Lymphoma & Plasma Cell Disorders

Fish oil capsules

Consuming certain types of fish and taking fish oil supplements may induce chemoresistance, according to research published in JAMA Oncology.

Researchers found that herring and mackerel, as well as 6 different types of fish oil supplements, raised blood levels of the fatty acid 16:4(n-3).

And experiments in mice showed that small amounts of either purified 16:4(n-3) or fish oil induced resistance to the chemotherapy drug cisplatin.

Emile E. Voest, MD, PhD, of the Netherlands Cancer Institute in Amsterdam, and his colleagues conducted this multi-part study.

In one part, the team conducted a survey to determine the rate of fish oil use among patients undergoing cancer treatment (n=118). Thirty-five patients (30%) reported regular use of nutritional supplements, and 13 (11%) said they used supplements containing omega-3 fatty acids.

For another part of the study, the researchers evaluated 6 types of fish oil supplements. All of them contained relevant amounts of 16:4(n-3), ranging from 0.2 µM to 5.7 µM.

The team also recruited healthy volunteers to examine blood levels of 16:4(n-3) after the ingestion of fish oil supplements (n=30) and fish (n=20).

Volunteers had increased blood levels of 16:4(n-3) after the recommended daily amount of 10 mL of fish oil and after a 50 mL dose. Subjects had an almost-complete normalization of blood levels 8 hours after a 10 mL fish oil dose, but they had a more prolonged elevation of fatty acid levels after a 50 mL dose.

Eating 100 grams of herring and mackerel also increased blood levels of 16:4(n-3) compared with tuna, which did not affect blood levels, and salmon,

which resulted in a small, short-lived peak.

Finally, experiments in mice showed that as little as 2.5 pmol of purified 16:4(n-3) or 1 µL of fish oil was sufficient to induce resistance to the chemotherapy drug cisplatin.

The fish oil/cisplatin combination had no significant impact on mouse tumors when compared to vehicle control treatment. The estimated tumor volume difference was 44.1 mm³ (P >0.99).

When the researchers compared cisplatin alone to cisplatin plus 16:4(n-3), the estimated tumor volume difference was 95.5 mm³ (P=0 .04). When they compared vehicle control to cisplatin alone, there was an estimated tumor volume difference of 142.4 mm³ (P=0.001).

The team said these results suggest that simultaneous exposure to chemotherapy and fish oil may be detrimental to cancer patients. So until further data become available, patients should avoid consuming fish oil from the day before chemotherapy until the day after.

Fish oil capsules

Consuming certain types of fish and taking fish oil supplements may induce chemoresistance, according to research published in JAMA Oncology.

Researchers found that herring and mackerel, as well as 6 different types of fish oil supplements, raised blood levels of the fatty acid 16:4(n-3).

And experiments in mice showed that small amounts of either purified 16:4(n-3) or fish oil induced resistance to the chemotherapy drug cisplatin.

Emile E. Voest, MD, PhD, of the Netherlands Cancer Institute in Amsterdam, and his colleagues conducted this multi-part study.

In one part, the team conducted a survey to determine the rate of fish oil use among patients undergoing cancer treatment (n=118). Thirty-five patients (30%) reported regular use of nutritional supplements, and 13 (11%) said they used supplements containing omega-3 fatty acids.

For another part of the study, the researchers evaluated 6 types of fish oil supplements. All of them contained relevant amounts of 16:4(n-3), ranging from 0.2 µM to 5.7 µM.

The team also recruited healthy volunteers to examine blood levels of 16:4(n-3) after the ingestion of fish oil supplements (n=30) and fish (n=20).

Volunteers had increased blood levels of 16:4(n-3) after the recommended daily amount of 10 mL of fish oil and after a 50 mL dose. Subjects had an almost-complete normalization of blood levels 8 hours after a 10 mL fish oil dose, but they had a more prolonged elevation of fatty acid levels after a 50 mL dose.

Eating 100 grams of herring and mackerel also increased blood levels of 16:4(n-3) compared with tuna, which did not affect blood levels, and salmon,

which resulted in a small, short-lived peak.

Finally, experiments in mice showed that as little as 2.5 pmol of purified 16:4(n-3) or 1 µL of fish oil was sufficient to induce resistance to the chemotherapy drug cisplatin.

The fish oil/cisplatin combination had no significant impact on mouse tumors when compared to vehicle control treatment. The estimated tumor volume difference was 44.1 mm³ (P >0.99).

When the researchers compared cisplatin alone to cisplatin plus 16:4(n-3), the estimated tumor volume difference was 95.5 mm³ (P=0 .04). When they compared vehicle control to cisplatin alone, there was an estimated tumor volume difference of 142.4 mm³ (P=0.001).

The team said these results suggest that simultaneous exposure to chemotherapy and fish oil may be detrimental to cancer patients. So until further data become available, patients should avoid consuming fish oil from the day before chemotherapy until the day after.

Fish oil capsules

Consuming certain types of fish and taking fish oil supplements may induce chemoresistance, according to research published in JAMA Oncology.

Researchers found that herring and mackerel, as well as 6 different types of fish oil supplements, raised blood levels of the fatty acid 16:4(n-3).

And experiments in mice showed that small amounts of either purified 16:4(n-3) or fish oil induced resistance to the chemotherapy drug cisplatin.

Emile E. Voest, MD, PhD, of the Netherlands Cancer Institute in Amsterdam, and his colleagues conducted this multi-part study.

In one part, the team conducted a survey to determine the rate of fish oil use among patients undergoing cancer treatment (n=118). Thirty-five patients (30%) reported regular use of nutritional supplements, and 13 (11%) said they used supplements containing omega-3 fatty acids.

For another part of the study, the researchers evaluated 6 types of fish oil supplements. All of them contained relevant amounts of 16:4(n-3), ranging from 0.2 µM to 5.7 µM.

The team also recruited healthy volunteers to examine blood levels of 16:4(n-3) after the ingestion of fish oil supplements (n=30) and fish (n=20).

Volunteers had increased blood levels of 16:4(n-3) after the recommended daily amount of 10 mL of fish oil and after a 50 mL dose. Subjects had an almost-complete normalization of blood levels 8 hours after a 10 mL fish oil dose, but they had a more prolonged elevation of fatty acid levels after a 50 mL dose.

Eating 100 grams of herring and mackerel also increased blood levels of 16:4(n-3) compared with tuna, which did not affect blood levels, and salmon,

which resulted in a small, short-lived peak.

Finally, experiments in mice showed that as little as 2.5 pmol of purified 16:4(n-3) or 1 µL of fish oil was sufficient to induce resistance to the chemotherapy drug cisplatin.

The fish oil/cisplatin combination had no significant impact on mouse tumors when compared to vehicle control treatment. The estimated tumor volume difference was 44.1 mm³ (P >0.99).

When the researchers compared cisplatin alone to cisplatin plus 16:4(n-3), the estimated tumor volume difference was 95.5 mm³ (P=0 .04). When they compared vehicle control to cisplatin alone, there was an estimated tumor volume difference of 142.4 mm³ (P=0.001).

The team said these results suggest that simultaneous exposure to chemotherapy and fish oil may be detrimental to cancer patients. So until further data become available, patients should avoid consuming fish oil from the day before chemotherapy until the day after.

Wyndham Wilson, MD, PhD

Photo by Larry Young

Surveillance of circulating tumor DNA (ctDNA) can help predict relapse in most patients with diffuse large B-cell lymphoma before there is clinical evidence of the disease, according to a study published in The Lancet Oncology.

Investigators analyzed ctDNA using the clonoSEQ minimal residual disease (MRD) test and found they could predict relapse with a positive predictive value (PPV) of 88% and a negative predictive value (NPV) of 98%.

The test detected relapse a median of 3.5 months quicker than computed tomography (CT) scans.

“Patients with DLBCL with low amounts of disease at relapse have better survival than those with more disease, which is the rationale for surveillance CT scans,” said study author Wyndham Wilson, MD, PhD, of the National Cancer Institute in Bethesda, Maryland.

“Because the ctDNA test detects disease at a molecular level, it detects microscopic disease, which cannot be detected by CT scans, and may improve patient survival. Furthermore, ctDNA is non-invasive and can be employed as frequently needed, unlike surveillance CT scans, which expose patients to radiation and intravenous contrast.”

For this study, Dr Wilson and his colleagues evaluated 126 DLBCL patients who had participated in clinical trials from May 1993 to June 2013 and were followed for a median of 11 years post-treatment.

Surveillance monitoring

To investigate whether ctDNA monitoring could overcome the limitations of standard imaging techniques, the researchers compared serial ctDNA samples to CT scans taken at the same time post-treatment in patients who had achieved complete remission. This was known as “surveillance monitoring.”

The investigators performed surveillance monitoring of ctDNA in 107 patients who achieved complete remission.

The hazard ratio for clinical disease progression was 228 for patients who had detectable ctDNA during surveillance, when compared to patients with undetectable ctDNA (P<0.0001).

Surveillance ctDNA had a PPV of 88.2% and an NPV of 97.8%. And it revealed the risk of recurrence at a median of 3.5 months (range, 0-200 months) before there was evidence of clinical disease.

Interim monitoring

The researchers also analyzed whether the presence of ctDNA at the beginning of the third cycle of treatment predicted relapse, regardless of whether patients achieved complete remission by the end of treatment. This was known as “interim monitoring.”

Of the 108 patients included in the interim monitoring analysis, ctDNA was detected in 24 patients, 15 of whom eventually relapsed. Only 17 of the 84 patients with undetectable interim ctDNA relapsed.

Five years after the interim serum samples were taken, 80.2% of the patients who were negative for ctDNA were relapse-free, as were 41.7% of patients who were positive for ctDNA (P<0.0001).

Detectable interim ctDNA had a PPV of 62.5% and an NPV of 79.8%.

Fourteen of the 15 patients with detectable ctDNA who relapsed did so within 6 months of the end of treatment, as did 7 of the 17 patients without interim ctDNA.

Based on these results, the investigators concluded that surveillance monitoring of ctDNA identifies DLBCL patients at risk of disease recurrence before clinical evidence of disease in most patients, and interim monitoring of ctDNA is a promising biomarker to identify patients at high risk of treatment failure.

This research was funded by Adaptive Biotechnologies, the company developing the clonoSEQ MRD test, as well as the National Cancer Institute.

Wyndham Wilson, MD, PhD

Photo by Larry Young

Surveillance of circulating tumor DNA (ctDNA) can help predict relapse in most patients with diffuse large B-cell lymphoma before there is clinical evidence of the disease, according to a study published in The Lancet Oncology.

Investigators analyzed ctDNA using the clonoSEQ minimal residual disease (MRD) test and found they could predict relapse with a positive predictive value (PPV) of 88% and a negative predictive value (NPV) of 98%.

The test detected relapse a median of 3.5 months quicker than computed tomography (CT) scans.

“Patients with DLBCL with low amounts of disease at relapse have better survival than those with more disease, which is the rationale for surveillance CT scans,” said study author Wyndham Wilson, MD, PhD, of the National Cancer Institute in Bethesda, Maryland.

“Because the ctDNA test detects disease at a molecular level, it detects microscopic disease, which cannot be detected by CT scans, and may improve patient survival. Furthermore, ctDNA is non-invasive and can be employed as frequently needed, unlike surveillance CT scans, which expose patients to radiation and intravenous contrast.”

For this study, Dr Wilson and his colleagues evaluated 126 DLBCL patients who had participated in clinical trials from May 1993 to June 2013 and were followed for a median of 11 years post-treatment.

Surveillance monitoring

To investigate whether ctDNA monitoring could overcome the limitations of standard imaging techniques, the researchers compared serial ctDNA samples to CT scans taken at the same time post-treatment in patients who had achieved complete remission. This was known as “surveillance monitoring.”

The investigators performed surveillance monitoring of ctDNA in 107 patients who achieved complete remission.

The hazard ratio for clinical disease progression was 228 for patients who had detectable ctDNA during surveillance, when compared to patients with undetectable ctDNA (P<0.0001).

Surveillance ctDNA had a PPV of 88.2% and an NPV of 97.8%. And it revealed the risk of recurrence at a median of 3.5 months (range, 0-200 months) before there was evidence of clinical disease.

Interim monitoring

The researchers also analyzed whether the presence of ctDNA at the beginning of the third cycle of treatment predicted relapse, regardless of whether patients achieved complete remission by the end of treatment. This was known as “interim monitoring.”

Of the 108 patients included in the interim monitoring analysis, ctDNA was detected in 24 patients, 15 of whom eventually relapsed. Only 17 of the 84 patients with undetectable interim ctDNA relapsed.

Five years after the interim serum samples were taken, 80.2% of the patients who were negative for ctDNA were relapse-free, as were 41.7% of patients who were positive for ctDNA (P<0.0001).

Detectable interim ctDNA had a PPV of 62.5% and an NPV of 79.8%.

Fourteen of the 15 patients with detectable ctDNA who relapsed did so within 6 months of the end of treatment, as did 7 of the 17 patients without interim ctDNA.

Based on these results, the investigators concluded that surveillance monitoring of ctDNA identifies DLBCL patients at risk of disease recurrence before clinical evidence of disease in most patients, and interim monitoring of ctDNA is a promising biomarker to identify patients at high risk of treatment failure.

This research was funded by Adaptive Biotechnologies, the company developing the clonoSEQ MRD test, as well as the National Cancer Institute.

Wyndham Wilson, MD, PhD

Photo by Larry Young

Surveillance of circulating tumor DNA (ctDNA) can help predict relapse in most patients with diffuse large B-cell lymphoma before there is clinical evidence of the disease, according to a study published in The Lancet Oncology.

Investigators analyzed ctDNA using the clonoSEQ minimal residual disease (MRD) test and found they could predict relapse with a positive predictive value (PPV) of 88% and a negative predictive value (NPV) of 98%.

The test detected relapse a median of 3.5 months quicker than computed tomography (CT) scans.

“Patients with DLBCL with low amounts of disease at relapse have better survival than those with more disease, which is the rationale for surveillance CT scans,” said study author Wyndham Wilson, MD, PhD, of the National Cancer Institute in Bethesda, Maryland.

“Because the ctDNA test detects disease at a molecular level, it detects microscopic disease, which cannot be detected by CT scans, and may improve patient survival. Furthermore, ctDNA is non-invasive and can be employed as frequently needed, unlike surveillance CT scans, which expose patients to radiation and intravenous contrast.”

For this study, Dr Wilson and his colleagues evaluated 126 DLBCL patients who had participated in clinical trials from May 1993 to June 2013 and were followed for a median of 11 years post-treatment.

Surveillance monitoring

To investigate whether ctDNA monitoring could overcome the limitations of standard imaging techniques, the researchers compared serial ctDNA samples to CT scans taken at the same time post-treatment in patients who had achieved complete remission. This was known as “surveillance monitoring.”

The investigators performed surveillance monitoring of ctDNA in 107 patients who achieved complete remission.

The hazard ratio for clinical disease progression was 228 for patients who had detectable ctDNA during surveillance, when compared to patients with undetectable ctDNA (P<0.0001).

Surveillance ctDNA had a PPV of 88.2% and an NPV of 97.8%. And it revealed the risk of recurrence at a median of 3.5 months (range, 0-200 months) before there was evidence of clinical disease.

Interim monitoring

The researchers also analyzed whether the presence of ctDNA at the beginning of the third cycle of treatment predicted relapse, regardless of whether patients achieved complete remission by the end of treatment. This was known as “interim monitoring.”

Of the 108 patients included in the interim monitoring analysis, ctDNA was detected in 24 patients, 15 of whom eventually relapsed. Only 17 of the 84 patients with undetectable interim ctDNA relapsed.

Five years after the interim serum samples were taken, 80.2% of the patients who were negative for ctDNA were relapse-free, as were 41.7% of patients who were positive for ctDNA (P<0.0001).

Detectable interim ctDNA had a PPV of 62.5% and an NPV of 79.8%.

Fourteen of the 15 patients with detectable ctDNA who relapsed did so within 6 months of the end of treatment, as did 7 of the 17 patients without interim ctDNA.

Based on these results, the investigators concluded that surveillance monitoring of ctDNA identifies DLBCL patients at risk of disease recurrence before clinical evidence of disease in most patients, and interim monitoring of ctDNA is a promising biomarker to identify patients at high risk of treatment failure.

This research was funded by Adaptive Biotechnologies, the company developing the clonoSEQ MRD test, as well as the National Cancer Institute.

Micrograph showing DLBCL

The US Food and Drug Administration (FDA) has granted orphan drug designation for IMO-8400, an antagonist of the endosomal toll-like receptors (TLRs) 7, 8, and 9, for the treatment of diffuse large B-cell lymphoma (DLBCL).

The FDA grants orphan designation to drugs intended to treat conditions that affect fewer than 200,000 people in the US.

The designation will provide Idera Pharmaceuticals, the company developing IMO-8400, with certain incentives. These include eligibility for federal grants, research and development tax credits, and a 7-year period of marketing exclusivity if the product is approved.

Relevant research

Preclinical research published in Leukemia showed that the MYD88 L265P oncogenic mutation is an independent prognostic factor in DLBCL. In DLBCL patients with this mutation, TLR signaling is over-activated, which enables tumor cell survival and proliferation.

Data presented at the 2014 AACR Annual Meeting showed that IMO-8400 inhibited the survival and proliferation of DLBCL cells and Waldenstrom’s macroglobulinemia (WM) cells harboring the MYD88 L265P mutation.

A phase 1 trial of IMO-8400 presented at the 2013 FOCIS Annual Meeting showed the drug was active and well-tolerated in 42 healthy subjects. IMO-8400 was given at single and multiple escalating doses up to 0.6 mg/kg for 4 weeks. The drug inhibited immune responses mediated by TLRs 7, 8, and 9.

Idera Pharmaceuticals is currently conducting a phase 1/2 trial of IMO-8400 in patients with relapsed or refractory DLBCL who harbor the MYD88 L265P mutation. The protocol includes 3 dose-escalation cohorts in which IMO-8400 is administered subcutaneously.

Idera is also pursuing clinical development of IMO-8400 in WM. The FDA recently granted the drug orphan designation to treat WM.

Micrograph showing DLBCL

The US Food and Drug Administration (FDA) has granted orphan drug designation for IMO-8400, an antagonist of the endosomal toll-like receptors (TLRs) 7, 8, and 9, for the treatment of diffuse large B-cell lymphoma (DLBCL).

The FDA grants orphan designation to drugs intended to treat conditions that affect fewer than 200,000 people in the US.

The designation will provide Idera Pharmaceuticals, the company developing IMO-8400, with certain incentives. These include eligibility for federal grants, research and development tax credits, and a 7-year period of marketing exclusivity if the product is approved.

Relevant research

Preclinical research published in Leukemia showed that the MYD88 L265P oncogenic mutation is an independent prognostic factor in DLBCL. In DLBCL patients with this mutation, TLR signaling is over-activated, which enables tumor cell survival and proliferation.

Data presented at the 2014 AACR Annual Meeting showed that IMO-8400 inhibited the survival and proliferation of DLBCL cells and Waldenstrom’s macroglobulinemia (WM) cells harboring the MYD88 L265P mutation.

A phase 1 trial of IMO-8400 presented at the 2013 FOCIS Annual Meeting showed the drug was active and well-tolerated in 42 healthy subjects. IMO-8400 was given at single and multiple escalating doses up to 0.6 mg/kg for 4 weeks. The drug inhibited immune responses mediated by TLRs 7, 8, and 9.

Idera Pharmaceuticals is currently conducting a phase 1/2 trial of IMO-8400 in patients with relapsed or refractory DLBCL who harbor the MYD88 L265P mutation. The protocol includes 3 dose-escalation cohorts in which IMO-8400 is administered subcutaneously.

Idera is also pursuing clinical development of IMO-8400 in WM. The FDA recently granted the drug orphan designation to treat WM.

Micrograph showing DLBCL

The US Food and Drug Administration (FDA) has granted orphan drug designation for IMO-8400, an antagonist of the endosomal toll-like receptors (TLRs) 7, 8, and 9, for the treatment of diffuse large B-cell lymphoma (DLBCL).

The FDA grants orphan designation to drugs intended to treat conditions that affect fewer than 200,000 people in the US.

The designation will provide Idera Pharmaceuticals, the company developing IMO-8400, with certain incentives. These include eligibility for federal grants, research and development tax credits, and a 7-year period of marketing exclusivity if the product is approved.

Relevant research

Preclinical research published in Leukemia showed that the MYD88 L265P oncogenic mutation is an independent prognostic factor in DLBCL. In DLBCL patients with this mutation, TLR signaling is over-activated, which enables tumor cell survival and proliferation.

Data presented at the 2014 AACR Annual Meeting showed that IMO-8400 inhibited the survival and proliferation of DLBCL cells and Waldenstrom’s macroglobulinemia (WM) cells harboring the MYD88 L265P mutation.

A phase 1 trial of IMO-8400 presented at the 2013 FOCIS Annual Meeting showed the drug was active and well-tolerated in 42 healthy subjects. IMO-8400 was given at single and multiple escalating doses up to 0.6 mg/kg for 4 weeks. The drug inhibited immune responses mediated by TLRs 7, 8, and 9.

Idera Pharmaceuticals is currently conducting a phase 1/2 trial of IMO-8400 in patients with relapsed or refractory DLBCL who harbor the MYD88 L265P mutation. The protocol includes 3 dose-escalation cohorts in which IMO-8400 is administered subcutaneously.

Idera is also pursuing clinical development of IMO-8400 in WM. The FDA recently granted the drug orphan designation to treat WM.

Doctor examining a child

Photo by Logan Tuttle

New research suggests the prevalence of childhood cancer survivors in the US has increased, and the majority of pediatric patients who have survived 5

or more years beyond cancer diagnosis may have at least one chronic health condition.

About 70% of the childhood cancer survivors studied were estimated to have a mild or moderate chronic condition, and nearly a third were estimated to have a severe, disabling, or life-threatening chronic condition.

“Our study findings highlight that a singular focus on curing cancer yields an incomplete picture of childhood cancer survivorship,” said study author Siobhan M. Phillips, PhD, of Northwestern University Feinberg School of Medicine in Chicago, Illinois.

“The burden of chronic conditions in this population is profound, both in occurrence and severity. Efforts to understand how to effectively decrease morbidity burden and incorporate effective care coordination and rehabilitation models to optimize longevity and well-being in this population should be a priority.”

Dr Phillips and her colleagues reported their findings in Cancer Epidemiology, Biomarkers & Prevention.

The researchers analyzed data on cancer incidence and survival for children who were diagnosed with cancer between 0 and 19 years of age. The data had been recorded between 1975 and 2011 in 9 different US Surveillance, Epidemiology, and End Results (SEER) registries.

The team also used data from the Childhood Cancer Survivor Study (CCSS) cohort, which had information on a range of potential adverse and late effects of cancer treatment from more than 14,000 long-term survivors of childhood cancers who were treated at 26 cancer centers across the US and Canada.

The investigators first obtained estimates of the probability of each measure of morbidity from CCSS and then multiplied these estimates by the relevant number of survivors in the US estimated from the SEER data.

The researchers estimated the number of childhood cancer survivors in the US to be 388,501, which is an increase of 59,849 from the previous estimate made in 2005 by a team from the National Cancer Institute.

Of these patients, about 84% had survived 5 or more years post-diagnosis, and about 45% had survived for 20 years or more.

About 70% of the survivors were estimated to have a mild or moderate chronic condition (grade 1-2), and about 32% were estimated to have a severe, disabling, or life-threatening chronic condition (grade 3-4).

An estimated 35% of the survivors, ages 20 to 49, had neurocognitive dysfunction. About 13% to 17% of survivors in this age group had self-reported functional impairment, activity limitations, impaired mental health, pain, or anxiety/fear.

“We know that many of these morbidities are at least somewhat modifiable in the general population,” Dr Phillips noted. “However, we don’t know if typical population guidelines for preventive behaviors apply to [childhood cancer survivors].”

“We need to develop a better understanding of the multilevel factors—including, but not limited to, physical activity, diet, and treatment characteristics—which influence childhood cancer survivors’ susceptibility to these morbidities in order to effectively prevent and delay their onset.”

Doctor examining a child

Photo by Logan Tuttle

New research suggests the prevalence of childhood cancer survivors in the US has increased, and the majority of pediatric patients who have survived 5

or more years beyond cancer diagnosis may have at least one chronic health condition.

About 70% of the childhood cancer survivors studied were estimated to have a mild or moderate chronic condition, and nearly a third were estimated to have a severe, disabling, or life-threatening chronic condition.

“Our study findings highlight that a singular focus on curing cancer yields an incomplete picture of childhood cancer survivorship,” said study author Siobhan M. Phillips, PhD, of Northwestern University Feinberg School of Medicine in Chicago, Illinois.

“The burden of chronic conditions in this population is profound, both in occurrence and severity. Efforts to understand how to effectively decrease morbidity burden and incorporate effective care coordination and rehabilitation models to optimize longevity and well-being in this population should be a priority.”

Dr Phillips and her colleagues reported their findings in Cancer Epidemiology, Biomarkers & Prevention.

The researchers analyzed data on cancer incidence and survival for children who were diagnosed with cancer between 0 and 19 years of age. The data had been recorded between 1975 and 2011 in 9 different US Surveillance, Epidemiology, and End Results (SEER) registries.

The team also used data from the Childhood Cancer Survivor Study (CCSS) cohort, which had information on a range of potential adverse and late effects of cancer treatment from more than 14,000 long-term survivors of childhood cancers who were treated at 26 cancer centers across the US and Canada.

The investigators first obtained estimates of the probability of each measure of morbidity from CCSS and then multiplied these estimates by the relevant number of survivors in the US estimated from the SEER data.

The researchers estimated the number of childhood cancer survivors in the US to be 388,501, which is an increase of 59,849 from the previous estimate made in 2005 by a team from the National Cancer Institute.

Of these patients, about 84% had survived 5 or more years post-diagnosis, and about 45% had survived for 20 years or more.

About 70% of the survivors were estimated to have a mild or moderate chronic condition (grade 1-2), and about 32% were estimated to have a severe, disabling, or life-threatening chronic condition (grade 3-4).

An estimated 35% of the survivors, ages 20 to 49, had neurocognitive dysfunction. About 13% to 17% of survivors in this age group had self-reported functional impairment, activity limitations, impaired mental health, pain, or anxiety/fear.

“We know that many of these morbidities are at least somewhat modifiable in the general population,” Dr Phillips noted. “However, we don’t know if typical population guidelines for preventive behaviors apply to [childhood cancer survivors].”

“We need to develop a better understanding of the multilevel factors—including, but not limited to, physical activity, diet, and treatment characteristics—which influence childhood cancer survivors’ susceptibility to these morbidities in order to effectively prevent and delay their onset.”

Doctor examining a child

Photo by Logan Tuttle

New research suggests the prevalence of childhood cancer survivors in the US has increased, and the majority of pediatric patients who have survived 5

or more years beyond cancer diagnosis may have at least one chronic health condition.

About 70% of the childhood cancer survivors studied were estimated to have a mild or moderate chronic condition, and nearly a third were estimated to have a severe, disabling, or life-threatening chronic condition.

“Our study findings highlight that a singular focus on curing cancer yields an incomplete picture of childhood cancer survivorship,” said study author Siobhan M. Phillips, PhD, of Northwestern University Feinberg School of Medicine in Chicago, Illinois.

“The burden of chronic conditions in this population is profound, both in occurrence and severity. Efforts to understand how to effectively decrease morbidity burden and incorporate effective care coordination and rehabilitation models to optimize longevity and well-being in this population should be a priority.”

Dr Phillips and her colleagues reported their findings in Cancer Epidemiology, Biomarkers & Prevention.

The researchers analyzed data on cancer incidence and survival for children who were diagnosed with cancer between 0 and 19 years of age. The data had been recorded between 1975 and 2011 in 9 different US Surveillance, Epidemiology, and End Results (SEER) registries.

The team also used data from the Childhood Cancer Survivor Study (CCSS) cohort, which had information on a range of potential adverse and late effects of cancer treatment from more than 14,000 long-term survivors of childhood cancers who were treated at 26 cancer centers across the US and Canada.

The investigators first obtained estimates of the probability of each measure of morbidity from CCSS and then multiplied these estimates by the relevant number of survivors in the US estimated from the SEER data.

The researchers estimated the number of childhood cancer survivors in the US to be 388,501, which is an increase of 59,849 from the previous estimate made in 2005 by a team from the National Cancer Institute.

Of these patients, about 84% had survived 5 or more years post-diagnosis, and about 45% had survived for 20 years or more.

About 70% of the survivors were estimated to have a mild or moderate chronic condition (grade 1-2), and about 32% were estimated to have a severe, disabling, or life-threatening chronic condition (grade 3-4).

An estimated 35% of the survivors, ages 20 to 49, had neurocognitive dysfunction. About 13% to 17% of survivors in this age group had self-reported functional impairment, activity limitations, impaired mental health, pain, or anxiety/fear.

“We know that many of these morbidities are at least somewhat modifiable in the general population,” Dr Phillips noted. “However, we don’t know if typical population guidelines for preventive behaviors apply to [childhood cancer survivors].”

“We need to develop a better understanding of the multilevel factors—including, but not limited to, physical activity, diet, and treatment characteristics—which influence childhood cancer survivors’ susceptibility to these morbidities in order to effectively prevent and delay their onset.”

 

 

Woman sunbathing

 

Vitamin D deficiency may negatively impact outcomes in patients with follicular lymphoma (FL), according to research published in the Journal of Clinical Oncology.

The study showed that FL patients with vitamin D deficiency had inferior progression-free survival (PFS) and overall survival (OS) compared to patients with higher vitamin D levels.

According to researchers, this suggests serum vitamin D might be the first potentially modifiable factor to be associated with survival in FL.

However, additional research is needed to determine the effects of vitamin D supplementation in these patients.

Jonathan W. Friedberg, MD, of the Wilmot Cancer Institute at the University of Rochester in New York, and his colleagues conducted this research, analyzing data from 2 cohorts of FL patients.

One cohort consisted of patients derived from 3 SWOG trials (S9800, S9911, and S0016), and the other consisted of patients from a Lymphoma Study Association (LYSA) trial known as PRIMA.

SWOG patients had received CHOP chemotherapy plus an anti-CD20 antibody (rituximab or iodine-131 tositumomab), and LYSA patients had received rituximab plus chemotherapy (and were randomized to rituximab maintenance or observation).

SWOG cohort

After a median follow-up of 5.4 years, patients with vitamin D deficiency (defined as <20 ng/mL) had significantly inferior PFS (hazard ratio [HR]=2.00; P=0.011) and OS (HR=3.57; P=0.003) compared to patients with higher vitamin D levels.

Results were similar when the researchers adjusted for other variables, such as prognostic index (IPI), body mass index, and latitude (≥ vs <35°N). For PFS, the adjusted HR was 1.97 (P=0.023). And for OS, the adjusted HR was 4.16 (P=0.002).

Multivariable analysis of vitamin D by tertile confirmed that the lowest tertile of vitamin D was associated with a greater increase in the risk of either progression or death, but neither result was significant.

LYSA cohort

After a median follow-up of 6.6 years, patients with vitamin D deficiency (defined as <10 ng/mL) had significantly inferior PFS (HR=1.66; P=0.013) but not OS (HR=1.84; P=0.14) compared to patients with higher vitamin D levels.

Results were similar when the researchers adjusted for other variables, such as prognostic index (FLIPI), body mass index, latitude (Europe vs Australia), and hemoglobin. For PFS, the adjusted HR was 1.50 (P=0.095). For OS, the adjusted HR was 1.92 (P=0.192).

Multivariable analysis of vitamin D by tertile confirmed that the lowest tertile of vitamin D was associated with a greater increase in the risk of either progression or death, but only the association with OS reached statistical significance (HR=5.32; P=0.037).

Dr Friedberg said that, taken together, these results suggest vitamin D levels may be a modifiable factor associated with prognosis in patients with FL.

“Our data, replicated internationally, supports other published observations linking vitamin D deficiency with inferior cancer outcomes,” he said. “However, the mechanisms of this link are likely complex and require further study.”

 

 

Woman sunbathing

 

Vitamin D deficiency may negatively impact outcomes in patients with follicular lymphoma (FL), according to research published in the Journal of Clinical Oncology.

The study showed that FL patients with vitamin D deficiency had inferior progression-free survival (PFS) and overall survival (OS) compared to patients with higher vitamin D levels.

According to researchers, this suggests serum vitamin D might be the first potentially modifiable factor to be associated with survival in FL.

However, additional research is needed to determine the effects of vitamin D supplementation in these patients.

Jonathan W. Friedberg, MD, of the Wilmot Cancer Institute at the University of Rochester in New York, and his colleagues conducted this research, analyzing data from 2 cohorts of FL patients.

One cohort consisted of patients derived from 3 SWOG trials (S9800, S9911, and S0016), and the other consisted of patients from a Lymphoma Study Association (LYSA) trial known as PRIMA.

SWOG patients had received CHOP chemotherapy plus an anti-CD20 antibody (rituximab or iodine-131 tositumomab), and LYSA patients had received rituximab plus chemotherapy (and were randomized to rituximab maintenance or observation).

SWOG cohort

After a median follow-up of 5.4 years, patients with vitamin D deficiency (defined as <20 ng/mL) had significantly inferior PFS (hazard ratio [HR]=2.00; P=0.011) and OS (HR=3.57; P=0.003) compared to patients with higher vitamin D levels.

Results were similar when the researchers adjusted for other variables, such as prognostic index (IPI), body mass index, and latitude (≥ vs <35°N). For PFS, the adjusted HR was 1.97 (P=0.023). And for OS, the adjusted HR was 4.16 (P=0.002).

Multivariable analysis of vitamin D by tertile confirmed that the lowest tertile of vitamin D was associated with a greater increase in the risk of either progression or death, but neither result was significant.

LYSA cohort

After a median follow-up of 6.6 years, patients with vitamin D deficiency (defined as <10 ng/mL) had significantly inferior PFS (HR=1.66; P=0.013) but not OS (HR=1.84; P=0.14) compared to patients with higher vitamin D levels.

Results were similar when the researchers adjusted for other variables, such as prognostic index (FLIPI), body mass index, latitude (Europe vs Australia), and hemoglobin. For PFS, the adjusted HR was 1.50 (P=0.095). For OS, the adjusted HR was 1.92 (P=0.192).

Multivariable analysis of vitamin D by tertile confirmed that the lowest tertile of vitamin D was associated with a greater increase in the risk of either progression or death, but only the association with OS reached statistical significance (HR=5.32; P=0.037).

Dr Friedberg said that, taken together, these results suggest vitamin D levels may be a modifiable factor associated with prognosis in patients with FL.

“Our data, replicated internationally, supports other published observations linking vitamin D deficiency with inferior cancer outcomes,” he said. “However, the mechanisms of this link are likely complex and require further study.”

 

 

Woman sunbathing

 

Vitamin D deficiency may negatively impact outcomes in patients with follicular lymphoma (FL), according to research published in the Journal of Clinical Oncology.

The study showed that FL patients with vitamin D deficiency had inferior progression-free survival (PFS) and overall survival (OS) compared to patients with higher vitamin D levels.

According to researchers, this suggests serum vitamin D might be the first potentially modifiable factor to be associated with survival in FL.

However, additional research is needed to determine the effects of vitamin D supplementation in these patients.

Jonathan W. Friedberg, MD, of the Wilmot Cancer Institute at the University of Rochester in New York, and his colleagues conducted this research, analyzing data from 2 cohorts of FL patients.

One cohort consisted of patients derived from 3 SWOG trials (S9800, S9911, and S0016), and the other consisted of patients from a Lymphoma Study Association (LYSA) trial known as PRIMA.

SWOG patients had received CHOP chemotherapy plus an anti-CD20 antibody (rituximab or iodine-131 tositumomab), and LYSA patients had received rituximab plus chemotherapy (and were randomized to rituximab maintenance or observation).

SWOG cohort

After a median follow-up of 5.4 years, patients with vitamin D deficiency (defined as <20 ng/mL) had significantly inferior PFS (hazard ratio [HR]=2.00; P=0.011) and OS (HR=3.57; P=0.003) compared to patients with higher vitamin D levels.

Results were similar when the researchers adjusted for other variables, such as prognostic index (IPI), body mass index, and latitude (≥ vs <35°N). For PFS, the adjusted HR was 1.97 (P=0.023). And for OS, the adjusted HR was 4.16 (P=0.002).

Multivariable analysis of vitamin D by tertile confirmed that the lowest tertile of vitamin D was associated with a greater increase in the risk of either progression or death, but neither result was significant.

LYSA cohort

After a median follow-up of 6.6 years, patients with vitamin D deficiency (defined as <10 ng/mL) had significantly inferior PFS (HR=1.66; P=0.013) but not OS (HR=1.84; P=0.14) compared to patients with higher vitamin D levels.

Results were similar when the researchers adjusted for other variables, such as prognostic index (FLIPI), body mass index, latitude (Europe vs Australia), and hemoglobin. For PFS, the adjusted HR was 1.50 (P=0.095). For OS, the adjusted HR was 1.92 (P=0.192).

Multivariable analysis of vitamin D by tertile confirmed that the lowest tertile of vitamin D was associated with a greater increase in the risk of either progression or death, but only the association with OS reached statistical significance (HR=5.32; P=0.037).

Dr Friedberg said that, taken together, these results suggest vitamin D levels may be a modifiable factor associated with prognosis in patients with FL.

“Our data, replicated internationally, supports other published observations linking vitamin D deficiency with inferior cancer outcomes,” he said. “However, the mechanisms of this link are likely complex and require further study.”

Blood samples

Photo by Graham Colm

The US Food and Drug Administration (FDA) has granted orphan designation to an immunotherapy known as CMD-003, which is under development to treat Epstein-Barr-virus (EBV)-positive non-Hodgkin lymphomas.

CMD-003 consists of T cells derived from blood samples that are activated and expanded through a proprietary process developed for commercial-scale use.

Researchers have treated more than 250 patients with prototypes of CMD-003. And the prototypes have produced promising results in a range of malignancies.

CMD-003 is under development by Cell Medica and the Center for Cell and Gene Therapy (CAGT) at Baylor College of Medicine, Texas Children’s Hospital, and Houston Methodist Hospital.

Orphan designation from the FDA will provide CMD-003’s developers with several benefits, including accessibility to grants to support clinical development, 7 years of market exclusivity if the treatment is approved in the US, and tax credits on US clinical trials.

CMD-003 prototype

Researchers have not published any trials of CMD-003, but they have studied other EBV-specific T-cell products related to CMD-003.

In their most recent study, published in the Journal of Clinical Oncology, the researchers administered cytotoxic T lymphocytes (CTLs) in 50 patients with EBV-associated Hodgkin or non-Hodgkin lymphoma.

Twenty-nine of the patients were in remission when they received CTL infusions, but they were at a high risk of relapse. The remaining 21 patients had relapsed or refractory disease at the time of CTL infusion.

Twenty-seven of the patients who received CTLs as an adjuvant treatment remained in remission from their disease at 3.1 years after treatment.

Their 2-year event-free survival rate was 82%. None of them died of lymphoma, but 9 died from complications associated with the chemotherapy and radiation they had received.

Of the 21 patients with relapsed or refractory disease, 13 responded to CTL infusions, and 11 patients achieved a complete response. In this group, the 2-year event-free survival rate was about 50%.

The researchers said there were no toxicities that were definitively related to CTL infusion.

One patient had central nervous system deterioration 2 weeks after infusion. This was attributed to disease progression but could possibly have been treatment-related.

Another patient developed respiratory complications about 4 weeks after a second CTL infusion that may have been treatment-related. However, the researchers attributed it to an intercurrent infection, and the patient made a complete recovery.

Blood samples

Photo by Graham Colm

The US Food and Drug Administration (FDA) has granted orphan designation to an immunotherapy known as CMD-003, which is under development to treat Epstein-Barr-virus (EBV)-positive non-Hodgkin lymphomas.

CMD-003 consists of T cells derived from blood samples that are activated and expanded through a proprietary process developed for commercial-scale use.

Researchers have treated more than 250 patients with prototypes of CMD-003. And the prototypes have produced promising results in a range of malignancies.

CMD-003 is under development by Cell Medica and the Center for Cell and Gene Therapy (CAGT) at Baylor College of Medicine, Texas Children’s Hospital, and Houston Methodist Hospital.

Orphan designation from the FDA will provide CMD-003’s developers with several benefits, including accessibility to grants to support clinical development, 7 years of market exclusivity if the treatment is approved in the US, and tax credits on US clinical trials.

CMD-003 prototype

Researchers have not published any trials of CMD-003, but they have studied other EBV-specific T-cell products related to CMD-003.

In their most recent study, published in the Journal of Clinical Oncology, the researchers administered cytotoxic T lymphocytes (CTLs) in 50 patients with EBV-associated Hodgkin or non-Hodgkin lymphoma.

Twenty-nine of the patients were in remission when they received CTL infusions, but they were at a high risk of relapse. The remaining 21 patients had relapsed or refractory disease at the time of CTL infusion.

Twenty-seven of the patients who received CTLs as an adjuvant treatment remained in remission from their disease at 3.1 years after treatment.

Their 2-year event-free survival rate was 82%. None of them died of lymphoma, but 9 died from complications associated with the chemotherapy and radiation they had received.

Of the 21 patients with relapsed or refractory disease, 13 responded to CTL infusions, and 11 patients achieved a complete response. In this group, the 2-year event-free survival rate was about 50%.

The researchers said there were no toxicities that were definitively related to CTL infusion.

One patient had central nervous system deterioration 2 weeks after infusion. This was attributed to disease progression but could possibly have been treatment-related.

Another patient developed respiratory complications about 4 weeks after a second CTL infusion that may have been treatment-related. However, the researchers attributed it to an intercurrent infection, and the patient made a complete recovery.

Blood samples

Photo by Graham Colm

The US Food and Drug Administration (FDA) has granted orphan designation to an immunotherapy known as CMD-003, which is under development to treat Epstein-Barr-virus (EBV)-positive non-Hodgkin lymphomas.

CMD-003 consists of T cells derived from blood samples that are activated and expanded through a proprietary process developed for commercial-scale use.

Researchers have treated more than 250 patients with prototypes of CMD-003. And the prototypes have produced promising results in a range of malignancies.

CMD-003 is under development by Cell Medica and the Center for Cell and Gene Therapy (CAGT) at Baylor College of Medicine, Texas Children’s Hospital, and Houston Methodist Hospital.

Orphan designation from the FDA will provide CMD-003’s developers with several benefits, including accessibility to grants to support clinical development, 7 years of market exclusivity if the treatment is approved in the US, and tax credits on US clinical trials.

CMD-003 prototype

Researchers have not published any trials of CMD-003, but they have studied other EBV-specific T-cell products related to CMD-003.

In their most recent study, published in the Journal of Clinical Oncology, the researchers administered cytotoxic T lymphocytes (CTLs) in 50 patients with EBV-associated Hodgkin or non-Hodgkin lymphoma.

Twenty-nine of the patients were in remission when they received CTL infusions, but they were at a high risk of relapse. The remaining 21 patients had relapsed or refractory disease at the time of CTL infusion.

Twenty-seven of the patients who received CTLs as an adjuvant treatment remained in remission from their disease at 3.1 years after treatment.

Their 2-year event-free survival rate was 82%. None of them died of lymphoma, but 9 died from complications associated with the chemotherapy and radiation they had received.

Of the 21 patients with relapsed or refractory disease, 13 responded to CTL infusions, and 11 patients achieved a complete response. In this group, the 2-year event-free survival rate was about 50%.

The researchers said there were no toxicities that were definitively related to CTL infusion.

One patient had central nervous system deterioration 2 weeks after infusion. This was attributed to disease progression but could possibly have been treatment-related.

Another patient developed respiratory complications about 4 weeks after a second CTL infusion that may have been treatment-related. However, the researchers attributed it to an intercurrent infection, and the patient made a complete recovery.

Researcher in the lab

Photo by Darren Baker

By agreeing upon—and addressing—the aspects of lymphoma research that need the most improvement, the research community could advance the treatment of these diseases, according to a report published in Blood.

The report’s authors said limitations in research infrastructure, funding, and collaborative approaches across research centers present potential challenges on the road to developing better treatments.

And they outlined several “priority areas” that, they believe, require particular attention.

“[Our report] draws focus to our most pressing needs, which, if unaddressed, will prevent transformative changes to how we study and treat these diseases,” said David M. Weinstock, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts.

“Directing our collaborative efforts toward the most high-impact areas will enable us to more rapidly bring life-saving treatments to our patients.”

The report lists the following priority areas:

• Infrastructure

  • Develop an adequate number of disease models for each lymphoma subtype
  • Establish a central repository of biospecimens, cell lines, and in vivo models with open access
  • Organize patient advocacy to support research.

• Research

  • Catalogue how lymphoma cells differ across disease subtypes
  • Better define and identify mutations and other abnormalities associated with the disease
  • Develop strategies to identify high-risk patients who may benefit most from clinical trials
  • Enhance efforts to use immune therapies to cure lymphoma
  • Better understand how lymphoma cells communicate with normal cells.

“[W]e invite clinicians, scientists, advocates, and patients to weigh in on this strategic roadmap so that it reflects the input of everyone in the community,” Dr Weinstock said. “We will share these priorities with funding agencies, advocacy groups, and others who can help us address the challenges we have identified, and thereby accelerate the development of new approaches to understand and eradicate lymphoma.”

To weigh in, visit: http://www.hematology.org/lymphoma-roadmap.

This report was developed after a review of the state of the science in lymphoma that took place at a special ASH Meeting on Lymphoma Biology in August 2014. A second ASH Meeting on Lymphoma Biology is planned for the summer of 2016.

Researcher in the lab

Photo by Darren Baker

By agreeing upon—and addressing—the aspects of lymphoma research that need the most improvement, the research community could advance the treatment of these diseases, according to a report published in Blood.

The report’s authors said limitations in research infrastructure, funding, and collaborative approaches across research centers present potential challenges on the road to developing better treatments.

And they outlined several “priority areas” that, they believe, require particular attention.

“[Our report] draws focus to our most pressing needs, which, if unaddressed, will prevent transformative changes to how we study and treat these diseases,” said David M. Weinstock, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts.

“Directing our collaborative efforts toward the most high-impact areas will enable us to more rapidly bring life-saving treatments to our patients.”

The report lists the following priority areas:

• Infrastructure

  • Develop an adequate number of disease models for each lymphoma subtype
  • Establish a central repository of biospecimens, cell lines, and in vivo models with open access
  • Organize patient advocacy to support research.

• Research

  • Catalogue how lymphoma cells differ across disease subtypes
  • Better define and identify mutations and other abnormalities associated with the disease
  • Develop strategies to identify high-risk patients who may benefit most from clinical trials
  • Enhance efforts to use immune therapies to cure lymphoma
  • Better understand how lymphoma cells communicate with normal cells.

“[W]e invite clinicians, scientists, advocates, and patients to weigh in on this strategic roadmap so that it reflects the input of everyone in the community,” Dr Weinstock said. “We will share these priorities with funding agencies, advocacy groups, and others who can help us address the challenges we have identified, and thereby accelerate the development of new approaches to understand and eradicate lymphoma.”

To weigh in, visit: http://www.hematology.org/lymphoma-roadmap.

This report was developed after a review of the state of the science in lymphoma that took place at a special ASH Meeting on Lymphoma Biology in August 2014. A second ASH Meeting on Lymphoma Biology is planned for the summer of 2016.

Researcher in the lab

Photo by Darren Baker

By agreeing upon—and addressing—the aspects of lymphoma research that need the most improvement, the research community could advance the treatment of these diseases, according to a report published in Blood.

The report’s authors said limitations in research infrastructure, funding, and collaborative approaches across research centers present potential challenges on the road to developing better treatments.

And they outlined several “priority areas” that, they believe, require particular attention.

“[Our report] draws focus to our most pressing needs, which, if unaddressed, will prevent transformative changes to how we study and treat these diseases,” said David M. Weinstock, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts.

“Directing our collaborative efforts toward the most high-impact areas will enable us to more rapidly bring life-saving treatments to our patients.”

The report lists the following priority areas:

• Infrastructure

  • Develop an adequate number of disease models for each lymphoma subtype
  • Establish a central repository of biospecimens, cell lines, and in vivo models with open access
  • Organize patient advocacy to support research.

• Research

  • Catalogue how lymphoma cells differ across disease subtypes
  • Better define and identify mutations and other abnormalities associated with the disease
  • Develop strategies to identify high-risk patients who may benefit most from clinical trials
  • Enhance efforts to use immune therapies to cure lymphoma
  • Better understand how lymphoma cells communicate with normal cells.

“[W]e invite clinicians, scientists, advocates, and patients to weigh in on this strategic roadmap so that it reflects the input of everyone in the community,” Dr Weinstock said. “We will share these priorities with funding agencies, advocacy groups, and others who can help us address the challenges we have identified, and thereby accelerate the development of new approaches to understand and eradicate lymphoma.”

To weigh in, visit: http://www.hematology.org/lymphoma-roadmap.

This report was developed after a review of the state of the science in lymphoma that took place at a special ASH Meeting on Lymphoma Biology in August 2014. A second ASH Meeting on Lymphoma Biology is planned for the summer of 2016.

Red blood cells

Preclinical research suggests an enzyme found in hematopoietic stem cells (HSCs) is key to maintaining periods of inactivity, thereby decreasing the odds that HSCs will divide too often and acquire mutations or cell damage.

Experiments showed that animals lacking this enzyme, inositol trisphosphate 3-kinase B (Itpkb), experience dangerous HSC activation and ultimately succumb to lethal anemia.

“These HSCs remain active too long and then disappear,” said Karsten Sauer, PhD, of The Scripps Research Institute in La Jolla, California.

“As a consequence, the mice lose their red blood cells and die.”

With this new understanding of Itpkb, Dr Sauer and his colleagues believe they are closer to improving therapies for diseases such as bone marrow failure syndrome, anemia, leukemia, and lymphoma.

The team described their research in Blood.

The group set out to investigate the mechanisms that activate and deactivate HSCs. They focused on Itpkb because it is produced in HSCs, and the enzyme is known to dampen activating signaling in other cells.

“We hypothesized that Itpkb might do the same in HSCs to keep them at rest,” Dr Sauer said. “Moreover, Itpkb is an enzyme whose function can be controlled by small molecules. This might facilitate drug development if our hypothesis were true.”

The researchers started with a strain of mice that lacked the gene to produce Itpkb. As expected, these mice developed hyperactive HSCs. Eventually, the mutant HSCs exhausted themselves and stopped producing progenitor cells, so the mice developed severe anemia and died.

Dr Sauer and his colleagues linked the abnormal behavior of the mutant HSCs to a chain of events at the molecular level.

Itpkb’s job is to attach phosphates to molecules called inositols, which then send messages to other parts of the cell. The researchers found that Itpkb can turn one inositol, IP3, into another inositol known as IP4.

This is significant because IP4 controls cell proliferation, cellular metabolism, and aspects of the immune system. The study showed that IP4 also protects HSCs by dampening PI3K/Akt/mTOR signaling.

To confirm this finding, the researchers treated the animals with the mTOR inhibitor rapamycin. The drug halted the abnormal signaling process and prevented the excessive division of HSCs lacking Itpkb. This supported the notion that Itpkb maintains HSCs’ quiescence by dampening PI3K/Akt/mTOR signaling.

Dr Sauer said future research in his lab will focus on studying whether Itpkb has a similar function in human HSCs.

“A major question is whether we can translate our findings into innovative therapies,” he said. “If we can show that Itpkb also keeps human HSCs healthy, this could open avenues to target Itpkb to improve HSC function in bone marrow failure syndromes and immunodeficiencies or to increase the success rates of HSC transplantation therapies for leukemias and lymphomas.”

Red blood cells

Preclinical research suggests an enzyme found in hematopoietic stem cells (HSCs) is key to maintaining periods of inactivity, thereby decreasing the odds that HSCs will divide too often and acquire mutations or cell damage.

Experiments showed that animals lacking this enzyme, inositol trisphosphate 3-kinase B (Itpkb), experience dangerous HSC activation and ultimately succumb to lethal anemia.

“These HSCs remain active too long and then disappear,” said Karsten Sauer, PhD, of The Scripps Research Institute in La Jolla, California.

“As a consequence, the mice lose their red blood cells and die.”

With this new understanding of Itpkb, Dr Sauer and his colleagues believe they are closer to improving therapies for diseases such as bone marrow failure syndrome, anemia, leukemia, and lymphoma.

The team described their research in Blood.

The group set out to investigate the mechanisms that activate and deactivate HSCs. They focused on Itpkb because it is produced in HSCs, and the enzyme is known to dampen activating signaling in other cells.

“We hypothesized that Itpkb might do the same in HSCs to keep them at rest,” Dr Sauer said. “Moreover, Itpkb is an enzyme whose function can be controlled by small molecules. This might facilitate drug development if our hypothesis were true.”

The researchers started with a strain of mice that lacked the gene to produce Itpkb. As expected, these mice developed hyperactive HSCs. Eventually, the mutant HSCs exhausted themselves and stopped producing progenitor cells, so the mice developed severe anemia and died.

Dr Sauer and his colleagues linked the abnormal behavior of the mutant HSCs to a chain of events at the molecular level.

Itpkb’s job is to attach phosphates to molecules called inositols, which then send messages to other parts of the cell. The researchers found that Itpkb can turn one inositol, IP3, into another inositol known as IP4.

This is significant because IP4 controls cell proliferation, cellular metabolism, and aspects of the immune system. The study showed that IP4 also protects HSCs by dampening PI3K/Akt/mTOR signaling.

To confirm this finding, the researchers treated the animals with the mTOR inhibitor rapamycin. The drug halted the abnormal signaling process and prevented the excessive division of HSCs lacking Itpkb. This supported the notion that Itpkb maintains HSCs’ quiescence by dampening PI3K/Akt/mTOR signaling.

Dr Sauer said future research in his lab will focus on studying whether Itpkb has a similar function in human HSCs.

“A major question is whether we can translate our findings into innovative therapies,” he said. “If we can show that Itpkb also keeps human HSCs healthy, this could open avenues to target Itpkb to improve HSC function in bone marrow failure syndromes and immunodeficiencies or to increase the success rates of HSC transplantation therapies for leukemias and lymphomas.”

Red blood cells

Preclinical research suggests an enzyme found in hematopoietic stem cells (HSCs) is key to maintaining periods of inactivity, thereby decreasing the odds that HSCs will divide too often and acquire mutations or cell damage.

Experiments showed that animals lacking this enzyme, inositol trisphosphate 3-kinase B (Itpkb), experience dangerous HSC activation and ultimately succumb to lethal anemia.

“These HSCs remain active too long and then disappear,” said Karsten Sauer, PhD, of The Scripps Research Institute in La Jolla, California.

“As a consequence, the mice lose their red blood cells and die.”

With this new understanding of Itpkb, Dr Sauer and his colleagues believe they are closer to improving therapies for diseases such as bone marrow failure syndrome, anemia, leukemia, and lymphoma.

The team described their research in Blood.

The group set out to investigate the mechanisms that activate and deactivate HSCs. They focused on Itpkb because it is produced in HSCs, and the enzyme is known to dampen activating signaling in other cells.

“We hypothesized that Itpkb might do the same in HSCs to keep them at rest,” Dr Sauer said. “Moreover, Itpkb is an enzyme whose function can be controlled by small molecules. This might facilitate drug development if our hypothesis were true.”

The researchers started with a strain of mice that lacked the gene to produce Itpkb. As expected, these mice developed hyperactive HSCs. Eventually, the mutant HSCs exhausted themselves and stopped producing progenitor cells, so the mice developed severe anemia and died.

Dr Sauer and his colleagues linked the abnormal behavior of the mutant HSCs to a chain of events at the molecular level.

Itpkb’s job is to attach phosphates to molecules called inositols, which then send messages to other parts of the cell. The researchers found that Itpkb can turn one inositol, IP3, into another inositol known as IP4.

This is significant because IP4 controls cell proliferation, cellular metabolism, and aspects of the immune system. The study showed that IP4 also protects HSCs by dampening PI3K/Akt/mTOR signaling.

To confirm this finding, the researchers treated the animals with the mTOR inhibitor rapamycin. The drug halted the abnormal signaling process and prevented the excessive division of HSCs lacking Itpkb. This supported the notion that Itpkb maintains HSCs’ quiescence by dampening PI3K/Akt/mTOR signaling.

Dr Sauer said future research in his lab will focus on studying whether Itpkb has a similar function in human HSCs.

“A major question is whether we can translate our findings into innovative therapies,” he said. “If we can show that Itpkb also keeps human HSCs healthy, this could open avenues to target Itpkb to improve HSC function in bone marrow failure syndromes and immunodeficiencies or to increase the success rates of HSC transplantation therapies for leukemias and lymphomas.”

 

 

Farmer spraying pesticide

Photo by John Messina

 

The International Agency for Research on Cancer (IARC), the specialized cancer agency of the World Health Organization, has found evidence suggesting that 5 organophosphate pesticides may be carcinogenic.

The IARC classified the herbicide glyphosate and the insecticides malathion and diazinon as “probably carcinogenic” to humans and the insecticides tetrachlorvinphos and parathion as “possibly carcinogenic” to humans.

A summary of these findings has been published in The Lancet Oncology.

Glyphosate

For the herbicide glyphosate, the IARC found limited evidence of carcinogenicity in humans. Case-control studies of occupational exposure to glyphosate in the US, Canada, and Sweden showed increased risks for non-Hodgkin lymphoma (NHL).

However, the Agricultural Health Study (AHS) showed no significantly increased risk of NHL in subjects exposed to glyphosate.

A study of community residents showed increases in blood markers of chromosomal damage after glyphosate formulations were sprayed nearby. And glyphosate was shown to cause DNA and chromosomal damage in human cells, although bacterial mutagenesis tests were negative.

In studies of male mice, glyphosate increased the incidence of renal tubule carcinoma and hemangiosarcoma. Glyphosate also increased the incidence of pancreatic islet-cell adenoma in male rats, and a glyphosate formulation promoted skin tumors in mice.

The IARC said glyphosate has the highest global production volume of all herbicides. It is used in agriculture, forestry, urban, and home applications.

Glyphosate has been detected in the air during spraying, in water, and in food. The general population is exposed to the chemical primarily by living near sprayed areas, home use, and diet. But the IARC said the level of exposure observed is generally low.

Malathion

The IARC classified malathion as “probably carcinogenic” for humans based on limited evidence linking the insecticide to NHL and prostate cancer. Occupational use of malathion was associated with an increased risk of prostate cancer in a Canadian case-control study and in the AHS.

Studies of occupational exposures in the US, Canada, and Sweden revealed positive associations between malathion and NHL. However, results of the AHS did not show an association between the insecticide and NHL.

Studies showed that malathion induced DNA and chromosomal damage in humans and animals, although bacterial mutagenesis tests were negative. Results also suggested malathion disrupts hormone pathways.

Experiments in mice showed malathion increased the incidence of hepatocellular adenoma or carcinoma (combined). In rats, the insecticide increased the incidence of thyroid carcinoma in males, hepatocellular adenoma or carcinoma (combined) in females, and mammary gland adenocarcinoma after subcutaneous injection in females.

The IARC said malathion is used in “substantial volumes throughout the world” to control insects in agricultural and residential areas.

Workers may be exposed to malathion during the use and production of the product. The general population may be exposed if they live near sprayed areas, use the product at home, or consume food exposed to the chemical.

Diazinon

The IARC classified diazinon as “probably carcinogenic” for humans based on limited evidence linking the insecticide to NHL, leukemia, and lung cancer.

Two multicenter, case-control studies of agricultural exposures suggested a positive association between diazinon and NHL. The AHS showed positive associations with specific subtypes of NHL but no overall increased risk of NHL. The AHS also suggested an increased risk of leukemia and lung cancer in subjects exposed to diazinon.

Evidence suggested that diazinon induced DNA or chromosomal damage in human and mammalian cells in vitro. In vivo, diazinon increased the incidence of hepatocellular carcinoma in mice and leukemia or lymphoma (combined) in rats, but only in males receiving the low dose in each study.

Diazinon has been used to control insects in agricultural and residential areas. The IARC said production volumes have been relatively low and decreased further after 2006 due to restrictions in the US and the European Union (EU). There was limited information on the use of this pesticide in other countries.

Tetrachlorvinphos

The insecticide tetrachlorvinphos was classified as “possibly carcinogenic” to humans based on convincing evidence that the agent causes cancer in lab animals. The IARC said the evidence in humans was inadequate.

However, tetrachlorvinphos was shown to induce hepatocellular tumors (benign or malignant) in mice, renal tubule tumors (benign or malignant) in male mice, and spleen hemangioma in male rats.

Tetrachlorvinphos is banned in the EU. In the US, the insecticide is still used on livestock and pets (in flea collars). The IARC said there was no information available on tetrachlorvinphos use in other countries.

Parathion

The insecticide parathion was classified as “possibly carcinogenic” to humans based on convincing evidence that the agent causes cancer in lab animals.

Researchers have observed associations between the insecticide and cancers in several tissues in occupational studies. But the IARC said the evidence that parathion is carcinogenic in humans remains sparse.

Experiments in mice showed that parathion increased the incidence of bronchioloalveolar adenoma and/or carcinoma in males and lymphoma in females. In rats, parathion induced adrenal cortical adenoma or carcinoma (combined), malignant pancreatic tumors, and thyroid follicular cell adenoma in males, and mammary gland adenocarcinoma (after subcutaneous injection in females).

Parathion use has been severely restricted since the 1980s, and all authorized uses of this chemical were cancelled in the EU and the US by 2003.

 

 

Farmer spraying pesticide

Photo by John Messina

 

The International Agency for Research on Cancer (IARC), the specialized cancer agency of the World Health Organization, has found evidence suggesting that 5 organophosphate pesticides may be carcinogenic.

The IARC classified the herbicide glyphosate and the insecticides malathion and diazinon as “probably carcinogenic” to humans and the insecticides tetrachlorvinphos and parathion as “possibly carcinogenic” to humans.

A summary of these findings has been published in The Lancet Oncology.

Glyphosate

For the herbicide glyphosate, the IARC found limited evidence of carcinogenicity in humans. Case-control studies of occupational exposure to glyphosate in the US, Canada, and Sweden showed increased risks for non-Hodgkin lymphoma (NHL).

However, the Agricultural Health Study (AHS) showed no significantly increased risk of NHL in subjects exposed to glyphosate.

A study of community residents showed increases in blood markers of chromosomal damage after glyphosate formulations were sprayed nearby. And glyphosate was shown to cause DNA and chromosomal damage in human cells, although bacterial mutagenesis tests were negative.

In studies of male mice, glyphosate increased the incidence of renal tubule carcinoma and hemangiosarcoma. Glyphosate also increased the incidence of pancreatic islet-cell adenoma in male rats, and a glyphosate formulation promoted skin tumors in mice.

The IARC said glyphosate has the highest global production volume of all herbicides. It is used in agriculture, forestry, urban, and home applications.

Glyphosate has been detected in the air during spraying, in water, and in food. The general population is exposed to the chemical primarily by living near sprayed areas, home use, and diet. But the IARC said the level of exposure observed is generally low.

Malathion

The IARC classified malathion as “probably carcinogenic” for humans based on limited evidence linking the insecticide to NHL and prostate cancer. Occupational use of malathion was associated with an increased risk of prostate cancer in a Canadian case-control study and in the AHS.

Studies of occupational exposures in the US, Canada, and Sweden revealed positive associations between malathion and NHL. However, results of the AHS did not show an association between the insecticide and NHL.

Studies showed that malathion induced DNA and chromosomal damage in humans and animals, although bacterial mutagenesis tests were negative. Results also suggested malathion disrupts hormone pathways.

Experiments in mice showed malathion increased the incidence of hepatocellular adenoma or carcinoma (combined). In rats, the insecticide increased the incidence of thyroid carcinoma in males, hepatocellular adenoma or carcinoma (combined) in females, and mammary gland adenocarcinoma after subcutaneous injection in females.

The IARC said malathion is used in “substantial volumes throughout the world” to control insects in agricultural and residential areas.

Workers may be exposed to malathion during the use and production of the product. The general population may be exposed if they live near sprayed areas, use the product at home, or consume food exposed to the chemical.

Diazinon

The IARC classified diazinon as “probably carcinogenic” for humans based on limited evidence linking the insecticide to NHL, leukemia, and lung cancer.

Two multicenter, case-control studies of agricultural exposures suggested a positive association between diazinon and NHL. The AHS showed positive associations with specific subtypes of NHL but no overall increased risk of NHL. The AHS also suggested an increased risk of leukemia and lung cancer in subjects exposed to diazinon.

Evidence suggested that diazinon induced DNA or chromosomal damage in human and mammalian cells in vitro. In vivo, diazinon increased the incidence of hepatocellular carcinoma in mice and leukemia or lymphoma (combined) in rats, but only in males receiving the low dose in each study.

Diazinon has been used to control insects in agricultural and residential areas. The IARC said production volumes have been relatively low and decreased further after 2006 due to restrictions in the US and the European Union (EU). There was limited information on the use of this pesticide in other countries.

Tetrachlorvinphos

The insecticide tetrachlorvinphos was classified as “possibly carcinogenic” to humans based on convincing evidence that the agent causes cancer in lab animals. The IARC said the evidence in humans was inadequate.

However, tetrachlorvinphos was shown to induce hepatocellular tumors (benign or malignant) in mice, renal tubule tumors (benign or malignant) in male mice, and spleen hemangioma in male rats.

Tetrachlorvinphos is banned in the EU. In the US, the insecticide is still used on livestock and pets (in flea collars). The IARC said there was no information available on tetrachlorvinphos use in other countries.

Parathion

The insecticide parathion was classified as “possibly carcinogenic” to humans based on convincing evidence that the agent causes cancer in lab animals.

Researchers have observed associations between the insecticide and cancers in several tissues in occupational studies. But the IARC said the evidence that parathion is carcinogenic in humans remains sparse.

Experiments in mice showed that parathion increased the incidence of bronchioloalveolar adenoma and/or carcinoma in males and lymphoma in females. In rats, parathion induced adrenal cortical adenoma or carcinoma (combined), malignant pancreatic tumors, and thyroid follicular cell adenoma in males, and mammary gland adenocarcinoma (after subcutaneous injection in females).

Parathion use has been severely restricted since the 1980s, and all authorized uses of this chemical were cancelled in the EU and the US by 2003.

 

 

Farmer spraying pesticide

Photo by John Messina

 

The International Agency for Research on Cancer (IARC), the specialized cancer agency of the World Health Organization, has found evidence suggesting that 5 organophosphate pesticides may be carcinogenic.

The IARC classified the herbicide glyphosate and the insecticides malathion and diazinon as “probably carcinogenic” to humans and the insecticides tetrachlorvinphos and parathion as “possibly carcinogenic” to humans.

A summary of these findings has been published in The Lancet Oncology.

Glyphosate

For the herbicide glyphosate, the IARC found limited evidence of carcinogenicity in humans. Case-control studies of occupational exposure to glyphosate in the US, Canada, and Sweden showed increased risks for non-Hodgkin lymphoma (NHL).

However, the Agricultural Health Study (AHS) showed no significantly increased risk of NHL in subjects exposed to glyphosate.

A study of community residents showed increases in blood markers of chromosomal damage after glyphosate formulations were sprayed nearby. And glyphosate was shown to cause DNA and chromosomal damage in human cells, although bacterial mutagenesis tests were negative.

In studies of male mice, glyphosate increased the incidence of renal tubule carcinoma and hemangiosarcoma. Glyphosate also increased the incidence of pancreatic islet-cell adenoma in male rats, and a glyphosate formulation promoted skin tumors in mice.

The IARC said glyphosate has the highest global production volume of all herbicides. It is used in agriculture, forestry, urban, and home applications.

Glyphosate has been detected in the air during spraying, in water, and in food. The general population is exposed to the chemical primarily by living near sprayed areas, home use, and diet. But the IARC said the level of exposure observed is generally low.

Malathion

The IARC classified malathion as “probably carcinogenic” for humans based on limited evidence linking the insecticide to NHL and prostate cancer. Occupational use of malathion was associated with an increased risk of prostate cancer in a Canadian case-control study and in the AHS.

Studies of occupational exposures in the US, Canada, and Sweden revealed positive associations between malathion and NHL. However, results of the AHS did not show an association between the insecticide and NHL.

Studies showed that malathion induced DNA and chromosomal damage in humans and animals, although bacterial mutagenesis tests were negative. Results also suggested malathion disrupts hormone pathways.

Experiments in mice showed malathion increased the incidence of hepatocellular adenoma or carcinoma (combined). In rats, the insecticide increased the incidence of thyroid carcinoma in males, hepatocellular adenoma or carcinoma (combined) in females, and mammary gland adenocarcinoma after subcutaneous injection in females.

The IARC said malathion is used in “substantial volumes throughout the world” to control insects in agricultural and residential areas.

Workers may be exposed to malathion during the use and production of the product. The general population may be exposed if they live near sprayed areas, use the product at home, or consume food exposed to the chemical.

Diazinon

The IARC classified diazinon as “probably carcinogenic” for humans based on limited evidence linking the insecticide to NHL, leukemia, and lung cancer.

Two multicenter, case-control studies of agricultural exposures suggested a positive association between diazinon and NHL. The AHS showed positive associations with specific subtypes of NHL but no overall increased risk of NHL. The AHS also suggested an increased risk of leukemia and lung cancer in subjects exposed to diazinon.

Evidence suggested that diazinon induced DNA or chromosomal damage in human and mammalian cells in vitro. In vivo, diazinon increased the incidence of hepatocellular carcinoma in mice and leukemia or lymphoma (combined) in rats, but only in males receiving the low dose in each study.

Diazinon has been used to control insects in agricultural and residential areas. The IARC said production volumes have been relatively low and decreased further after 2006 due to restrictions in the US and the European Union (EU). There was limited information on the use of this pesticide in other countries.

Tetrachlorvinphos

The insecticide tetrachlorvinphos was classified as “possibly carcinogenic” to humans based on convincing evidence that the agent causes cancer in lab animals. The IARC said the evidence in humans was inadequate.

However, tetrachlorvinphos was shown to induce hepatocellular tumors (benign or malignant) in mice, renal tubule tumors (benign or malignant) in male mice, and spleen hemangioma in male rats.

Tetrachlorvinphos is banned in the EU. In the US, the insecticide is still used on livestock and pets (in flea collars). The IARC said there was no information available on tetrachlorvinphos use in other countries.

Parathion

The insecticide parathion was classified as “possibly carcinogenic” to humans based on convincing evidence that the agent causes cancer in lab animals.

Researchers have observed associations between the insecticide and cancers in several tissues in occupational studies. But the IARC said the evidence that parathion is carcinogenic in humans remains sparse.

Experiments in mice showed that parathion increased the incidence of bronchioloalveolar adenoma and/or carcinoma in males and lymphoma in females. In rats, parathion induced adrenal cortical adenoma or carcinoma (combined), malignant pancreatic tumors, and thyroid follicular cell adenoma in males, and mammary gland adenocarcinoma (after subcutaneous injection in females).

Parathion use has been severely restricted since the 1980s, and all authorized uses of this chemical were cancelled in the EU and the US by 2003.