at the 2016 Pan Pacific Lymphoma Conference. The research was supported by ArQule Inc., the company developing ARQ 531.
The researchers first demonstrated that ARQ 531 enacts biochemical inhibition of both wild-type and C481S-mutant BTK at sub-nanomolar levels and cellular inhibition in C481S-mutant BTK cells that are resistant to ibrutinib.
The team then tested ARQ 531 in a range of cell lines encompassing a variety of leukemias and lymphomas, as well as multiple myeloma.
They found that ARQ 531 can inhibit proliferation in many types of hematologic cancer cells, but it “potently inhibits” cell lines that are addicted to BCR, PI3K/AKT, and Notch signaling pathways.
The researchers also tested ARQ 531 in the BTK-driven TMD8 xenograft mouse model (B-cell lymphoma). They said the compound demonstrated strong target and pathway inhibition, with sustained tumor growth inhibition.
The team noted that ARQ 531 exhibits a distinct kinase selectivity profile, with strong inhibitory activity against several key oncogenic drivers from TEC, Trk, and Src family kinases. And the compound inhibits the RAF/MEK/ERK and PI3K/AKT/mTOR pathways.
The researchers said these results support further investigation of ARQ 531, particularly in the setting of ibrutinib resistance.
It is currently estimated that about 10% of patients treated with ibrutinib develop resistance, and more than 80% of these patients present with the C481S mutation.
“We are beginning to see increasing resistance to ibrutinib, which is creating the need for a BTK inhibitor, like ARQ 531, that targets the C481S mutation,” said Brian Schwartz, head of research and development and chief medical officer at ArQule.
“The preclinical profile of ARQ 531 as a potent and reversible inhibitor of wild-type and mutant BTK presents the potential for a first-in-class and best-in-class molecule. We are working toward completing GLP [good laboratory practice] toxicology studies and filing an IND [investigational new drug application] in early 2017.”
Photo by Aaron Logan
KOLOA, HAWAII—Preclinical research suggests that ARQ 531, a reversible Bruton’s tyrosine kinase (BTK) inhibitor, might prove effective against ibrutinib-resistant hematologic malignancies.
The study showed that ARQ 531 inhibits wild-type BTK and the ibrutinib-resistant BTK-C481S mutant with similar potency.
The compound also suppressed proliferation of hematologic cancer cells in vitro and inhibited tumor growth in a mouse model of B-cell lymphoma.
Researchers disclosed these results in a poster presentation at the 2016 Pan Pacific Lymphoma Conference. The research was supported by ArQule Inc., the company developing ARQ 531.
The researchers first demonstrated that ARQ 531 enacts biochemical inhibition of both wild-type and C481S-mutant BTK at sub-nanomolar levels and cellular inhibition in C481S-mutant BTK cells that are resistant to ibrutinib.
The team then tested ARQ 531 in a range of cell lines encompassing a variety of leukemias and lymphomas, as well as multiple myeloma.
They found that ARQ 531 can inhibit proliferation in many types of hematologic cancer cells, but it “potently inhibits” cell lines that are addicted to BCR, PI3K/AKT, and Notch signaling pathways.
The researchers also tested ARQ 531 in the BTK-driven TMD8 xenograft mouse model (B-cell lymphoma). They said the compound demonstrated strong target and pathway inhibition, with sustained tumor growth inhibition.
The team noted that ARQ 531 exhibits a distinct kinase selectivity profile, with strong inhibitory activity against several key oncogenic drivers from TEC, Trk, and Src family kinases. And the compound inhibits the RAF/MEK/ERK and PI3K/AKT/mTOR pathways.
The researchers said these results support further investigation of ARQ 531, particularly in the setting of ibrutinib resistance.
It is currently estimated that about 10% of patients treated with ibrutinib develop resistance, and more than 80% of these patients present with the C481S mutation.
“We are beginning to see increasing resistance to ibrutinib, which is creating the need for a BTK inhibitor, like ARQ 531, that targets the C481S mutation,” said Brian Schwartz, head of research and development and chief medical officer at ArQule.
“The preclinical profile of ARQ 531 as a potent and reversible inhibitor of wild-type and mutant BTK presents the potential for a first-in-class and best-in-class molecule. We are working toward completing GLP [good laboratory practice] toxicology studies and filing an IND [investigational new drug application] in early 2017.”
FDA rejects pegfilgrastim biosimilar
The US Food and Drug Administration (FDA) has decided not to approve Novartis’s application for a biosimilar of Amgen’s Neulasta, also known by the generic name pegfilgrastim.
The FDA issued a complete response letter for the pegfilgrastim biosimilar last month.
Novartis has not provided details about the agency’s decision or the contents of the letter, but the company said it is working with the FDA to answer its questions about the drug.
Novartis was seeking approval for its pegfilgrastim biosimilar for the same indication as Amgen’s Neulasta.
Neulasta is a leukocyte growth factor that is FDA-approved for the following indications:
- To decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.
- To increase survival in patients acutely exposed to myelosuppressive doses of radiation.
Neulasta is not FDA-approved for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.
The US Food and Drug Administration (FDA) has decided not to approve Novartis’s application for a biosimilar of Amgen’s Neulasta, also known by the generic name pegfilgrastim.
The FDA issued a complete response letter for the pegfilgrastim biosimilar last month.
Novartis has not provided details about the agency’s decision or the contents of the letter, but the company said it is working with the FDA to answer its questions about the drug.
Novartis was seeking approval for its pegfilgrastim biosimilar for the same indication as Amgen’s Neulasta.
Neulasta is a leukocyte growth factor that is FDA-approved for the following indications:
- To decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.
- To increase survival in patients acutely exposed to myelosuppressive doses of radiation.
Neulasta is not FDA-approved for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.
The US Food and Drug Administration (FDA) has decided not to approve Novartis’s application for a biosimilar of Amgen’s Neulasta, also known by the generic name pegfilgrastim.
The FDA issued a complete response letter for the pegfilgrastim biosimilar last month.
Novartis has not provided details about the agency’s decision or the contents of the letter, but the company said it is working with the FDA to answer its questions about the drug.
Novartis was seeking approval for its pegfilgrastim biosimilar for the same indication as Amgen’s Neulasta.
Neulasta is a leukocyte growth factor that is FDA-approved for the following indications:
- To decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.
- To increase survival in patients acutely exposed to myelosuppressive doses of radiation.
Neulasta is not FDA-approved for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.
Antimalarials, antifungals may fight leukemia
A new study has shed light on the process leukemia cells use to evade apoptosis and revealed drugs that can fight this process.
Investigators found that leukemia cells expel a molecule that starts apoptosis, but antimalarial drugs and antifungal drugs can halt this process and force the leukemia cells to self-destruct.
Alexandre Chigaev, PhD, of the University of New Mexico in Albuquerque, and his colleagues described these discoveries in Oncotarget.
The investigators theorized that leukemia cells might evade death by regulating 3’-5’-cyclic adenosine monophosphate (cAMP), which is associated with pro-apoptotic signaling.
The team thought leukemic cells might possess mechanisms that efflux cAMP from the cytoplasm, thereby protecting them from apoptosis.
In studying VLA-4—an adhesion molecule that keeps each cell in its niche—the investigators discovered that cAMP reduces VLA-4’s adhesive properties, allowing cells to detach.
“That’s how we stumbled upon it,” Dr Chigaev said. “Cyclic AMP reduces cell adhesion, and maybe that’s one of the mechanisms by which [leukemic] cells leave bone marrow niches.”
The investigators then confirmed that cAMP starts apoptosis in leukemia cells. And they showed that leukemia cells could efflux cAMP, but normal blood cells could not.
The team substantiated their findings by testing several drugs that block cAMP efflux.
The drugs, which are all approved by the US Food and Drug Administration, are used to fight malaria or fungal infections. They include artesunate, dihydroartemisinin, clioquinol, cryptotanshinone, parthenolide, and patulin.
The investigators found these drugs successfully decreased cAMP efflux and induced apoptosis in a model of acute myeloid leukemia, in B-lineage acute lymphoblastic leukemia cell lines, and in samples from patients with B-lineage acute lymphoblastic leukemia.
On the other hand, the drugs did not affect peripheral blood mononuclear cells.
“This particular mechanism of action has not been reported for these drugs,” Dr Chigaev said. “And the idea that cells can have this apoptotic escape, or apoptotic evasion, through cyclic AMP pumping, that’s new. It’s never been reported previously.”
Dr Chigaev and his colleagues noted that repurposing already-approved drugs could greatly shorten the approval process to use them for leukemia.
Since the drugs were tested on cells from leukemia patients, the team hopes to continue seeing promising results. They have begun animal studies in preparation for clinical trials.
A new study has shed light on the process leukemia cells use to evade apoptosis and revealed drugs that can fight this process.
Investigators found that leukemia cells expel a molecule that starts apoptosis, but antimalarial drugs and antifungal drugs can halt this process and force the leukemia cells to self-destruct.
Alexandre Chigaev, PhD, of the University of New Mexico in Albuquerque, and his colleagues described these discoveries in Oncotarget.
The investigators theorized that leukemia cells might evade death by regulating 3’-5’-cyclic adenosine monophosphate (cAMP), which is associated with pro-apoptotic signaling.
The team thought leukemic cells might possess mechanisms that efflux cAMP from the cytoplasm, thereby protecting them from apoptosis.
In studying VLA-4—an adhesion molecule that keeps each cell in its niche—the investigators discovered that cAMP reduces VLA-4’s adhesive properties, allowing cells to detach.
“That’s how we stumbled upon it,” Dr Chigaev said. “Cyclic AMP reduces cell adhesion, and maybe that’s one of the mechanisms by which [leukemic] cells leave bone marrow niches.”
The investigators then confirmed that cAMP starts apoptosis in leukemia cells. And they showed that leukemia cells could efflux cAMP, but normal blood cells could not.
The team substantiated their findings by testing several drugs that block cAMP efflux.
The drugs, which are all approved by the US Food and Drug Administration, are used to fight malaria or fungal infections. They include artesunate, dihydroartemisinin, clioquinol, cryptotanshinone, parthenolide, and patulin.
The investigators found these drugs successfully decreased cAMP efflux and induced apoptosis in a model of acute myeloid leukemia, in B-lineage acute lymphoblastic leukemia cell lines, and in samples from patients with B-lineage acute lymphoblastic leukemia.
On the other hand, the drugs did not affect peripheral blood mononuclear cells.
“This particular mechanism of action has not been reported for these drugs,” Dr Chigaev said. “And the idea that cells can have this apoptotic escape, or apoptotic evasion, through cyclic AMP pumping, that’s new. It’s never been reported previously.”
Dr Chigaev and his colleagues noted that repurposing already-approved drugs could greatly shorten the approval process to use them for leukemia.
Since the drugs were tested on cells from leukemia patients, the team hopes to continue seeing promising results. They have begun animal studies in preparation for clinical trials.
A new study has shed light on the process leukemia cells use to evade apoptosis and revealed drugs that can fight this process.
Investigators found that leukemia cells expel a molecule that starts apoptosis, but antimalarial drugs and antifungal drugs can halt this process and force the leukemia cells to self-destruct.
Alexandre Chigaev, PhD, of the University of New Mexico in Albuquerque, and his colleagues described these discoveries in Oncotarget.
The investigators theorized that leukemia cells might evade death by regulating 3’-5’-cyclic adenosine monophosphate (cAMP), which is associated with pro-apoptotic signaling.
The team thought leukemic cells might possess mechanisms that efflux cAMP from the cytoplasm, thereby protecting them from apoptosis.
In studying VLA-4—an adhesion molecule that keeps each cell in its niche—the investigators discovered that cAMP reduces VLA-4’s adhesive properties, allowing cells to detach.
“That’s how we stumbled upon it,” Dr Chigaev said. “Cyclic AMP reduces cell adhesion, and maybe that’s one of the mechanisms by which [leukemic] cells leave bone marrow niches.”
The investigators then confirmed that cAMP starts apoptosis in leukemia cells. And they showed that leukemia cells could efflux cAMP, but normal blood cells could not.
The team substantiated their findings by testing several drugs that block cAMP efflux.
The drugs, which are all approved by the US Food and Drug Administration, are used to fight malaria or fungal infections. They include artesunate, dihydroartemisinin, clioquinol, cryptotanshinone, parthenolide, and patulin.
The investigators found these drugs successfully decreased cAMP efflux and induced apoptosis in a model of acute myeloid leukemia, in B-lineage acute lymphoblastic leukemia cell lines, and in samples from patients with B-lineage acute lymphoblastic leukemia.
On the other hand, the drugs did not affect peripheral blood mononuclear cells.
“This particular mechanism of action has not been reported for these drugs,” Dr Chigaev said. “And the idea that cells can have this apoptotic escape, or apoptotic evasion, through cyclic AMP pumping, that’s new. It’s never been reported previously.”
Dr Chigaev and his colleagues noted that repurposing already-approved drugs could greatly shorten the approval process to use them for leukemia.
Since the drugs were tested on cells from leukemia patients, the team hopes to continue seeing promising results. They have begun animal studies in preparation for clinical trials.
Cancer patients and docs disagree about prognosis
patient and her father
Photo by Rhoda Baer
In a survey of advanced cancer patients and their oncologists, differing opinions about prognosis were common.
And the vast majority of patients didn’t know their doctors held different opinions about how long the patients might live.
Results of the survey were published in JAMA Oncology.
“We’ve discovered 2 important things happening between oncologists and patients with advanced cancer,” said study author Ronald M. Epstein, MD, of the University of Rochester Medical Center in Rochester, New York.
“First, some patients might know the doctor’s prognosis estimate, but the patient chooses to disagree, often because they believe other sources. And, second, some patients think that their doctor agrees with their opinion about prognosis but, in fact, the doctor doesn’t.”
Dr Epstein and his colleagues surveyed 236 patients with stage 3 or 4 cancer. According to medical evidence, fewer than 5% of these patients would be expected to live for 5 years.
The 38 oncologists who treated these patients were also surveyed. The doctors were asked,“What do you believe are the chances that this patient will live for 2 years or more?” And the patients were asked, “What do you believe are the chances that you will live for 2 years or more?”
Additional survey questions gauged whether patients knew their prognosis opinions differed from their doctors and to what extent treatment options were discussed in the context of life expectancy.
Among the 236 patients, 68% rated their survival prognosis differently than their oncologists, and 89% of these patients did not realize their opinions differed from their oncologists. In nearly all cases (96%), the patients were more optimistic than their doctors.
“Of course, it’s only possible for doctors to provide a ball-park estimate about life expectancy, and some people do beat the odds,” Dr Epstein noted. “But when a patient with very advanced cancer says that he has a 90% to 100% chance of being alive in 2 years and his oncologist believes that chance is more like 10%, there’s a problem.”
The challenge, according to Dr Epstein and his colleagues, is that talking about a cancer prognosis is not a straightforward exchange of information. It occurs in the context of fear, confusion, and uncertainty.
The researchers said prognosis should be addressed in several conversations about personal values and treatment goals. When doctor-patient communication is poor, it can result in mutual regret about end-of-life circumstances.
For example, nearly all of the patients surveyed said they wanted to be involved in treatment decisions. And 70% said they preferred supportive care at the end of their lives as opposed to aggressive therapy. However, as the researchers pointed out, making an informed decision requires knowing when death is approaching.
“When people think they’ll live a very long time with cancer, despite evidence to the contrary, they may end up taking more aggressive chemotherapy and agreeing to be placed on ventilators or dialysis, paradoxically reducing their quality of life, keeping them from enjoying time with family, and sometimes even shortening their lives,” Dr Epstein said. “So it’s very important for doctors and patients to be on the same page.”
patient and her father
Photo by Rhoda Baer
In a survey of advanced cancer patients and their oncologists, differing opinions about prognosis were common.
And the vast majority of patients didn’t know their doctors held different opinions about how long the patients might live.
Results of the survey were published in JAMA Oncology.
“We’ve discovered 2 important things happening between oncologists and patients with advanced cancer,” said study author Ronald M. Epstein, MD, of the University of Rochester Medical Center in Rochester, New York.
“First, some patients might know the doctor’s prognosis estimate, but the patient chooses to disagree, often because they believe other sources. And, second, some patients think that their doctor agrees with their opinion about prognosis but, in fact, the doctor doesn’t.”
Dr Epstein and his colleagues surveyed 236 patients with stage 3 or 4 cancer. According to medical evidence, fewer than 5% of these patients would be expected to live for 5 years.
The 38 oncologists who treated these patients were also surveyed. The doctors were asked,“What do you believe are the chances that this patient will live for 2 years or more?” And the patients were asked, “What do you believe are the chances that you will live for 2 years or more?”
Additional survey questions gauged whether patients knew their prognosis opinions differed from their doctors and to what extent treatment options were discussed in the context of life expectancy.
Among the 236 patients, 68% rated their survival prognosis differently than their oncologists, and 89% of these patients did not realize their opinions differed from their oncologists. In nearly all cases (96%), the patients were more optimistic than their doctors.
“Of course, it’s only possible for doctors to provide a ball-park estimate about life expectancy, and some people do beat the odds,” Dr Epstein noted. “But when a patient with very advanced cancer says that he has a 90% to 100% chance of being alive in 2 years and his oncologist believes that chance is more like 10%, there’s a problem.”
The challenge, according to Dr Epstein and his colleagues, is that talking about a cancer prognosis is not a straightforward exchange of information. It occurs in the context of fear, confusion, and uncertainty.
The researchers said prognosis should be addressed in several conversations about personal values and treatment goals. When doctor-patient communication is poor, it can result in mutual regret about end-of-life circumstances.
For example, nearly all of the patients surveyed said they wanted to be involved in treatment decisions. And 70% said they preferred supportive care at the end of their lives as opposed to aggressive therapy. However, as the researchers pointed out, making an informed decision requires knowing when death is approaching.
“When people think they’ll live a very long time with cancer, despite evidence to the contrary, they may end up taking more aggressive chemotherapy and agreeing to be placed on ventilators or dialysis, paradoxically reducing their quality of life, keeping them from enjoying time with family, and sometimes even shortening their lives,” Dr Epstein said. “So it’s very important for doctors and patients to be on the same page.”
patient and her father
Photo by Rhoda Baer
In a survey of advanced cancer patients and their oncologists, differing opinions about prognosis were common.
And the vast majority of patients didn’t know their doctors held different opinions about how long the patients might live.
Results of the survey were published in JAMA Oncology.
“We’ve discovered 2 important things happening between oncologists and patients with advanced cancer,” said study author Ronald M. Epstein, MD, of the University of Rochester Medical Center in Rochester, New York.
“First, some patients might know the doctor’s prognosis estimate, but the patient chooses to disagree, often because they believe other sources. And, second, some patients think that their doctor agrees with their opinion about prognosis but, in fact, the doctor doesn’t.”
Dr Epstein and his colleagues surveyed 236 patients with stage 3 or 4 cancer. According to medical evidence, fewer than 5% of these patients would be expected to live for 5 years.
The 38 oncologists who treated these patients were also surveyed. The doctors were asked,“What do you believe are the chances that this patient will live for 2 years or more?” And the patients were asked, “What do you believe are the chances that you will live for 2 years or more?”
Additional survey questions gauged whether patients knew their prognosis opinions differed from their doctors and to what extent treatment options were discussed in the context of life expectancy.
Among the 236 patients, 68% rated their survival prognosis differently than their oncologists, and 89% of these patients did not realize their opinions differed from their oncologists. In nearly all cases (96%), the patients were more optimistic than their doctors.
“Of course, it’s only possible for doctors to provide a ball-park estimate about life expectancy, and some people do beat the odds,” Dr Epstein noted. “But when a patient with very advanced cancer says that he has a 90% to 100% chance of being alive in 2 years and his oncologist believes that chance is more like 10%, there’s a problem.”
The challenge, according to Dr Epstein and his colleagues, is that talking about a cancer prognosis is not a straightforward exchange of information. It occurs in the context of fear, confusion, and uncertainty.
The researchers said prognosis should be addressed in several conversations about personal values and treatment goals. When doctor-patient communication is poor, it can result in mutual regret about end-of-life circumstances.
For example, nearly all of the patients surveyed said they wanted to be involved in treatment decisions. And 70% said they preferred supportive care at the end of their lives as opposed to aggressive therapy. However, as the researchers pointed out, making an informed decision requires knowing when death is approaching.
“When people think they’ll live a very long time with cancer, despite evidence to the contrary, they may end up taking more aggressive chemotherapy and agreeing to be placed on ventilators or dialysis, paradoxically reducing their quality of life, keeping them from enjoying time with family, and sometimes even shortening their lives,” Dr Epstein said. “So it’s very important for doctors and patients to be on the same page.”
Weight loss lowers levels of cancer-associated proteins
A study of more than 400 women suggests that losing weight can reduce levels of cancer-promoting proteins in the blood.
Overweight or obese women who lost weight over a 12-month period—through diet alone or both diet and exercise—significantly lowered their levels of proteins that play a role in angiogenesis.
Researchers say this finding suggests that losing weight might help reduce the risk of developing certain cancers.
“We know that being overweight and having a sedentary lifestyle is associated with an increase in risk for developing certain types of cancer,” said Catherine Duggan, PhD, of the Fred Hutchinson Cancer Research Center in Seattle, Washington.
“However, we don’t know exactly why. We wanted to investigate how levels of some biomarkers associated with angiogenesis were altered when overweight, sedentary, postmenopausal women enrolled in a research study lost weight and/or became physically active over the course of a year.”
Dr Duggan and her colleagues described this investigation in Cancer Research.
The team studied 439 women who were postmenopausal and overweight or obese but were otherwise healthy and ranged in age from 50 to 75.
The women were randomized to 1 of 4 study arms:
- A diet arm, in which women restricted their calorie intake to no more than 2000 kcal per day that included less than 30% of fat calories
- An aerobic exercise arm, in which women performed 45 minutes of moderate to vigorous exercise 5 days a week
- A combined diet and exercise arm
- A control arm.
The researchers collected blood samples at baseline and at 12 months, measuring levels of the angiogenesis-related proteins VEGF, PAI-1, and PEDF.
They also measured weight loss at 12 months and found that women in all 3 intervention arms had a significantly higher mean weight loss than women in the control arm.
The mean weight loss was 0.8% of body weight for women in the control arm, 2.4% for women in the exercise arm (P=0.03), 8.5% for women in the diet arm (P<0.001), and 10.8% for women in the diet and exercise arm (P<0.001).
Compared with women in the control arm, those in the diet-only arm and the diet and exercise arm had significantly lower levels of the angiogenesis-related proteins at 12 months. However, such effects were not apparent among women in the exercise-only arm.
Specifically, women in the diet and exercise arm had a significantly greater reduction in PAI-1 at 12 months than women in the control arm (-19.3% and +3.48%, respectively, P<0.0001).
Women in the diet-only arm and the diet and exercise arm had significantly greater reductions in PEDF than controls (-9.20%, -9.90%, and +0.18%, respectively, both P<0.0001).
And women in the diet-only arm (-8.25%, P=0.0005) and the diet and exercise arm (-9.98%, P<0.0001) had significantly greater reductions in VEGF than controls (-1.21%).
The researchers also observed a linear trend in the reductions. So the more weight loss the women experienced, the greater the reduction in angiogenesis-related protein levels.
“Our study shows that weight loss is a safe and effective method of improving the angiogenic profile in healthy individuals,” Dr Duggan said. “We were surprised by the magnitude of change in these biomarkers with weight loss.”
“While we can’t say for certain that reducing the circulating levels of angiogenic factors through weight loss would impact the growth of tumors, it is possible that they might be associated with a less favorable milieu for tumor growth and proliferation.”
Dr Duggan and her colleagues said limitations of this study include the fact that the researchers only measured 3 angiogenic factors and did not measure them in adipose or other tissues.
A study of more than 400 women suggests that losing weight can reduce levels of cancer-promoting proteins in the blood.
Overweight or obese women who lost weight over a 12-month period—through diet alone or both diet and exercise—significantly lowered their levels of proteins that play a role in angiogenesis.
Researchers say this finding suggests that losing weight might help reduce the risk of developing certain cancers.
“We know that being overweight and having a sedentary lifestyle is associated with an increase in risk for developing certain types of cancer,” said Catherine Duggan, PhD, of the Fred Hutchinson Cancer Research Center in Seattle, Washington.
“However, we don’t know exactly why. We wanted to investigate how levels of some biomarkers associated with angiogenesis were altered when overweight, sedentary, postmenopausal women enrolled in a research study lost weight and/or became physically active over the course of a year.”
Dr Duggan and her colleagues described this investigation in Cancer Research.
The team studied 439 women who were postmenopausal and overweight or obese but were otherwise healthy and ranged in age from 50 to 75.
The women were randomized to 1 of 4 study arms:
- A diet arm, in which women restricted their calorie intake to no more than 2000 kcal per day that included less than 30% of fat calories
- An aerobic exercise arm, in which women performed 45 minutes of moderate to vigorous exercise 5 days a week
- A combined diet and exercise arm
- A control arm.
The researchers collected blood samples at baseline and at 12 months, measuring levels of the angiogenesis-related proteins VEGF, PAI-1, and PEDF.
They also measured weight loss at 12 months and found that women in all 3 intervention arms had a significantly higher mean weight loss than women in the control arm.
The mean weight loss was 0.8% of body weight for women in the control arm, 2.4% for women in the exercise arm (P=0.03), 8.5% for women in the diet arm (P<0.001), and 10.8% for women in the diet and exercise arm (P<0.001).
Compared with women in the control arm, those in the diet-only arm and the diet and exercise arm had significantly lower levels of the angiogenesis-related proteins at 12 months. However, such effects were not apparent among women in the exercise-only arm.
Specifically, women in the diet and exercise arm had a significantly greater reduction in PAI-1 at 12 months than women in the control arm (-19.3% and +3.48%, respectively, P<0.0001).
Women in the diet-only arm and the diet and exercise arm had significantly greater reductions in PEDF than controls (-9.20%, -9.90%, and +0.18%, respectively, both P<0.0001).
And women in the diet-only arm (-8.25%, P=0.0005) and the diet and exercise arm (-9.98%, P<0.0001) had significantly greater reductions in VEGF than controls (-1.21%).
The researchers also observed a linear trend in the reductions. So the more weight loss the women experienced, the greater the reduction in angiogenesis-related protein levels.
“Our study shows that weight loss is a safe and effective method of improving the angiogenic profile in healthy individuals,” Dr Duggan said. “We were surprised by the magnitude of change in these biomarkers with weight loss.”
“While we can’t say for certain that reducing the circulating levels of angiogenic factors through weight loss would impact the growth of tumors, it is possible that they might be associated with a less favorable milieu for tumor growth and proliferation.”
Dr Duggan and her colleagues said limitations of this study include the fact that the researchers only measured 3 angiogenic factors and did not measure them in adipose or other tissues.
A study of more than 400 women suggests that losing weight can reduce levels of cancer-promoting proteins in the blood.
Overweight or obese women who lost weight over a 12-month period—through diet alone or both diet and exercise—significantly lowered their levels of proteins that play a role in angiogenesis.
Researchers say this finding suggests that losing weight might help reduce the risk of developing certain cancers.
“We know that being overweight and having a sedentary lifestyle is associated with an increase in risk for developing certain types of cancer,” said Catherine Duggan, PhD, of the Fred Hutchinson Cancer Research Center in Seattle, Washington.
“However, we don’t know exactly why. We wanted to investigate how levels of some biomarkers associated with angiogenesis were altered when overweight, sedentary, postmenopausal women enrolled in a research study lost weight and/or became physically active over the course of a year.”
Dr Duggan and her colleagues described this investigation in Cancer Research.
The team studied 439 women who were postmenopausal and overweight or obese but were otherwise healthy and ranged in age from 50 to 75.
The women were randomized to 1 of 4 study arms:
- A diet arm, in which women restricted their calorie intake to no more than 2000 kcal per day that included less than 30% of fat calories
- An aerobic exercise arm, in which women performed 45 minutes of moderate to vigorous exercise 5 days a week
- A combined diet and exercise arm
- A control arm.
The researchers collected blood samples at baseline and at 12 months, measuring levels of the angiogenesis-related proteins VEGF, PAI-1, and PEDF.
They also measured weight loss at 12 months and found that women in all 3 intervention arms had a significantly higher mean weight loss than women in the control arm.
The mean weight loss was 0.8% of body weight for women in the control arm, 2.4% for women in the exercise arm (P=0.03), 8.5% for women in the diet arm (P<0.001), and 10.8% for women in the diet and exercise arm (P<0.001).
Compared with women in the control arm, those in the diet-only arm and the diet and exercise arm had significantly lower levels of the angiogenesis-related proteins at 12 months. However, such effects were not apparent among women in the exercise-only arm.
Specifically, women in the diet and exercise arm had a significantly greater reduction in PAI-1 at 12 months than women in the control arm (-19.3% and +3.48%, respectively, P<0.0001).
Women in the diet-only arm and the diet and exercise arm had significantly greater reductions in PEDF than controls (-9.20%, -9.90%, and +0.18%, respectively, both P<0.0001).
And women in the diet-only arm (-8.25%, P=0.0005) and the diet and exercise arm (-9.98%, P<0.0001) had significantly greater reductions in VEGF than controls (-1.21%).
The researchers also observed a linear trend in the reductions. So the more weight loss the women experienced, the greater the reduction in angiogenesis-related protein levels.
“Our study shows that weight loss is a safe and effective method of improving the angiogenic profile in healthy individuals,” Dr Duggan said. “We were surprised by the magnitude of change in these biomarkers with weight loss.”
“While we can’t say for certain that reducing the circulating levels of angiogenic factors through weight loss would impact the growth of tumors, it is possible that they might be associated with a less favorable milieu for tumor growth and proliferation.”
Dr Duggan and her colleagues said limitations of this study include the fact that the researchers only measured 3 angiogenic factors and did not measure them in adipose or other tissues.
Predicting outcomes in AML patients
Photo by Darren Baker
An international competition has produced models that can help predict outcomes in patients with acute myeloid leukemia (AML), according to researchers.
For the competition, known as the DREAM 9 challenge, 31 teams of computational researchers attempted to predict outcomes using data from hundreds of patients with AML.
DREAM, which stands for Dialogue for Reverse Engineering Assessment and Methods, is a platform for crowd-sourced studies that focus on developing computational tools to solve biomedical problems.
Essentially, it’s a competition that serves as a large, long-standing, international scientific collaboration.
“We used DREAM as a way to get general insight into making more accurate predictive models of clinical outcomes,” said Amina Qutub, PhD, of Rice University in Houston, Texas.
She and her colleagues described this effort in PLOS Computational Biology.
For the DREAM 9 challenge, each team was presented with training data from 191 AML patients, which included demographic information, such as age and gender, and more complex proteomic and phosphoprotein data that describes signaling protein pathways believed to play a role in AML.
The teams were also presented with a test set of 100 AML patients and were asked to predict response to therapy, remission duration, or overall survival for these patients.
The top-performing models—by Team EvoMed of Arizona State University and Team Chipmunks of the Ontario Institute for Cancer Research—were able to predict patient response to therapy with an accuracy of close to 80%.
Both of these models were impacted by the perturbation of PIK3CA and NPM1, which singles out these proteins as candidates for further study, according to researchers.
Another discovery resulting from this competition was that, overall, the 31 models were not as effective for predicting outcomes in patients classified as “resistant to therapy” than for responsive patients.
The median model prediction accuracy was 42% for resistant patients and 73% for responsive patients.
Photo by Darren Baker
An international competition has produced models that can help predict outcomes in patients with acute myeloid leukemia (AML), according to researchers.
For the competition, known as the DREAM 9 challenge, 31 teams of computational researchers attempted to predict outcomes using data from hundreds of patients with AML.
DREAM, which stands for Dialogue for Reverse Engineering Assessment and Methods, is a platform for crowd-sourced studies that focus on developing computational tools to solve biomedical problems.
Essentially, it’s a competition that serves as a large, long-standing, international scientific collaboration.
“We used DREAM as a way to get general insight into making more accurate predictive models of clinical outcomes,” said Amina Qutub, PhD, of Rice University in Houston, Texas.
She and her colleagues described this effort in PLOS Computational Biology.
For the DREAM 9 challenge, each team was presented with training data from 191 AML patients, which included demographic information, such as age and gender, and more complex proteomic and phosphoprotein data that describes signaling protein pathways believed to play a role in AML.
The teams were also presented with a test set of 100 AML patients and were asked to predict response to therapy, remission duration, or overall survival for these patients.
The top-performing models—by Team EvoMed of Arizona State University and Team Chipmunks of the Ontario Institute for Cancer Research—were able to predict patient response to therapy with an accuracy of close to 80%.
Both of these models were impacted by the perturbation of PIK3CA and NPM1, which singles out these proteins as candidates for further study, according to researchers.
Another discovery resulting from this competition was that, overall, the 31 models were not as effective for predicting outcomes in patients classified as “resistant to therapy” than for responsive patients.
The median model prediction accuracy was 42% for resistant patients and 73% for responsive patients.
Photo by Darren Baker
An international competition has produced models that can help predict outcomes in patients with acute myeloid leukemia (AML), according to researchers.
For the competition, known as the DREAM 9 challenge, 31 teams of computational researchers attempted to predict outcomes using data from hundreds of patients with AML.
DREAM, which stands for Dialogue for Reverse Engineering Assessment and Methods, is a platform for crowd-sourced studies that focus on developing computational tools to solve biomedical problems.
Essentially, it’s a competition that serves as a large, long-standing, international scientific collaboration.
“We used DREAM as a way to get general insight into making more accurate predictive models of clinical outcomes,” said Amina Qutub, PhD, of Rice University in Houston, Texas.
She and her colleagues described this effort in PLOS Computational Biology.
For the DREAM 9 challenge, each team was presented with training data from 191 AML patients, which included demographic information, such as age and gender, and more complex proteomic and phosphoprotein data that describes signaling protein pathways believed to play a role in AML.
The teams were also presented with a test set of 100 AML patients and were asked to predict response to therapy, remission duration, or overall survival for these patients.
The top-performing models—by Team EvoMed of Arizona State University and Team Chipmunks of the Ontario Institute for Cancer Research—were able to predict patient response to therapy with an accuracy of close to 80%.
Both of these models were impacted by the perturbation of PIK3CA and NPM1, which singles out these proteins as candidates for further study, according to researchers.
Another discovery resulting from this competition was that, overall, the 31 models were not as effective for predicting outcomes in patients classified as “resistant to therapy” than for responsive patients.
The median model prediction accuracy was 42% for resistant patients and 73% for responsive patients.