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Patients with myeloproliferative neoplasms treated with Janus-kinase (JAK) 1/2 inhibitors may be at significantly increased risk of aggressive B cell non-Hodgkin lymphomas, according to a study published in Blood.

A retrospective cohort study of 626 Viennese patients with myeloproliferative neoplasms – 69 of whom were treated with JAK1/2 inhibitors – found that 4 of the 69 patients (5.8%) developed aggressive B-cell lymphoma, compared with just 2 patients (0.36%) in the rest of the group. This represented a significant, 16-fold higher risk of aggressive B cell lymphoma associated with JAK1/2 inhibitor therapy (P = .0017).

The lymphoma was diagnosed within 13-35 months of starting JAK1/2 inhibitors. In three patients, the disease was in the bone marrow and peripheral blood, one patient had it in mammary tissue, and another had it in mucosal tissue. All four lymphomas showed positive MYC and p53 staining.

All four patients had been treated with ruxolitinib, one was also treated with fedratinib, and three of the four had been pretreated with alkylating agents.

Meanwhile, a second retrospective cohort study in Paris of 929 patients with myeloproliferative neoplasms, reported in the same paper, found that 3.51% of those treated with ruxolitinib developed lymphoma, compared with 0.23% of conventionally-treated patients.

Using archived bone marrow samples from 54 of the 69 patients treated with JAK1/2 inhibitors, researchers discovered that 15.9% of them – including three of the B-cell lymphoma patients (the fourth was not tested) – had a preexisting B cell clone. This was present as early as 47-70 months before the lymphoma diagnosis.

“In patients, the clonal B-cell population was present as long as 6 years before overt lymphoma and preceded JAK1/2 inhibition which offers the opportunity to determine patients at risk,” wrote Edit Porpaczy, MD, of the Comprehensive Cancer Center at the Medical University of Vienna, and her coauthors. “Targeted inhibition of JAK-STAT signaling appears to be required to trigger the appearance of the B-cell clone as other treatments eliminating the myeloid cell load in men do not exert a comparable effect.”

In the Viennese cohort, three of the lymphomas were aggressive CD19⁺ B-cell type, and the fourth was a nonspecified high-grade B-cell lymphoma.

Researchers also looked at the effects of JAK1/2 inhibition in STAT1^-/- mice, and found that two-thirds developed a spontaneous myeloid hyperplasia with the concomitant presence of aberrant B-cells.

“Upon STAT1-deficiency myeloid hyperplasia is paralleled by the occurrence of a malignant B-cell clone, which evolves into disease upon bone-marrow transplantation and gives rise to a leukemic lymphoma phenotype,” the authors wrote.

The study was supported by the Austrian Science Fund, the Anniversary Fund of the Austrian National Bank and the WWTF Precision Medicine Program. Several authors reported support, funding or advisory board positions with the pharmaceutical industry.

SOURCE: Porpaczy E et al. Blood. 2018 Jun 14. doi: 10.1182/blood-2017-10-810739.

Patients with myeloproliferative neoplasms treated with Janus-kinase (JAK) 1/2 inhibitors may be at significantly increased risk of aggressive B cell non-Hodgkin lymphomas, according to a study published in Blood.

A retrospective cohort study of 626 Viennese patients with myeloproliferative neoplasms – 69 of whom were treated with JAK1/2 inhibitors – found that 4 of the 69 patients (5.8%) developed aggressive B-cell lymphoma, compared with just 2 patients (0.36%) in the rest of the group. This represented a significant, 16-fold higher risk of aggressive B cell lymphoma associated with JAK1/2 inhibitor therapy (P = .0017).

The lymphoma was diagnosed within 13-35 months of starting JAK1/2 inhibitors. In three patients, the disease was in the bone marrow and peripheral blood, one patient had it in mammary tissue, and another had it in mucosal tissue. All four lymphomas showed positive MYC and p53 staining.

All four patients had been treated with ruxolitinib, one was also treated with fedratinib, and three of the four had been pretreated with alkylating agents.

Meanwhile, a second retrospective cohort study in Paris of 929 patients with myeloproliferative neoplasms, reported in the same paper, found that 3.51% of those treated with ruxolitinib developed lymphoma, compared with 0.23% of conventionally-treated patients.

Using archived bone marrow samples from 54 of the 69 patients treated with JAK1/2 inhibitors, researchers discovered that 15.9% of them – including three of the B-cell lymphoma patients (the fourth was not tested) – had a preexisting B cell clone. This was present as early as 47-70 months before the lymphoma diagnosis.

“In patients, the clonal B-cell population was present as long as 6 years before overt lymphoma and preceded JAK1/2 inhibition which offers the opportunity to determine patients at risk,” wrote Edit Porpaczy, MD, of the Comprehensive Cancer Center at the Medical University of Vienna, and her coauthors. “Targeted inhibition of JAK-STAT signaling appears to be required to trigger the appearance of the B-cell clone as other treatments eliminating the myeloid cell load in men do not exert a comparable effect.”

In the Viennese cohort, three of the lymphomas were aggressive CD19⁺ B-cell type, and the fourth was a nonspecified high-grade B-cell lymphoma.

Researchers also looked at the effects of JAK1/2 inhibition in STAT1^-/- mice, and found that two-thirds developed a spontaneous myeloid hyperplasia with the concomitant presence of aberrant B-cells.

“Upon STAT1-deficiency myeloid hyperplasia is paralleled by the occurrence of a malignant B-cell clone, which evolves into disease upon bone-marrow transplantation and gives rise to a leukemic lymphoma phenotype,” the authors wrote.

The study was supported by the Austrian Science Fund, the Anniversary Fund of the Austrian National Bank and the WWTF Precision Medicine Program. Several authors reported support, funding or advisory board positions with the pharmaceutical industry.

SOURCE: Porpaczy E et al. Blood. 2018 Jun 14. doi: 10.1182/blood-2017-10-810739.

Patients with myeloproliferative neoplasms treated with Janus-kinase (JAK) 1/2 inhibitors may be at significantly increased risk of aggressive B cell non-Hodgkin lymphomas, according to a study published in Blood.

A retrospective cohort study of 626 Viennese patients with myeloproliferative neoplasms – 69 of whom were treated with JAK1/2 inhibitors – found that 4 of the 69 patients (5.8%) developed aggressive B-cell lymphoma, compared with just 2 patients (0.36%) in the rest of the group. This represented a significant, 16-fold higher risk of aggressive B cell lymphoma associated with JAK1/2 inhibitor therapy (P = .0017).

The lymphoma was diagnosed within 13-35 months of starting JAK1/2 inhibitors. In three patients, the disease was in the bone marrow and peripheral blood, one patient had it in mammary tissue, and another had it in mucosal tissue. All four lymphomas showed positive MYC and p53 staining.

All four patients had been treated with ruxolitinib, one was also treated with fedratinib, and three of the four had been pretreated with alkylating agents.

Meanwhile, a second retrospective cohort study in Paris of 929 patients with myeloproliferative neoplasms, reported in the same paper, found that 3.51% of those treated with ruxolitinib developed lymphoma, compared with 0.23% of conventionally-treated patients.

Using archived bone marrow samples from 54 of the 69 patients treated with JAK1/2 inhibitors, researchers discovered that 15.9% of them – including three of the B-cell lymphoma patients (the fourth was not tested) – had a preexisting B cell clone. This was present as early as 47-70 months before the lymphoma diagnosis.

“In patients, the clonal B-cell population was present as long as 6 years before overt lymphoma and preceded JAK1/2 inhibition which offers the opportunity to determine patients at risk,” wrote Edit Porpaczy, MD, of the Comprehensive Cancer Center at the Medical University of Vienna, and her coauthors. “Targeted inhibition of JAK-STAT signaling appears to be required to trigger the appearance of the B-cell clone as other treatments eliminating the myeloid cell load in men do not exert a comparable effect.”

In the Viennese cohort, three of the lymphomas were aggressive CD19⁺ B-cell type, and the fourth was a nonspecified high-grade B-cell lymphoma.

Researchers also looked at the effects of JAK1/2 inhibition in STAT1^-/- mice, and found that two-thirds developed a spontaneous myeloid hyperplasia with the concomitant presence of aberrant B-cells.

“Upon STAT1-deficiency myeloid hyperplasia is paralleled by the occurrence of a malignant B-cell clone, which evolves into disease upon bone-marrow transplantation and gives rise to a leukemic lymphoma phenotype,” the authors wrote.

The study was supported by the Austrian Science Fund, the Anniversary Fund of the Austrian National Bank and the WWTF Precision Medicine Program. Several authors reported support, funding or advisory board positions with the pharmaceutical industry.

SOURCE: Porpaczy E et al. Blood. 2018 Jun 14. doi: 10.1182/blood-2017-10-810739.

The Food and Drug Administration has expanded the indication for Orkambi (lumacaftor/ivacaftor) to include patients who are aged as young as 2 years with cystic fibrosis (CF), according to its manufacturer, Vertex Pharmaceuticals. Specifically, the drug is meant to treat the most common underlying cause of CF – having two copies of the F508del-CFTR mutation – and is the first drug to treat it.

The approval is based on a phase 3, two-part, open-label, multicenter study that assessed various doses in patents aged 2-5 years. The study demonstrated safety and tolerability in that age group equivalent to that seen in older patients. The drug is expected to be available for this age group within 2-4 weeks of this approval.

Available as oral granules in two doses for weight-based dosing (either lumacaftor 100 mg/ivacaftor 125 mg or lumacaftor 150 mg/ivacaftor 188 mg), the compound targets the defective chloride channels responsible for CF; the two halves work together to increase the number of chloride channels on cell surfaces and also improve their function.

Orkambi should be prescribed only for patients with CF who have the dual F508del-CFTR mutation; it is not indicated for other types of CF. Patients should not take this drug if they are taking drugs such as rifampin, phenytoin, triazolam, or cyclosporine because of possible drug interactions. It can also lead to worsening liver function and elevated blood liver enzymes, increased blood pressure, or cataracts. The most common side effects include breathing problems, nausea, fatigue, and rash. Full prescribing information is available on the FDA website.
 

cpalmer@mdedge.com

The Food and Drug Administration has expanded the indication for Orkambi (lumacaftor/ivacaftor) to include patients who are aged as young as 2 years with cystic fibrosis (CF), according to its manufacturer, Vertex Pharmaceuticals. Specifically, the drug is meant to treat the most common underlying cause of CF – having two copies of the F508del-CFTR mutation – and is the first drug to treat it.

The approval is based on a phase 3, two-part, open-label, multicenter study that assessed various doses in patents aged 2-5 years. The study demonstrated safety and tolerability in that age group equivalent to that seen in older patients. The drug is expected to be available for this age group within 2-4 weeks of this approval.

Available as oral granules in two doses for weight-based dosing (either lumacaftor 100 mg/ivacaftor 125 mg or lumacaftor 150 mg/ivacaftor 188 mg), the compound targets the defective chloride channels responsible for CF; the two halves work together to increase the number of chloride channels on cell surfaces and also improve their function.

Orkambi should be prescribed only for patients with CF who have the dual F508del-CFTR mutation; it is not indicated for other types of CF. Patients should not take this drug if they are taking drugs such as rifampin, phenytoin, triazolam, or cyclosporine because of possible drug interactions. It can also lead to worsening liver function and elevated blood liver enzymes, increased blood pressure, or cataracts. The most common side effects include breathing problems, nausea, fatigue, and rash. Full prescribing information is available on the FDA website.
 

cpalmer@mdedge.com

The Food and Drug Administration has expanded the indication for Orkambi (lumacaftor/ivacaftor) to include patients who are aged as young as 2 years with cystic fibrosis (CF), according to its manufacturer, Vertex Pharmaceuticals. Specifically, the drug is meant to treat the most common underlying cause of CF – having two copies of the F508del-CFTR mutation – and is the first drug to treat it.

The approval is based on a phase 3, two-part, open-label, multicenter study that assessed various doses in patents aged 2-5 years. The study demonstrated safety and tolerability in that age group equivalent to that seen in older patients. The drug is expected to be available for this age group within 2-4 weeks of this approval.

Available as oral granules in two doses for weight-based dosing (either lumacaftor 100 mg/ivacaftor 125 mg or lumacaftor 150 mg/ivacaftor 188 mg), the compound targets the defective chloride channels responsible for CF; the two halves work together to increase the number of chloride channels on cell surfaces and also improve their function.

Orkambi should be prescribed only for patients with CF who have the dual F508del-CFTR mutation; it is not indicated for other types of CF. Patients should not take this drug if they are taking drugs such as rifampin, phenytoin, triazolam, or cyclosporine because of possible drug interactions. It can also lead to worsening liver function and elevated blood liver enzymes, increased blood pressure, or cataracts. The most common side effects include breathing problems, nausea, fatigue, and rash. Full prescribing information is available on the FDA website.
 

cpalmer@mdedge.com

Fludarabine, cyclophosphamide, and rituximab are recommended as initial therapy for patients with chronic lymphocytic leukemia who do not have TP53 disruption, according to new guidelines from the British Society for Haematology.

The guidelines update the 2012 recommendations on chronic lymphocytic leukemia (CLL) to include “significant” developments in treatment. They were published in the British Journal of Haematology.

Anna H. Schuh, MD, of the department of oncology at the University of Oxford (England), and her coauthors noted that, while these guidelines apply to treatments available outside clinical trials, wherever possible patients with CLL should be treated within the clinical trial setting.

While recommending fludarabine, cyclophosphamide, and rituximab as first-line therapy, the guideline authors acknowledged that the combination of bendamustine and rituximab is an acceptable alternative for patients who could not take the triple therapy because of comorbidities such as advanced age, renal impairment, or issues with marrow capacity.

Similarly, less-fit patients could also be considered for chlorambucil-obinutuzumab or chlorambucil-ofatumumab combinations.

All patients diagnosed with CLL should be tested for TP53 deletions and mutations before each line of therapy, the guideline committee recommended. TP53 disruption makes chemoimmunotherapy ineffective because of either a deletion of chromosome 17p or a mutation in the TP53 gene. However, there is compelling evidence for the efficacy of ibrutinib in these patients, or idelalisib and rituximab for those with cardiac disease or receiving vitamin K antagonists.

With respect to maintenance therapy, the guidelines noted that this was not routinely recommended in CLL as “it is unclear to what extent the progression-free survival benefit is offset by long-term toxicity.”

Patients who are refractory to chemoimmunotherapy, who have relapsed, or who cannot be retreated with chemoimmunotherapy should be treated with idelalisib with rituximab or ibrutinib monotherapy, the guidelines suggested.

“Deciding whether ibrutinib or idelalisib with rituximab is most appropriate for an individual patient depends on a range of factors, including toxicity profile and convenience of delivery,” the authors wrote. However, they noted that the value of adding bendamustine to either option was unclear as research had not shown significant, associated gains in median progression-free survival.

Allogeneic stem cell transplantation should be considered as a treatment option for patients who have either failed chemotherapy, have a TP53 disruption and have not responded to B-cell receptor signaling pathway inhibitors such as ibrutinib, or have a Richter transformation.

The guidelines also addressed the issue of autoimmune cytopenias, which occur in 5%-10% of patients with CLL and can actually precede the diagnosis of CLL in about 9% of cases.

In patients where autoimmune cytopenia is the dominant clinical feature, they should be treated with corticosteroids, intravenous immunoglobulin, or rituximab. However, for patients where the cytopenia is triggered by CLL therapy, the guidelines recommended halting treatment and beginning immunosuppression.

The guideline development was supported by the British Society for Haematology. The UK CLL Forum is a registered charity that receives funding from a number of pharmaceutical companies.

SOURCE: Schuh AH et al. Br J Haematol. 2018 Jul 15. doi: 10.1111/bjh.15460.

Fludarabine, cyclophosphamide, and rituximab are recommended as initial therapy for patients with chronic lymphocytic leukemia who do not have TP53 disruption, according to new guidelines from the British Society for Haematology.

The guidelines update the 2012 recommendations on chronic lymphocytic leukemia (CLL) to include “significant” developments in treatment. They were published in the British Journal of Haematology.

Anna H. Schuh, MD, of the department of oncology at the University of Oxford (England), and her coauthors noted that, while these guidelines apply to treatments available outside clinical trials, wherever possible patients with CLL should be treated within the clinical trial setting.

While recommending fludarabine, cyclophosphamide, and rituximab as first-line therapy, the guideline authors acknowledged that the combination of bendamustine and rituximab is an acceptable alternative for patients who could not take the triple therapy because of comorbidities such as advanced age, renal impairment, or issues with marrow capacity.

Similarly, less-fit patients could also be considered for chlorambucil-obinutuzumab or chlorambucil-ofatumumab combinations.

All patients diagnosed with CLL should be tested for TP53 deletions and mutations before each line of therapy, the guideline committee recommended. TP53 disruption makes chemoimmunotherapy ineffective because of either a deletion of chromosome 17p or a mutation in the TP53 gene. However, there is compelling evidence for the efficacy of ibrutinib in these patients, or idelalisib and rituximab for those with cardiac disease or receiving vitamin K antagonists.

With respect to maintenance therapy, the guidelines noted that this was not routinely recommended in CLL as “it is unclear to what extent the progression-free survival benefit is offset by long-term toxicity.”

Patients who are refractory to chemoimmunotherapy, who have relapsed, or who cannot be retreated with chemoimmunotherapy should be treated with idelalisib with rituximab or ibrutinib monotherapy, the guidelines suggested.

“Deciding whether ibrutinib or idelalisib with rituximab is most appropriate for an individual patient depends on a range of factors, including toxicity profile and convenience of delivery,” the authors wrote. However, they noted that the value of adding bendamustine to either option was unclear as research had not shown significant, associated gains in median progression-free survival.

Allogeneic stem cell transplantation should be considered as a treatment option for patients who have either failed chemotherapy, have a TP53 disruption and have not responded to B-cell receptor signaling pathway inhibitors such as ibrutinib, or have a Richter transformation.

The guidelines also addressed the issue of autoimmune cytopenias, which occur in 5%-10% of patients with CLL and can actually precede the diagnosis of CLL in about 9% of cases.

In patients where autoimmune cytopenia is the dominant clinical feature, they should be treated with corticosteroids, intravenous immunoglobulin, or rituximab. However, for patients where the cytopenia is triggered by CLL therapy, the guidelines recommended halting treatment and beginning immunosuppression.

The guideline development was supported by the British Society for Haematology. The UK CLL Forum is a registered charity that receives funding from a number of pharmaceutical companies.

SOURCE: Schuh AH et al. Br J Haematol. 2018 Jul 15. doi: 10.1111/bjh.15460.

Fludarabine, cyclophosphamide, and rituximab are recommended as initial therapy for patients with chronic lymphocytic leukemia who do not have TP53 disruption, according to new guidelines from the British Society for Haematology.

The guidelines update the 2012 recommendations on chronic lymphocytic leukemia (CLL) to include “significant” developments in treatment. They were published in the British Journal of Haematology.

Anna H. Schuh, MD, of the department of oncology at the University of Oxford (England), and her coauthors noted that, while these guidelines apply to treatments available outside clinical trials, wherever possible patients with CLL should be treated within the clinical trial setting.

While recommending fludarabine, cyclophosphamide, and rituximab as first-line therapy, the guideline authors acknowledged that the combination of bendamustine and rituximab is an acceptable alternative for patients who could not take the triple therapy because of comorbidities such as advanced age, renal impairment, or issues with marrow capacity.

Similarly, less-fit patients could also be considered for chlorambucil-obinutuzumab or chlorambucil-ofatumumab combinations.

All patients diagnosed with CLL should be tested for TP53 deletions and mutations before each line of therapy, the guideline committee recommended. TP53 disruption makes chemoimmunotherapy ineffective because of either a deletion of chromosome 17p or a mutation in the TP53 gene. However, there is compelling evidence for the efficacy of ibrutinib in these patients, or idelalisib and rituximab for those with cardiac disease or receiving vitamin K antagonists.

With respect to maintenance therapy, the guidelines noted that this was not routinely recommended in CLL as “it is unclear to what extent the progression-free survival benefit is offset by long-term toxicity.”

Patients who are refractory to chemoimmunotherapy, who have relapsed, or who cannot be retreated with chemoimmunotherapy should be treated with idelalisib with rituximab or ibrutinib monotherapy, the guidelines suggested.

“Deciding whether ibrutinib or idelalisib with rituximab is most appropriate for an individual patient depends on a range of factors, including toxicity profile and convenience of delivery,” the authors wrote. However, they noted that the value of adding bendamustine to either option was unclear as research had not shown significant, associated gains in median progression-free survival.

Allogeneic stem cell transplantation should be considered as a treatment option for patients who have either failed chemotherapy, have a TP53 disruption and have not responded to B-cell receptor signaling pathway inhibitors such as ibrutinib, or have a Richter transformation.

The guidelines also addressed the issue of autoimmune cytopenias, which occur in 5%-10% of patients with CLL and can actually precede the diagnosis of CLL in about 9% of cases.

In patients where autoimmune cytopenia is the dominant clinical feature, they should be treated with corticosteroids, intravenous immunoglobulin, or rituximab. However, for patients where the cytopenia is triggered by CLL therapy, the guidelines recommended halting treatment and beginning immunosuppression.

The guideline development was supported by the British Society for Haematology. The UK CLL Forum is a registered charity that receives funding from a number of pharmaceutical companies.

SOURCE: Schuh AH et al. Br J Haematol. 2018 Jul 15. doi: 10.1111/bjh.15460.

Patients with chronic obstructive pulmonary disease with shorter telomere lengths in their peripheral white blood cells may be at greater risk of exacerbations and death, according to a study published in Chest.

U.S. Department of Energy

The evidence suggests that chronic obstructive pulmonary disease (COPD) may be a disease of accelerated aging, partly because of its relation to other senescence-related disorders such as osteoporosis and dementia, but also because it shows an exponential increase in prevalence in older age.

Telomere lengths are a measure of cellular senescence, and previous research has found that the telomeres are shortened in the peripheral leukocytes of patients with COPD, compared with healthy controls.

In this study, researchers examined the absolute telomere length of 576 people with moderate to severe COPD who were participating in the MACRO (Macrolide Azithromycin for Prevention of Exacerbations of COPD) study.

They found that individuals in the lowest quartile of telomere lengths had significantly worse health status and a higher exacerbation rate after accounting for treatment, compared with individuals in the higher quartile.

Patients with shorter telomere length had worse health status, as defined by higher St. George’s Respiratory Questionnaire scores. In the placebo arm of the study, the exacerbation rate (rate ratio, 1.50; 95% confidence interval, 1.16-1.95; P = .002) and mortality risk (hazard ratio, 9.45; 95% CI, 2.85-31.36; P = .015) were significantly higher in the shorter telomere group than in the longer telomere group; these differences were not observed in the azithromycin arm.

Patients with shorter telomeres also had a 800% higher risk of total mortality, compared with individuals with longer telomeres, although this was only evident in the placebo arm of the study, not the azithromycin arm. However, the authors noted that these data should be interpreted with caution because of the small number of deaths during the study.

“Together, these data support the notion that COPD is a systemic disease of accelerated aging and that replicative senescence, denoted by peripheral blood telomeres, is associated with poor health outcomes in COPD,” wrote Minhee Jin, of the University of British Columbia, Vancouver, and coauthors.

“It is now well established that replicative senescence results in a change of cellular phenotype to a proinflammatory state, a process that has been referred to as senescence-associated secretory phenotype,” they added.

The study also found that the median value for telomere length across the study participants – who had a mean age of 66 years – was equivalent to the expected value for someone in their 80s, “suggesting that on average MACRO participants were biologically much older than their chronological age.”

Researchers also noted that patients in the lowest quartile of telomere length had significantly lower forced vital capacity values, which suggested shorter telomeres could be a biomarker of restrictive physiology.

MACRO was funded by the U.S. National Heart, Lung, and Blood Institute, and the biomarker component of the study was funded by the Canadian Respiratory Research Network, Genome Canada, and the St. Paul’s Hospital Foundation. One author was an employee of GenomeDx Biosciences, three declared funding from or consultancies with the pharmaceutical industry. No other conflicts of interest were reported.

SOURCE: Jin M et al. Chest. 2018 Jul 12. doi: 10.1016/j.chest.2018.05.022.

Patients with chronic obstructive pulmonary disease with shorter telomere lengths in their peripheral white blood cells may be at greater risk of exacerbations and death, according to a study published in Chest.

U.S. Department of Energy

The evidence suggests that chronic obstructive pulmonary disease (COPD) may be a disease of accelerated aging, partly because of its relation to other senescence-related disorders such as osteoporosis and dementia, but also because it shows an exponential increase in prevalence in older age.

Telomere lengths are a measure of cellular senescence, and previous research has found that the telomeres are shortened in the peripheral leukocytes of patients with COPD, compared with healthy controls.

In this study, researchers examined the absolute telomere length of 576 people with moderate to severe COPD who were participating in the MACRO (Macrolide Azithromycin for Prevention of Exacerbations of COPD) study.

They found that individuals in the lowest quartile of telomere lengths had significantly worse health status and a higher exacerbation rate after accounting for treatment, compared with individuals in the higher quartile.

Patients with shorter telomere length had worse health status, as defined by higher St. George’s Respiratory Questionnaire scores. In the placebo arm of the study, the exacerbation rate (rate ratio, 1.50; 95% confidence interval, 1.16-1.95; P = .002) and mortality risk (hazard ratio, 9.45; 95% CI, 2.85-31.36; P = .015) were significantly higher in the shorter telomere group than in the longer telomere group; these differences were not observed in the azithromycin arm.

Patients with shorter telomeres also had a 800% higher risk of total mortality, compared with individuals with longer telomeres, although this was only evident in the placebo arm of the study, not the azithromycin arm. However, the authors noted that these data should be interpreted with caution because of the small number of deaths during the study.

“Together, these data support the notion that COPD is a systemic disease of accelerated aging and that replicative senescence, denoted by peripheral blood telomeres, is associated with poor health outcomes in COPD,” wrote Minhee Jin, of the University of British Columbia, Vancouver, and coauthors.

“It is now well established that replicative senescence results in a change of cellular phenotype to a proinflammatory state, a process that has been referred to as senescence-associated secretory phenotype,” they added.

The study also found that the median value for telomere length across the study participants – who had a mean age of 66 years – was equivalent to the expected value for someone in their 80s, “suggesting that on average MACRO participants were biologically much older than their chronological age.”

Researchers also noted that patients in the lowest quartile of telomere length had significantly lower forced vital capacity values, which suggested shorter telomeres could be a biomarker of restrictive physiology.

MACRO was funded by the U.S. National Heart, Lung, and Blood Institute, and the biomarker component of the study was funded by the Canadian Respiratory Research Network, Genome Canada, and the St. Paul’s Hospital Foundation. One author was an employee of GenomeDx Biosciences, three declared funding from or consultancies with the pharmaceutical industry. No other conflicts of interest were reported.

SOURCE: Jin M et al. Chest. 2018 Jul 12. doi: 10.1016/j.chest.2018.05.022.

Patients with chronic obstructive pulmonary disease with shorter telomere lengths in their peripheral white blood cells may be at greater risk of exacerbations and death, according to a study published in Chest.

U.S. Department of Energy

The evidence suggests that chronic obstructive pulmonary disease (COPD) may be a disease of accelerated aging, partly because of its relation to other senescence-related disorders such as osteoporosis and dementia, but also because it shows an exponential increase in prevalence in older age.

Telomere lengths are a measure of cellular senescence, and previous research has found that the telomeres are shortened in the peripheral leukocytes of patients with COPD, compared with healthy controls.

In this study, researchers examined the absolute telomere length of 576 people with moderate to severe COPD who were participating in the MACRO (Macrolide Azithromycin for Prevention of Exacerbations of COPD) study.

They found that individuals in the lowest quartile of telomere lengths had significantly worse health status and a higher exacerbation rate after accounting for treatment, compared with individuals in the higher quartile.

Patients with shorter telomere length had worse health status, as defined by higher St. George’s Respiratory Questionnaire scores. In the placebo arm of the study, the exacerbation rate (rate ratio, 1.50; 95% confidence interval, 1.16-1.95; P = .002) and mortality risk (hazard ratio, 9.45; 95% CI, 2.85-31.36; P = .015) were significantly higher in the shorter telomere group than in the longer telomere group; these differences were not observed in the azithromycin arm.

Patients with shorter telomeres also had a 800% higher risk of total mortality, compared with individuals with longer telomeres, although this was only evident in the placebo arm of the study, not the azithromycin arm. However, the authors noted that these data should be interpreted with caution because of the small number of deaths during the study.

“Together, these data support the notion that COPD is a systemic disease of accelerated aging and that replicative senescence, denoted by peripheral blood telomeres, is associated with poor health outcomes in COPD,” wrote Minhee Jin, of the University of British Columbia, Vancouver, and coauthors.

“It is now well established that replicative senescence results in a change of cellular phenotype to a proinflammatory state, a process that has been referred to as senescence-associated secretory phenotype,” they added.

The study also found that the median value for telomere length across the study participants – who had a mean age of 66 years – was equivalent to the expected value for someone in their 80s, “suggesting that on average MACRO participants were biologically much older than their chronological age.”

Researchers also noted that patients in the lowest quartile of telomere length had significantly lower forced vital capacity values, which suggested shorter telomeres could be a biomarker of restrictive physiology.

MACRO was funded by the U.S. National Heart, Lung, and Blood Institute, and the biomarker component of the study was funded by the Canadian Respiratory Research Network, Genome Canada, and the St. Paul’s Hospital Foundation. One author was an employee of GenomeDx Biosciences, three declared funding from or consultancies with the pharmaceutical industry. No other conflicts of interest were reported.

SOURCE: Jin M et al. Chest. 2018 Jul 12. doi: 10.1016/j.chest.2018.05.022.

The only 2 medicines currently approved for young people with type 2 diabetes—long-acting insulin and metformin—do not slow the progression of diabetes in young people, according to a study funded in part by the National Institute of Diabetes and Digestive and Kidney Diseases.

A substudy of the Restoring Insulin Secretion (RISE) study, the RISE Pediatric Medication Study looked at the effects of insulin and metformin in 91 patients aged 10 to 19 years. The participants were randomly assigned to 1 of 2 treatment groups. The first received 3 months of glargine, a long-acting insulin, followed by 9 months of metformin. The second group received only metformin for 12 months. The participants were followed for 3 more months after treatment ended. The pediatric study found that beta-cell function declined in both groups during treatment and worsened after treatment ended.

Researchers also compared the pediatric participants with their adult counterparts in 2 other RISE trials and found the young people had more insulin resistance and other signs of disease progression at the same stage in the disease. Moreover, at baseline, the younger patients responded to the severe insulin resistance with a greater insulin response than did the adults, which the researchers say may be a reason for their more rapid loss of beta-cell function.

However, the study also found modest improvement in blood glucose with metformin in both groups. But metformin alone is not a long-term solution for many youth, said Dr. Kristen Nadeau, principal investigator for the pediatric study. Their findings underscore the “urgent and growing need,” she says, for more options.

The only 2 medicines currently approved for young people with type 2 diabetes—long-acting insulin and metformin—do not slow the progression of diabetes in young people, according to a study funded in part by the National Institute of Diabetes and Digestive and Kidney Diseases.

A substudy of the Restoring Insulin Secretion (RISE) study, the RISE Pediatric Medication Study looked at the effects of insulin and metformin in 91 patients aged 10 to 19 years. The participants were randomly assigned to 1 of 2 treatment groups. The first received 3 months of glargine, a long-acting insulin, followed by 9 months of metformin. The second group received only metformin for 12 months. The participants were followed for 3 more months after treatment ended. The pediatric study found that beta-cell function declined in both groups during treatment and worsened after treatment ended.

Researchers also compared the pediatric participants with their adult counterparts in 2 other RISE trials and found the young people had more insulin resistance and other signs of disease progression at the same stage in the disease. Moreover, at baseline, the younger patients responded to the severe insulin resistance with a greater insulin response than did the adults, which the researchers say may be a reason for their more rapid loss of beta-cell function.

However, the study also found modest improvement in blood glucose with metformin in both groups. But metformin alone is not a long-term solution for many youth, said Dr. Kristen Nadeau, principal investigator for the pediatric study. Their findings underscore the “urgent and growing need,” she says, for more options.

The only 2 medicines currently approved for young people with type 2 diabetes—long-acting insulin and metformin—do not slow the progression of diabetes in young people, according to a study funded in part by the National Institute of Diabetes and Digestive and Kidney Diseases.

A substudy of the Restoring Insulin Secretion (RISE) study, the RISE Pediatric Medication Study looked at the effects of insulin and metformin in 91 patients aged 10 to 19 years. The participants were randomly assigned to 1 of 2 treatment groups. The first received 3 months of glargine, a long-acting insulin, followed by 9 months of metformin. The second group received only metformin for 12 months. The participants were followed for 3 more months after treatment ended. The pediatric study found that beta-cell function declined in both groups during treatment and worsened after treatment ended.

Researchers also compared the pediatric participants with their adult counterparts in 2 other RISE trials and found the young people had more insulin resistance and other signs of disease progression at the same stage in the disease. Moreover, at baseline, the younger patients responded to the severe insulin resistance with a greater insulin response than did the adults, which the researchers say may be a reason for their more rapid loss of beta-cell function.

However, the study also found modest improvement in blood glucose with metformin in both groups. But metformin alone is not a long-term solution for many youth, said Dr. Kristen Nadeau, principal investigator for the pediatric study. Their findings underscore the “urgent and growing need,” she says, for more options.

Many patients with primary central nervous system lymphoma (PCNSL) experience rapid, aggressive progression of CNS malignancy. It is “accepted,” say researchers from Chonnam National University Hwasun Hospital in the Republic of Korea, that salvage therapy is beneficial and significantly improves survival in comparison to palliative care, but therapy options remain limited—mainly because few trials have been done. Several case reports have suggested that bendamustine has modest clinical activity against relapsed PCNSL, the researchers note, but its effect as part of combination salvage therapy in these patients has not been established. The study offers some validation of previous findings and new information about the benefits of a bendamustine-based combination regimen.

The researchers enrolled 10 patients, of whom 7 had refractory disease. All had previously been on high-dose methotrexate. Of the 3 relapsed patients, 1 entered the study at second relapse. The patients received either R-B(O)AD or R-BAD (rituximab, vincristine, bendamustine, cytarabine, dexamethasone) every 4 weeks for up to 4 cycles. Vincristine was omitted in 4 regimens, and dosages of bendamustine and cytarabine were reduced for 4 patients who were over 70.

The overall response rate for R-B(O)AD was 50%. One patient achieved complete response and 4 achieved partial response. The researchers observed “remarkable effects” on imaging in patients who responded. They attribute the activity to the anticipated synergy of bendamustine combined with cytarabine—even though disease in the majority of the patients had progressed despite previous treatment with cytarabine.

However, the synergistic effects also led to significant marrow depression; hematologic toxicity with R-B(O)AD was “considerable,” with grade 3 or 4 neutropenia and thrombocytopenia seen in more than 85% of treatment cycles. Moreover, 3 patients developed severe infection, all with involvement of the lungs. The researchers therefore amended the study protocol to reduce cytarabine dosage. While the toxicity is significant, the researchers say, it is manageable with the dose reduction and supportive care.

Bendamustine cerebrospinal fluid levels were minimal, but corresponded to plasma exposure and response to treatment in deep tumor locations.

Although the study is small, it supports the use of the bendamustine-based regimen as an effective salvage option, the researchers conclude, especially for patients who are no longer responding to methotrexate or have developed cumulative renal or neurotoxicity from treatment.

Source:
Kim T, Choi HY, Lee HS, et al. BMC Cancer. 2018;18(1):729

Many patients with primary central nervous system lymphoma (PCNSL) experience rapid, aggressive progression of CNS malignancy. It is “accepted,” say researchers from Chonnam National University Hwasun Hospital in the Republic of Korea, that salvage therapy is beneficial and significantly improves survival in comparison to palliative care, but therapy options remain limited—mainly because few trials have been done. Several case reports have suggested that bendamustine has modest clinical activity against relapsed PCNSL, the researchers note, but its effect as part of combination salvage therapy in these patients has not been established. The study offers some validation of previous findings and new information about the benefits of a bendamustine-based combination regimen.

The researchers enrolled 10 patients, of whom 7 had refractory disease. All had previously been on high-dose methotrexate. Of the 3 relapsed patients, 1 entered the study at second relapse. The patients received either R-B(O)AD or R-BAD (rituximab, vincristine, bendamustine, cytarabine, dexamethasone) every 4 weeks for up to 4 cycles. Vincristine was omitted in 4 regimens, and dosages of bendamustine and cytarabine were reduced for 4 patients who were over 70.

The overall response rate for R-B(O)AD was 50%. One patient achieved complete response and 4 achieved partial response. The researchers observed “remarkable effects” on imaging in patients who responded. They attribute the activity to the anticipated synergy of bendamustine combined with cytarabine—even though disease in the majority of the patients had progressed despite previous treatment with cytarabine.

However, the synergistic effects also led to significant marrow depression; hematologic toxicity with R-B(O)AD was “considerable,” with grade 3 or 4 neutropenia and thrombocytopenia seen in more than 85% of treatment cycles. Moreover, 3 patients developed severe infection, all with involvement of the lungs. The researchers therefore amended the study protocol to reduce cytarabine dosage. While the toxicity is significant, the researchers say, it is manageable with the dose reduction and supportive care.

Bendamustine cerebrospinal fluid levels were minimal, but corresponded to plasma exposure and response to treatment in deep tumor locations.

Although the study is small, it supports the use of the bendamustine-based regimen as an effective salvage option, the researchers conclude, especially for patients who are no longer responding to methotrexate or have developed cumulative renal or neurotoxicity from treatment.

Source:
Kim T, Choi HY, Lee HS, et al. BMC Cancer. 2018;18(1):729

Many patients with primary central nervous system lymphoma (PCNSL) experience rapid, aggressive progression of CNS malignancy. It is “accepted,” say researchers from Chonnam National University Hwasun Hospital in the Republic of Korea, that salvage therapy is beneficial and significantly improves survival in comparison to palliative care, but therapy options remain limited—mainly because few trials have been done. Several case reports have suggested that bendamustine has modest clinical activity against relapsed PCNSL, the researchers note, but its effect as part of combination salvage therapy in these patients has not been established. The study offers some validation of previous findings and new information about the benefits of a bendamustine-based combination regimen.

The researchers enrolled 10 patients, of whom 7 had refractory disease. All had previously been on high-dose methotrexate. Of the 3 relapsed patients, 1 entered the study at second relapse. The patients received either R-B(O)AD or R-BAD (rituximab, vincristine, bendamustine, cytarabine, dexamethasone) every 4 weeks for up to 4 cycles. Vincristine was omitted in 4 regimens, and dosages of bendamustine and cytarabine were reduced for 4 patients who were over 70.

The overall response rate for R-B(O)AD was 50%. One patient achieved complete response and 4 achieved partial response. The researchers observed “remarkable effects” on imaging in patients who responded. They attribute the activity to the anticipated synergy of bendamustine combined with cytarabine—even though disease in the majority of the patients had progressed despite previous treatment with cytarabine.

However, the synergistic effects also led to significant marrow depression; hematologic toxicity with R-B(O)AD was “considerable,” with grade 3 or 4 neutropenia and thrombocytopenia seen in more than 85% of treatment cycles. Moreover, 3 patients developed severe infection, all with involvement of the lungs. The researchers therefore amended the study protocol to reduce cytarabine dosage. While the toxicity is significant, the researchers say, it is manageable with the dose reduction and supportive care.

Bendamustine cerebrospinal fluid levels were minimal, but corresponded to plasma exposure and response to treatment in deep tumor locations.

Although the study is small, it supports the use of the bendamustine-based regimen as an effective salvage option, the researchers conclude, especially for patients who are no longer responding to methotrexate or have developed cumulative renal or neurotoxicity from treatment.

Source:
Kim T, Choi HY, Lee HS, et al. BMC Cancer. 2018;18(1):729

Having health insurance can mean the difference between life and death for patients with follicular lymphoma, suggest results of a study showing that patients with private health insurance had nearly twofold better survival outcomes than patients without insurance or those who were covered by Medicare or Medicaid.

Thinkstock

A review of records on more than 43,000 patients with follicular lymphoma (FL) in a national cancer registry showed that, compared with patients under age 65 with private insurance, the hazard ratios (HR) for death among patients in the same age bracket with either no insurance, Medicaid, or Medicare were, respectively, 1.96, 1.83, and 1.96 (P less than .0001 for each comparison).

“Our study finds that insurance status contributes to survival disparities in FL. Future studies on outcomes in FL should include insurance status as an important predictor,” Christopher R. Flowers, MD, of Emory University in Atlanta and his colleagues wrote in Blood.

“Further research on prognosis for FL should examine the impact of public policy, such as the passage of the [Affordable Care Act], on FL outcomes, as well as examine other factors that influence access to care, such as individual-level socioeconomic status, regular primary care visits, access to prescription medications, and care affordability,” they added.

The investigators noted that earlier research found that patients with Medicaid or no insurance were more likely than privately-insured patients to be diagnosed with cancers at advanced stages, and that some patients with aggressive non-Hodgkin lymphomas have been shown to have insurance-related disparities in treatments and outcomes.

To see whether the same could be true for patients with indolent-histology lymphomas such as FL, they extracted data from the National Cancer Database, a nationwide hospital-based cancer registry sponsored jointly by the American College of Surgeons and the American Cancer Society.

They identified a total of 43,648 patients aged 18 years or older who were diagnosed with FL from 2004 through 2014. They looked at both patients 18-64 years and those 65 years and older to account for changes in insurance with Medicare eligibility.

Overall survival among patients younger than age 65 was significantly worse for patients with public insurance (Medicaid or Medicare) or no insurance in Cox proportional hazard models controlling for available data on sociodemographic factors and prognostic indicators.

However, compared with patients aged 65 and older with private insurance, only patients with Medicare as their sole source of insurance had significantly worse overall survival (HR, 1.28; P less than .0001).

Patients who were uninsured or had Medicaid were more likely than others to have lower socioeconomic status, present with advanced-stage disease, have systemic symptoms, and have multiple comorbidities that persisted after controlling for known sociodemographic and prognostic factors.

The investigators found that, among patients under age 65, those with a comorbidity score of 1 had an HR for death of 1.71, compared with patients with no comorbidities, and that patients with a score of 2 or greater had a HR of 3.1 (P less than .0001 for each comparison).

“The findings of the study indicate that improving access to affordable, quality health care may reduce disparities in survival for those currently lacking coverage,” the investigators wrote.

The study was supported by Emory University, the National Institutes of Health, and the National Center for Advancing Translational Sciences. Dr. Flowers reported financial relationships with AbbVie, Spectrum, Celgene, and several other companies. The other authors reported having nothing to disclose.

SOURCE: Goldstein JS et al. Blood. 2018 Jul 24. doi: 10.1182/blood-2018-03-839035.

Having health insurance can mean the difference between life and death for patients with follicular lymphoma, suggest results of a study showing that patients with private health insurance had nearly twofold better survival outcomes than patients without insurance or those who were covered by Medicare or Medicaid.

Thinkstock

A review of records on more than 43,000 patients with follicular lymphoma (FL) in a national cancer registry showed that, compared with patients under age 65 with private insurance, the hazard ratios (HR) for death among patients in the same age bracket with either no insurance, Medicaid, or Medicare were, respectively, 1.96, 1.83, and 1.96 (P less than .0001 for each comparison).

“Our study finds that insurance status contributes to survival disparities in FL. Future studies on outcomes in FL should include insurance status as an important predictor,” Christopher R. Flowers, MD, of Emory University in Atlanta and his colleagues wrote in Blood.

“Further research on prognosis for FL should examine the impact of public policy, such as the passage of the [Affordable Care Act], on FL outcomes, as well as examine other factors that influence access to care, such as individual-level socioeconomic status, regular primary care visits, access to prescription medications, and care affordability,” they added.

The investigators noted that earlier research found that patients with Medicaid or no insurance were more likely than privately-insured patients to be diagnosed with cancers at advanced stages, and that some patients with aggressive non-Hodgkin lymphomas have been shown to have insurance-related disparities in treatments and outcomes.

To see whether the same could be true for patients with indolent-histology lymphomas such as FL, they extracted data from the National Cancer Database, a nationwide hospital-based cancer registry sponsored jointly by the American College of Surgeons and the American Cancer Society.

They identified a total of 43,648 patients aged 18 years or older who were diagnosed with FL from 2004 through 2014. They looked at both patients 18-64 years and those 65 years and older to account for changes in insurance with Medicare eligibility.

Overall survival among patients younger than age 65 was significantly worse for patients with public insurance (Medicaid or Medicare) or no insurance in Cox proportional hazard models controlling for available data on sociodemographic factors and prognostic indicators.

However, compared with patients aged 65 and older with private insurance, only patients with Medicare as their sole source of insurance had significantly worse overall survival (HR, 1.28; P less than .0001).

Patients who were uninsured or had Medicaid were more likely than others to have lower socioeconomic status, present with advanced-stage disease, have systemic symptoms, and have multiple comorbidities that persisted after controlling for known sociodemographic and prognostic factors.

The investigators found that, among patients under age 65, those with a comorbidity score of 1 had an HR for death of 1.71, compared with patients with no comorbidities, and that patients with a score of 2 or greater had a HR of 3.1 (P less than .0001 for each comparison).

“The findings of the study indicate that improving access to affordable, quality health care may reduce disparities in survival for those currently lacking coverage,” the investigators wrote.

The study was supported by Emory University, the National Institutes of Health, and the National Center for Advancing Translational Sciences. Dr. Flowers reported financial relationships with AbbVie, Spectrum, Celgene, and several other companies. The other authors reported having nothing to disclose.

SOURCE: Goldstein JS et al. Blood. 2018 Jul 24. doi: 10.1182/blood-2018-03-839035.

Having health insurance can mean the difference between life and death for patients with follicular lymphoma, suggest results of a study showing that patients with private health insurance had nearly twofold better survival outcomes than patients without insurance or those who were covered by Medicare or Medicaid.

Thinkstock

A review of records on more than 43,000 patients with follicular lymphoma (FL) in a national cancer registry showed that, compared with patients under age 65 with private insurance, the hazard ratios (HR) for death among patients in the same age bracket with either no insurance, Medicaid, or Medicare were, respectively, 1.96, 1.83, and 1.96 (P less than .0001 for each comparison).

“Our study finds that insurance status contributes to survival disparities in FL. Future studies on outcomes in FL should include insurance status as an important predictor,” Christopher R. Flowers, MD, of Emory University in Atlanta and his colleagues wrote in Blood.

“Further research on prognosis for FL should examine the impact of public policy, such as the passage of the [Affordable Care Act], on FL outcomes, as well as examine other factors that influence access to care, such as individual-level socioeconomic status, regular primary care visits, access to prescription medications, and care affordability,” they added.

The investigators noted that earlier research found that patients with Medicaid or no insurance were more likely than privately-insured patients to be diagnosed with cancers at advanced stages, and that some patients with aggressive non-Hodgkin lymphomas have been shown to have insurance-related disparities in treatments and outcomes.

To see whether the same could be true for patients with indolent-histology lymphomas such as FL, they extracted data from the National Cancer Database, a nationwide hospital-based cancer registry sponsored jointly by the American College of Surgeons and the American Cancer Society.

They identified a total of 43,648 patients aged 18 years or older who were diagnosed with FL from 2004 through 2014. They looked at both patients 18-64 years and those 65 years and older to account for changes in insurance with Medicare eligibility.

Overall survival among patients younger than age 65 was significantly worse for patients with public insurance (Medicaid or Medicare) or no insurance in Cox proportional hazard models controlling for available data on sociodemographic factors and prognostic indicators.

However, compared with patients aged 65 and older with private insurance, only patients with Medicare as their sole source of insurance had significantly worse overall survival (HR, 1.28; P less than .0001).

Patients who were uninsured or had Medicaid were more likely than others to have lower socioeconomic status, present with advanced-stage disease, have systemic symptoms, and have multiple comorbidities that persisted after controlling for known sociodemographic and prognostic factors.

The investigators found that, among patients under age 65, those with a comorbidity score of 1 had an HR for death of 1.71, compared with patients with no comorbidities, and that patients with a score of 2 or greater had a HR of 3.1 (P less than .0001 for each comparison).

“The findings of the study indicate that improving access to affordable, quality health care may reduce disparities in survival for those currently lacking coverage,” the investigators wrote.

The study was supported by Emory University, the National Institutes of Health, and the National Center for Advancing Translational Sciences. Dr. Flowers reported financial relationships with AbbVie, Spectrum, Celgene, and several other companies. The other authors reported having nothing to disclose.

SOURCE: Goldstein JS et al. Blood. 2018 Jul 24. doi: 10.1182/blood-2018-03-839035.

Indian Health Service (IHS) is taking applications for students to “take part in enriching projects to further the IHS mission of raising the physical, mental, social, and spiritual health of American Indians and Alaska Natives to the highest level.” The twist? The students can do it remotely.

The IHS is a new partner with the Virtual Federal Service, the largest virtual internship program in the world, making it the 31st federal agency to participate. Other agencies include the Peace Corps and The National Aeronautics and Space Administration.

The “einterns” spend 10 hours a week from September through May working remotely. The work is unpaid, although they may get course credit. For some, it is the first time they have worked on issues affecting Native people. Those projects have included producing bilingual Navajo and English videos for rural health clinics, developing Navajo-specific health education materials on palliative care, creating a sexual assault locator map, and creating social media strategies and campaigns for health promotion.

IHS welcomed more than 15 interns, both undergraduates and graduate students, for the 2017-2018 academic year.

Indian Health Service (IHS) is taking applications for students to “take part in enriching projects to further the IHS mission of raising the physical, mental, social, and spiritual health of American Indians and Alaska Natives to the highest level.” The twist? The students can do it remotely.

The IHS is a new partner with the Virtual Federal Service, the largest virtual internship program in the world, making it the 31st federal agency to participate. Other agencies include the Peace Corps and The National Aeronautics and Space Administration.

The “einterns” spend 10 hours a week from September through May working remotely. The work is unpaid, although they may get course credit. For some, it is the first time they have worked on issues affecting Native people. Those projects have included producing bilingual Navajo and English videos for rural health clinics, developing Navajo-specific health education materials on palliative care, creating a sexual assault locator map, and creating social media strategies and campaigns for health promotion.

IHS welcomed more than 15 interns, both undergraduates and graduate students, for the 2017-2018 academic year.

Indian Health Service (IHS) is taking applications for students to “take part in enriching projects to further the IHS mission of raising the physical, mental, social, and spiritual health of American Indians and Alaska Natives to the highest level.” The twist? The students can do it remotely.

The IHS is a new partner with the Virtual Federal Service, the largest virtual internship program in the world, making it the 31st federal agency to participate. Other agencies include the Peace Corps and The National Aeronautics and Space Administration.

The “einterns” spend 10 hours a week from September through May working remotely. The work is unpaid, although they may get course credit. For some, it is the first time they have worked on issues affecting Native people. Those projects have included producing bilingual Navajo and English videos for rural health clinics, developing Navajo-specific health education materials on palliative care, creating a sexual assault locator map, and creating social media strategies and campaigns for health promotion.

IHS welcomed more than 15 interns, both undergraduates and graduate students, for the 2017-2018 academic year.

Bone marrow involvement in mantle cell lymphoma could be assessed using just ¹⁸fluorodeoxyglucose (FDG)–PET/CT, according to findings from a small, retrospective study published in Clinical Lymphoma, Myeloma & Leukemia.

Brudersohn/CC BY-SA 3.0/Wikimedia Commons

Rustain Morgan, MD, of the University of Colorado, Aurora, and his colleagues found that, at a certain threshold of bone marrow voxels in standard uptake value (SUV), there was 100% sensitivity and 80% specificity in determining bone marrow involvement in mantle cell lymphoma (MCL).

Currently, National Comprehensive Cancer Network guidelines call for bone marrow biopsy and whole body FDG PET/CT scan to complete an initial diagnosis of MCL.

“One of the most important factors for correct staging is the identification of bone marrow involvement, occurring in approximately 55% of patients with MCL, which classifies patients as advanced stage. However, accurate analysis of bone marrow involvement can be challenging due to sampling error,” the researchers wrote. “While bone marrow biopsy remains the gold standard, it is not a perfect standard given unilateral variability.”

In previous studies, FDG PET/CT was not considered sensitive enough to detect gastrointestinal or bone marrow involvement. However, these earlier studies used SUV maximum or mean or a visual assessment of the bone marrow activity, compared with hepatic uptake. To address this issue, the researchers developed a new method of examining SUV distribution throughout the pelvic bones by analyzing thousands of bone marrow voxels within the bilateral iliacs.

During the developmental phase, an institutional dataset of 11 patients with MCL was used to define the voxel-based analysis. These patients had undergone both unilateral iliac bone marrow biopsy and FDG PET/CT at the initial diagnosis. Then, FDG PET/CT scans from another 12 patients with MCL from a different institution were used to validate the developmental phase findings. Finally, a control group of 5 people with no known malignancy were referred for FDG PET/CT pulmonary nodule evaluation.

“The hypothesis of the study was that, if the bone marrow was involved by lymphoma, then there would be a small increase in the SUV of each voxel, reflecting involvement by the lymphoma. In order to capture such changes, we analyzed the percent of total voxels in SUV ranging from 0.75 to 1.20, in increments of 0.05, as this is where the greatest divergence was visually identified,” the researchers wrote. “The goal was to identify if a percentage of voxels at a set SUV could detect lymphomatous involvement.”

The researchers identified 10 candidate thresholds in the developmental phase; 4 of these performed better than the others in the validation phase. Using those thresholds, 10 of the 12 patients in the validation cohort could be correctly staged using FDG PET/CT.

Further analysis identified a single threshold that performed best: If greater than 38% of the voxels (averaging 1,734 voxels) demonstrated an SUV of less than 0.95, the sensitivity was 100% and the specificity was 80%.

The researchers acknowledged that the findings are limited because of the study’s small sample size and said the results should be validated in a larger trial.

There was no external funding for the study and the researchers reported having no financial disclosures.

mschneider@mdedge.com

SOURCE: Morgan R et al. Clin Lymphoma Myeloma Leuk. 2018 Jul 4. doi: 10.1016/j.clml.2018.06.024.

Bone marrow involvement in mantle cell lymphoma could be assessed using just ¹⁸fluorodeoxyglucose (FDG)–PET/CT, according to findings from a small, retrospective study published in Clinical Lymphoma, Myeloma & Leukemia.

Brudersohn/CC BY-SA 3.0/Wikimedia Commons

Rustain Morgan, MD, of the University of Colorado, Aurora, and his colleagues found that, at a certain threshold of bone marrow voxels in standard uptake value (SUV), there was 100% sensitivity and 80% specificity in determining bone marrow involvement in mantle cell lymphoma (MCL).

Currently, National Comprehensive Cancer Network guidelines call for bone marrow biopsy and whole body FDG PET/CT scan to complete an initial diagnosis of MCL.

“One of the most important factors for correct staging is the identification of bone marrow involvement, occurring in approximately 55% of patients with MCL, which classifies patients as advanced stage. However, accurate analysis of bone marrow involvement can be challenging due to sampling error,” the researchers wrote. “While bone marrow biopsy remains the gold standard, it is not a perfect standard given unilateral variability.”

In previous studies, FDG PET/CT was not considered sensitive enough to detect gastrointestinal or bone marrow involvement. However, these earlier studies used SUV maximum or mean or a visual assessment of the bone marrow activity, compared with hepatic uptake. To address this issue, the researchers developed a new method of examining SUV distribution throughout the pelvic bones by analyzing thousands of bone marrow voxels within the bilateral iliacs.

During the developmental phase, an institutional dataset of 11 patients with MCL was used to define the voxel-based analysis. These patients had undergone both unilateral iliac bone marrow biopsy and FDG PET/CT at the initial diagnosis. Then, FDG PET/CT scans from another 12 patients with MCL from a different institution were used to validate the developmental phase findings. Finally, a control group of 5 people with no known malignancy were referred for FDG PET/CT pulmonary nodule evaluation.

“The hypothesis of the study was that, if the bone marrow was involved by lymphoma, then there would be a small increase in the SUV of each voxel, reflecting involvement by the lymphoma. In order to capture such changes, we analyzed the percent of total voxels in SUV ranging from 0.75 to 1.20, in increments of 0.05, as this is where the greatest divergence was visually identified,” the researchers wrote. “The goal was to identify if a percentage of voxels at a set SUV could detect lymphomatous involvement.”

The researchers identified 10 candidate thresholds in the developmental phase; 4 of these performed better than the others in the validation phase. Using those thresholds, 10 of the 12 patients in the validation cohort could be correctly staged using FDG PET/CT.

Further analysis identified a single threshold that performed best: If greater than 38% of the voxels (averaging 1,734 voxels) demonstrated an SUV of less than 0.95, the sensitivity was 100% and the specificity was 80%.

The researchers acknowledged that the findings are limited because of the study’s small sample size and said the results should be validated in a larger trial.

There was no external funding for the study and the researchers reported having no financial disclosures.

mschneider@mdedge.com

SOURCE: Morgan R et al. Clin Lymphoma Myeloma Leuk. 2018 Jul 4. doi: 10.1016/j.clml.2018.06.024.

Bone marrow involvement in mantle cell lymphoma could be assessed using just ¹⁸fluorodeoxyglucose (FDG)–PET/CT, according to findings from a small, retrospective study published in Clinical Lymphoma, Myeloma & Leukemia.

Brudersohn/CC BY-SA 3.0/Wikimedia Commons

Rustain Morgan, MD, of the University of Colorado, Aurora, and his colleagues found that, at a certain threshold of bone marrow voxels in standard uptake value (SUV), there was 100% sensitivity and 80% specificity in determining bone marrow involvement in mantle cell lymphoma (MCL).

Currently, National Comprehensive Cancer Network guidelines call for bone marrow biopsy and whole body FDG PET/CT scan to complete an initial diagnosis of MCL.

“One of the most important factors for correct staging is the identification of bone marrow involvement, occurring in approximately 55% of patients with MCL, which classifies patients as advanced stage. However, accurate analysis of bone marrow involvement can be challenging due to sampling error,” the researchers wrote. “While bone marrow biopsy remains the gold standard, it is not a perfect standard given unilateral variability.”

In previous studies, FDG PET/CT was not considered sensitive enough to detect gastrointestinal or bone marrow involvement. However, these earlier studies used SUV maximum or mean or a visual assessment of the bone marrow activity, compared with hepatic uptake. To address this issue, the researchers developed a new method of examining SUV distribution throughout the pelvic bones by analyzing thousands of bone marrow voxels within the bilateral iliacs.

During the developmental phase, an institutional dataset of 11 patients with MCL was used to define the voxel-based analysis. These patients had undergone both unilateral iliac bone marrow biopsy and FDG PET/CT at the initial diagnosis. Then, FDG PET/CT scans from another 12 patients with MCL from a different institution were used to validate the developmental phase findings. Finally, a control group of 5 people with no known malignancy were referred for FDG PET/CT pulmonary nodule evaluation.

“The hypothesis of the study was that, if the bone marrow was involved by lymphoma, then there would be a small increase in the SUV of each voxel, reflecting involvement by the lymphoma. In order to capture such changes, we analyzed the percent of total voxels in SUV ranging from 0.75 to 1.20, in increments of 0.05, as this is where the greatest divergence was visually identified,” the researchers wrote. “The goal was to identify if a percentage of voxels at a set SUV could detect lymphomatous involvement.”

The researchers identified 10 candidate thresholds in the developmental phase; 4 of these performed better than the others in the validation phase. Using those thresholds, 10 of the 12 patients in the validation cohort could be correctly staged using FDG PET/CT.

Further analysis identified a single threshold that performed best: If greater than 38% of the voxels (averaging 1,734 voxels) demonstrated an SUV of less than 0.95, the sensitivity was 100% and the specificity was 80%.

The researchers acknowledged that the findings are limited because of the study’s small sample size and said the results should be validated in a larger trial.

There was no external funding for the study and the researchers reported having no financial disclosures.

mschneider@mdedge.com

SOURCE: Morgan R et al. Clin Lymphoma Myeloma Leuk. 2018 Jul 4. doi: 10.1016/j.clml.2018.06.024.

Any economist could have predicted it: As the price of electronic cigarettes goes down, sales increase.

Price decreases for the three products available in 2012 were all significant: The average price per unit was down 48% for rechargeables by 2016, 14% for disposables, and 12% for prefilled cartridges. E-liquids were 9% cheaper by 2016, but that change did not reach significance, they noted.

“Overall, the increase in e-cigarette sales and decrease in price is consistent with previous studies demonstrating that e-cigarette sales are responsive to their own price changes. These trends suggest that, if e-cigarette prices continue to decrease, their sales may also continue to rise,” Dr. Wang and her associates wrote.

The data for the study came from the Nielsen Company and were based on retail sales at convenience stores; supermarkets; drug, dollar, and club stores; and military commissaries in the 48 contiguous states and Washington, D.C. One study limitation was the lack of data from tobacco/vape shops and the Internet.

rfranki@mdedge.com

SOURCE: Wang TW et al. Prev Chronic Dis. 2018;15:170555. doi: 10.5888/pcd15.170555.

Any economist could have predicted it: As the price of electronic cigarettes goes down, sales increase.

Price decreases for the three products available in 2012 were all significant: The average price per unit was down 48% for rechargeables by 2016, 14% for disposables, and 12% for prefilled cartridges. E-liquids were 9% cheaper by 2016, but that change did not reach significance, they noted.

“Overall, the increase in e-cigarette sales and decrease in price is consistent with previous studies demonstrating that e-cigarette sales are responsive to their own price changes. These trends suggest that, if e-cigarette prices continue to decrease, their sales may also continue to rise,” Dr. Wang and her associates wrote.

The data for the study came from the Nielsen Company and were based on retail sales at convenience stores; supermarkets; drug, dollar, and club stores; and military commissaries in the 48 contiguous states and Washington, D.C. One study limitation was the lack of data from tobacco/vape shops and the Internet.

rfranki@mdedge.com

SOURCE: Wang TW et al. Prev Chronic Dis. 2018;15:170555. doi: 10.5888/pcd15.170555.

Any economist could have predicted it: As the price of electronic cigarettes goes down, sales increase.

Price decreases for the three products available in 2012 were all significant: The average price per unit was down 48% for rechargeables by 2016, 14% for disposables, and 12% for prefilled cartridges. E-liquids were 9% cheaper by 2016, but that change did not reach significance, they noted.

“Overall, the increase in e-cigarette sales and decrease in price is consistent with previous studies demonstrating that e-cigarette sales are responsive to their own price changes. These trends suggest that, if e-cigarette prices continue to decrease, their sales may also continue to rise,” Dr. Wang and her associates wrote.

The data for the study came from the Nielsen Company and were based on retail sales at convenience stores; supermarkets; drug, dollar, and club stores; and military commissaries in the 48 contiguous states and Washington, D.C. One study limitation was the lack of data from tobacco/vape shops and the Internet.

rfranki@mdedge.com

SOURCE: Wang TW et al. Prev Chronic Dis. 2018;15:170555. doi: 10.5888/pcd15.170555.