User login
DOACs cut mortality
Results from the GARFIELD-AF study show that patients who are newly diagnosed with atrial fibrillation using a direct action anticoagulant led to benefits that tracked previously seen in randomized trials. Also today, the obesity paradox extends to PE patients, adjuvant flu vaccine reduces hospitalization in the oldest patients, and Tdap vaccination early in the third trimester of pregnancy raises antibodies in newborns.
Check out the MDedge Postcall podcast here:
Apple Podcasts
Google Podcasts
Results from the GARFIELD-AF study show that patients who are newly diagnosed with atrial fibrillation using a direct action anticoagulant led to benefits that tracked previously seen in randomized trials. Also today, the obesity paradox extends to PE patients, adjuvant flu vaccine reduces hospitalization in the oldest patients, and Tdap vaccination early in the third trimester of pregnancy raises antibodies in newborns.
Check out the MDedge Postcall podcast here:
Apple Podcasts
Google Podcasts
Results from the GARFIELD-AF study show that patients who are newly diagnosed with atrial fibrillation using a direct action anticoagulant led to benefits that tracked previously seen in randomized trials. Also today, the obesity paradox extends to PE patients, adjuvant flu vaccine reduces hospitalization in the oldest patients, and Tdap vaccination early in the third trimester of pregnancy raises antibodies in newborns.
Check out the MDedge Postcall podcast here:
Apple Podcasts
Google Podcasts
CT for evaluating pulmonary embolism overused
SAN ANTONIO – The recommended approach to evaluating suspected pulmonary embolism is “greatly underutilized” in the Veterans Health Administration system, Nancy Hsu, MD, said at the annual meeting of the American College of Chest Physicians.
Most Veterans Affairs sites did not require incorporation of a clinical decision rule (CDR) and highly sensitive D-dimer prior to ordering CT pulmonary angiography (CTPA) for suspected pulmonary embolism (PE), according to results of a survey by Dr. Hsu and her coinvestigator, Guy Soo Hoo, MD.
While CTPA has become the imaging modality of choice for evaluating suspected PE, it is overused and potentially avoidable in one-third of cases, said Dr. Hsu, who is with the VA Greater Los Angeles Healthcare System.
“In the 10 years following the advent of CTPA use, there was a 14-fold increase in usage, but there was no change in mortality,” Dr. Hsu said. “This is consistent with overdiagnosis.”
Dr. Hsu said.
Dr. Hsu and Dr. Soo Hoo surveyed 606 individuals at 18 Veterans Integrated Service Networks (VISNs) and 143 medical centers. A total of 120 fully completed questionnaires were analyzed.
Most respondents (63%) were chiefs, and 80% had 11+ years of experience, Dr. Hsu reported.
Almost all respondents (85%) said CDR with or without D-dimer was not required before ordering a CTPA, survey results show, while only about 7% required both.
“A very small minority of [Veterans Integrated Service Networks], or geographic regions, contained even one hospital that adhered to the guidelines,” Dr. Hsu added.
Though further analysis was limited by sample size, the average CTPA yield for PE appeared to be higher when both components were used in the evaluation, according to Dr. Hsu, who noted an 11.9% yield for CDR plus D-dimer.
Use of CTPA appeared lower at sites with CDR and D-dimer testing, Dr. Hsu added.
These results suggest a need for further research to compare CTPA use and yield in sites that have the algorithm in place, Dr. Hsu told attendees at the meeting.
Adherence to the CDR plus D-dimer diagnostic strategy is “modest at best” despite being a Top 5 Choosing Wisely recommendation in pulmonary medicine, Dr. Hsu told attendees.
The biggest barrier to optimal practice may be the fear of having a patient who “falls through the cracks” based on false-negative CDR and D-dimer data, according to Dr. Hsu.
On the other hand, judicious use of CTPA likely avoids negative sequelae related to radiation, contrast exposure, and treatment-related bleeding, Dr. Hsu said.
“It’s all about balancing risks and benefits,” she said from the podium in a discussion of the study results.
Dr. Hsu and Dr. Soo Hoo disclosed that they had no relationships relevant to their research.
SOURCE: Hsu N et al. CHEST. 2018 Oct. doi: 10.1016/j.chest.2018.08.937
SAN ANTONIO – The recommended approach to evaluating suspected pulmonary embolism is “greatly underutilized” in the Veterans Health Administration system, Nancy Hsu, MD, said at the annual meeting of the American College of Chest Physicians.
Most Veterans Affairs sites did not require incorporation of a clinical decision rule (CDR) and highly sensitive D-dimer prior to ordering CT pulmonary angiography (CTPA) for suspected pulmonary embolism (PE), according to results of a survey by Dr. Hsu and her coinvestigator, Guy Soo Hoo, MD.
While CTPA has become the imaging modality of choice for evaluating suspected PE, it is overused and potentially avoidable in one-third of cases, said Dr. Hsu, who is with the VA Greater Los Angeles Healthcare System.
“In the 10 years following the advent of CTPA use, there was a 14-fold increase in usage, but there was no change in mortality,” Dr. Hsu said. “This is consistent with overdiagnosis.”
Dr. Hsu said.
Dr. Hsu and Dr. Soo Hoo surveyed 606 individuals at 18 Veterans Integrated Service Networks (VISNs) and 143 medical centers. A total of 120 fully completed questionnaires were analyzed.
Most respondents (63%) were chiefs, and 80% had 11+ years of experience, Dr. Hsu reported.
Almost all respondents (85%) said CDR with or without D-dimer was not required before ordering a CTPA, survey results show, while only about 7% required both.
“A very small minority of [Veterans Integrated Service Networks], or geographic regions, contained even one hospital that adhered to the guidelines,” Dr. Hsu added.
Though further analysis was limited by sample size, the average CTPA yield for PE appeared to be higher when both components were used in the evaluation, according to Dr. Hsu, who noted an 11.9% yield for CDR plus D-dimer.
Use of CTPA appeared lower at sites with CDR and D-dimer testing, Dr. Hsu added.
These results suggest a need for further research to compare CTPA use and yield in sites that have the algorithm in place, Dr. Hsu told attendees at the meeting.
Adherence to the CDR plus D-dimer diagnostic strategy is “modest at best” despite being a Top 5 Choosing Wisely recommendation in pulmonary medicine, Dr. Hsu told attendees.
The biggest barrier to optimal practice may be the fear of having a patient who “falls through the cracks” based on false-negative CDR and D-dimer data, according to Dr. Hsu.
On the other hand, judicious use of CTPA likely avoids negative sequelae related to radiation, contrast exposure, and treatment-related bleeding, Dr. Hsu said.
“It’s all about balancing risks and benefits,” she said from the podium in a discussion of the study results.
Dr. Hsu and Dr. Soo Hoo disclosed that they had no relationships relevant to their research.
SOURCE: Hsu N et al. CHEST. 2018 Oct. doi: 10.1016/j.chest.2018.08.937
SAN ANTONIO – The recommended approach to evaluating suspected pulmonary embolism is “greatly underutilized” in the Veterans Health Administration system, Nancy Hsu, MD, said at the annual meeting of the American College of Chest Physicians.
Most Veterans Affairs sites did not require incorporation of a clinical decision rule (CDR) and highly sensitive D-dimer prior to ordering CT pulmonary angiography (CTPA) for suspected pulmonary embolism (PE), according to results of a survey by Dr. Hsu and her coinvestigator, Guy Soo Hoo, MD.
While CTPA has become the imaging modality of choice for evaluating suspected PE, it is overused and potentially avoidable in one-third of cases, said Dr. Hsu, who is with the VA Greater Los Angeles Healthcare System.
“In the 10 years following the advent of CTPA use, there was a 14-fold increase in usage, but there was no change in mortality,” Dr. Hsu said. “This is consistent with overdiagnosis.”
Dr. Hsu said.
Dr. Hsu and Dr. Soo Hoo surveyed 606 individuals at 18 Veterans Integrated Service Networks (VISNs) and 143 medical centers. A total of 120 fully completed questionnaires were analyzed.
Most respondents (63%) were chiefs, and 80% had 11+ years of experience, Dr. Hsu reported.
Almost all respondents (85%) said CDR with or without D-dimer was not required before ordering a CTPA, survey results show, while only about 7% required both.
“A very small minority of [Veterans Integrated Service Networks], or geographic regions, contained even one hospital that adhered to the guidelines,” Dr. Hsu added.
Though further analysis was limited by sample size, the average CTPA yield for PE appeared to be higher when both components were used in the evaluation, according to Dr. Hsu, who noted an 11.9% yield for CDR plus D-dimer.
Use of CTPA appeared lower at sites with CDR and D-dimer testing, Dr. Hsu added.
These results suggest a need for further research to compare CTPA use and yield in sites that have the algorithm in place, Dr. Hsu told attendees at the meeting.
Adherence to the CDR plus D-dimer diagnostic strategy is “modest at best” despite being a Top 5 Choosing Wisely recommendation in pulmonary medicine, Dr. Hsu told attendees.
The biggest barrier to optimal practice may be the fear of having a patient who “falls through the cracks” based on false-negative CDR and D-dimer data, according to Dr. Hsu.
On the other hand, judicious use of CTPA likely avoids negative sequelae related to radiation, contrast exposure, and treatment-related bleeding, Dr. Hsu said.
“It’s all about balancing risks and benefits,” she said from the podium in a discussion of the study results.
Dr. Hsu and Dr. Soo Hoo disclosed that they had no relationships relevant to their research.
SOURCE: Hsu N et al. CHEST. 2018 Oct. doi: 10.1016/j.chest.2018.08.937
REPORTING FROM CHEST 2018
Key clinical point: The recommended approach to evaluating suspected pulmonary embolism was underutilized in VA facilities.
Major finding: 85% of respondents said incorporation of a clinical decision rule plus highly sensitive D-dimer was not required prior to CTPA.
Study details: Analysis of 120 survey questionnaires completed by individuals working in Veterans Integrated Service Networks and medical centers.
Disclosures: Study authors reported no conflicts of interest.
Source: Hsu N et al. CHEST 2018 Oct. doi: 10/1016/j.chest.2018.08.937.
Treating cryptococcal meningitis in patients with HIV
One-week treatment with amphotericin B deoxycholate (AmBd)– and flucytosine (5FC)–based therapy, followed by fluconazole (FLU) on days 8 through 14, is probably superior to other regimens for treatment of HIV-associated cryptococcal meningitis, according to the authors of a review of the available literature in the Cochrane Database of Systemic Reviews.
The review is an update of one previous previously published in 2011. The authors found 13 eligible studies that enrolled 2,426 participants and compared 21 interventions. They performed a network meta-analysis using multivariate meta-regression, modeled treatment differences (RR and 95% confidence interval), and determined treatment rankings for 2-week and 10-week mortality outcomes using surface under the cumulative ranking curve, which represents the probability that a treatment will present the best outcome with no uncertainty and was used to develop a hierarchy of treatments for HIV-associated cryptococcal meningitis.
In addition, certainty of the evidence was assessed using the GRADE approach, according to Mark W. Tenforde, MD, of the University of Washington School of Public Health, Seattle, and his colleagues.
They found “reduced 10-week mortality with shortened [AmBd and 5FC] induction therapy, compared to the current gold standard of 2 weeks of AmBd and 5FC, based on moderate-certainty evidence.” They also found no mortality benefit of combination 2 weeks AmBd and FLU, compared with AmBd alone.
“In resource-limited settings, 1-week AmBd- and 5FC-based therapy is probably superior to other regimens for treatment of HIV-associated cryptococcal meningitis,” they wrote. “An all-oral regimen of 2 weeks 5FC and FLU may be an alternative in settings where AmBd is unavailable or intravenous therapy cannot be safely administered.” These results indicated the need to expand access to 5FC in resource-limited settings in which HIV-associated cryptococcal meningitis is most common.
They also reported finding no mortality benefit of 2 weeks of combination AmBd and FLU, compared with AmBd alone.
“Given the absence of data from studies in children, and limited data from high-income countries, our findings provide limited guidance for treatment in these patients and settings,” Dr. Tenforde and his colleagues stated.
The authors reported that they had no relevant conflicts of interest.
SOURCE: Tenforde MW et al. Treatment for HIV-associated cryptococcal meningitis. Cochrane Database Syst Rev. 2018 Jul 25;7:CD005647. doi: 10.1002/14651858.CD005647.
One-week treatment with amphotericin B deoxycholate (AmBd)– and flucytosine (5FC)–based therapy, followed by fluconazole (FLU) on days 8 through 14, is probably superior to other regimens for treatment of HIV-associated cryptococcal meningitis, according to the authors of a review of the available literature in the Cochrane Database of Systemic Reviews.
The review is an update of one previous previously published in 2011. The authors found 13 eligible studies that enrolled 2,426 participants and compared 21 interventions. They performed a network meta-analysis using multivariate meta-regression, modeled treatment differences (RR and 95% confidence interval), and determined treatment rankings for 2-week and 10-week mortality outcomes using surface under the cumulative ranking curve, which represents the probability that a treatment will present the best outcome with no uncertainty and was used to develop a hierarchy of treatments for HIV-associated cryptococcal meningitis.
In addition, certainty of the evidence was assessed using the GRADE approach, according to Mark W. Tenforde, MD, of the University of Washington School of Public Health, Seattle, and his colleagues.
They found “reduced 10-week mortality with shortened [AmBd and 5FC] induction therapy, compared to the current gold standard of 2 weeks of AmBd and 5FC, based on moderate-certainty evidence.” They also found no mortality benefit of combination 2 weeks AmBd and FLU, compared with AmBd alone.
“In resource-limited settings, 1-week AmBd- and 5FC-based therapy is probably superior to other regimens for treatment of HIV-associated cryptococcal meningitis,” they wrote. “An all-oral regimen of 2 weeks 5FC and FLU may be an alternative in settings where AmBd is unavailable or intravenous therapy cannot be safely administered.” These results indicated the need to expand access to 5FC in resource-limited settings in which HIV-associated cryptococcal meningitis is most common.
They also reported finding no mortality benefit of 2 weeks of combination AmBd and FLU, compared with AmBd alone.
“Given the absence of data from studies in children, and limited data from high-income countries, our findings provide limited guidance for treatment in these patients and settings,” Dr. Tenforde and his colleagues stated.
The authors reported that they had no relevant conflicts of interest.
SOURCE: Tenforde MW et al. Treatment for HIV-associated cryptococcal meningitis. Cochrane Database Syst Rev. 2018 Jul 25;7:CD005647. doi: 10.1002/14651858.CD005647.
One-week treatment with amphotericin B deoxycholate (AmBd)– and flucytosine (5FC)–based therapy, followed by fluconazole (FLU) on days 8 through 14, is probably superior to other regimens for treatment of HIV-associated cryptococcal meningitis, according to the authors of a review of the available literature in the Cochrane Database of Systemic Reviews.
The review is an update of one previous previously published in 2011. The authors found 13 eligible studies that enrolled 2,426 participants and compared 21 interventions. They performed a network meta-analysis using multivariate meta-regression, modeled treatment differences (RR and 95% confidence interval), and determined treatment rankings for 2-week and 10-week mortality outcomes using surface under the cumulative ranking curve, which represents the probability that a treatment will present the best outcome with no uncertainty and was used to develop a hierarchy of treatments for HIV-associated cryptococcal meningitis.
In addition, certainty of the evidence was assessed using the GRADE approach, according to Mark W. Tenforde, MD, of the University of Washington School of Public Health, Seattle, and his colleagues.
They found “reduced 10-week mortality with shortened [AmBd and 5FC] induction therapy, compared to the current gold standard of 2 weeks of AmBd and 5FC, based on moderate-certainty evidence.” They also found no mortality benefit of combination 2 weeks AmBd and FLU, compared with AmBd alone.
“In resource-limited settings, 1-week AmBd- and 5FC-based therapy is probably superior to other regimens for treatment of HIV-associated cryptococcal meningitis,” they wrote. “An all-oral regimen of 2 weeks 5FC and FLU may be an alternative in settings where AmBd is unavailable or intravenous therapy cannot be safely administered.” These results indicated the need to expand access to 5FC in resource-limited settings in which HIV-associated cryptococcal meningitis is most common.
They also reported finding no mortality benefit of 2 weeks of combination AmBd and FLU, compared with AmBd alone.
“Given the absence of data from studies in children, and limited data from high-income countries, our findings provide limited guidance for treatment in these patients and settings,” Dr. Tenforde and his colleagues stated.
The authors reported that they had no relevant conflicts of interest.
SOURCE: Tenforde MW et al. Treatment for HIV-associated cryptococcal meningitis. Cochrane Database Syst Rev. 2018 Jul 25;7:CD005647. doi: 10.1002/14651858.CD005647.
FROM COCHRANE DATABASE OF SYSTEMIC REVIEWS
Key clinical point: Shorter drug treatment beat the gold standard for HIV-associated cryptococcal meningitis according to a literature review.
Major finding:
Study details: Updated review of articles, registries, and clinical trials during Jan. 1, 1980–July 9, 2018.
Disclosures: The authors reported that they had no relevant conflicts of interest.
Source: Tenforde MW et al. Treatment for HIV-associated cryptococcal meningitis. Cochrane Database Syst Rev. 2018 Jul 25;7:CD005647. doi: 10.1002/14651858.CD005647.
Relapsing-remitting MS best treated within 6 months of onset
BERLIN – according to real-world data from the Big Multiple Sclerosis Data Network.
Receiving disease-modifying treatments (DMTs) within 6 months of diagnosis was associated with a 28% reduction in the risk of reaching an Expanded Disability Status Scale score of 3.0 or more for the first time at 12 months versus receiving treatment after 6 months (hazard ratio, 0.72; 95% confidence interval, 0.59-0.90; P = .003).
Results were not significant, looking at all the other periods tested at 6-month intervals from 1 year up to 5 years after diagnosis. HRs (95% CIs) comparing a first DMT given at 1 year, 1.5 years, 2 years, 2.5 years, 3 years, 3.5 years, 4 years, 4.5 years, and 5 years were a respective 0.90 (0.78-1.03), 0.89 (0.79-1.01), 0.99 (0.88-1.11), 0.95 (0.85-1.06), 1.01 (0.90-1.12), 0.97 (0.86-1.09), 1.09 (0.96-1.22), 1.11 (0.98-1.25), and 1.06 (0.93-1.20).
“To date, these data represent the largest RRMS cohort with the longest follow-up ever analyzed to determine the long-term effectiveness of the early start of DMTs,” said Pietro Iaffaldano, MD, at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.
“This study also provides evidence that data sharing from MS registries and databases is feasible,” noted Dr. Iaffaldano, who is assistant professor of neurology at the University of Bari (Italy). Such an approach can provide enough statistical power to detect the impact of treatment on disability outcomes in the long term, he suggested.
For the study, a cohort of 11,934 patients was obtained by screening more than 149,636 patients from five large registries and databases of MS patients – the Italian MS Registry, the Swedish MS Registry, the Danish MS Registry, OFSEP (Observatoire Français de al Sclérose en Plaques), and MSBase. Patients were included in the current analysis if they had at least 10 years of follow-up, had at least three EDSS evaluations, and at least one DMT prescription.
“It is well known that randomized, controlled trials support the early start of treatment in MS, but open-label extensions of the same trials reported inconsistent results about the long-term benefit on disability accumulation,” Dr. Iaffaldano explained. Further, recent observational studies have suggested that initiating DMTs early might not only delay the accumulation of disability but perhaps also death.
The aim of the research was thus to look at what effect the time interval from disease onset to the first administration of a DMT might have on long-term disability accumulation, as measured by the EDSS, in patients with RRMS.
The population of patients studied was mostly (71%) female, with a median age of 27 years at disease onset. The number of relapses prior to starting a DMT was two and the baseline EDSS was 2.0. In almost all (98.9%) cases, DMT was used as first-line treatment (second line in 1.1% of cases). The median follow-up was 13.2 years and cumulative DMT exposure was 10.5 years.
The work was supported by Biogen International on the basis of a sponsored research agreement with the Big Multiple Sclerosis Data Network. Dr. Iaffaldano has served on scientific advisory boards for and received funding for travel and/or speaker honoraria from Biogen and other companies that market DMTs for MS. Several study authors are employees of Biogen, and other study authors also reported financial ties to Biogen and other pharmaceutical companies.
SOURCE: Iaffaldano P et al. Mult Scler. 2018;24(Suppl 2):71-2, Abstract 204.
BERLIN – according to real-world data from the Big Multiple Sclerosis Data Network.
Receiving disease-modifying treatments (DMTs) within 6 months of diagnosis was associated with a 28% reduction in the risk of reaching an Expanded Disability Status Scale score of 3.0 or more for the first time at 12 months versus receiving treatment after 6 months (hazard ratio, 0.72; 95% confidence interval, 0.59-0.90; P = .003).
Results were not significant, looking at all the other periods tested at 6-month intervals from 1 year up to 5 years after diagnosis. HRs (95% CIs) comparing a first DMT given at 1 year, 1.5 years, 2 years, 2.5 years, 3 years, 3.5 years, 4 years, 4.5 years, and 5 years were a respective 0.90 (0.78-1.03), 0.89 (0.79-1.01), 0.99 (0.88-1.11), 0.95 (0.85-1.06), 1.01 (0.90-1.12), 0.97 (0.86-1.09), 1.09 (0.96-1.22), 1.11 (0.98-1.25), and 1.06 (0.93-1.20).
“To date, these data represent the largest RRMS cohort with the longest follow-up ever analyzed to determine the long-term effectiveness of the early start of DMTs,” said Pietro Iaffaldano, MD, at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.
“This study also provides evidence that data sharing from MS registries and databases is feasible,” noted Dr. Iaffaldano, who is assistant professor of neurology at the University of Bari (Italy). Such an approach can provide enough statistical power to detect the impact of treatment on disability outcomes in the long term, he suggested.
For the study, a cohort of 11,934 patients was obtained by screening more than 149,636 patients from five large registries and databases of MS patients – the Italian MS Registry, the Swedish MS Registry, the Danish MS Registry, OFSEP (Observatoire Français de al Sclérose en Plaques), and MSBase. Patients were included in the current analysis if they had at least 10 years of follow-up, had at least three EDSS evaluations, and at least one DMT prescription.
“It is well known that randomized, controlled trials support the early start of treatment in MS, but open-label extensions of the same trials reported inconsistent results about the long-term benefit on disability accumulation,” Dr. Iaffaldano explained. Further, recent observational studies have suggested that initiating DMTs early might not only delay the accumulation of disability but perhaps also death.
The aim of the research was thus to look at what effect the time interval from disease onset to the first administration of a DMT might have on long-term disability accumulation, as measured by the EDSS, in patients with RRMS.
The population of patients studied was mostly (71%) female, with a median age of 27 years at disease onset. The number of relapses prior to starting a DMT was two and the baseline EDSS was 2.0. In almost all (98.9%) cases, DMT was used as first-line treatment (second line in 1.1% of cases). The median follow-up was 13.2 years and cumulative DMT exposure was 10.5 years.
The work was supported by Biogen International on the basis of a sponsored research agreement with the Big Multiple Sclerosis Data Network. Dr. Iaffaldano has served on scientific advisory boards for and received funding for travel and/or speaker honoraria from Biogen and other companies that market DMTs for MS. Several study authors are employees of Biogen, and other study authors also reported financial ties to Biogen and other pharmaceutical companies.
SOURCE: Iaffaldano P et al. Mult Scler. 2018;24(Suppl 2):71-2, Abstract 204.
BERLIN – according to real-world data from the Big Multiple Sclerosis Data Network.
Receiving disease-modifying treatments (DMTs) within 6 months of diagnosis was associated with a 28% reduction in the risk of reaching an Expanded Disability Status Scale score of 3.0 or more for the first time at 12 months versus receiving treatment after 6 months (hazard ratio, 0.72; 95% confidence interval, 0.59-0.90; P = .003).
Results were not significant, looking at all the other periods tested at 6-month intervals from 1 year up to 5 years after diagnosis. HRs (95% CIs) comparing a first DMT given at 1 year, 1.5 years, 2 years, 2.5 years, 3 years, 3.5 years, 4 years, 4.5 years, and 5 years were a respective 0.90 (0.78-1.03), 0.89 (0.79-1.01), 0.99 (0.88-1.11), 0.95 (0.85-1.06), 1.01 (0.90-1.12), 0.97 (0.86-1.09), 1.09 (0.96-1.22), 1.11 (0.98-1.25), and 1.06 (0.93-1.20).
“To date, these data represent the largest RRMS cohort with the longest follow-up ever analyzed to determine the long-term effectiveness of the early start of DMTs,” said Pietro Iaffaldano, MD, at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.
“This study also provides evidence that data sharing from MS registries and databases is feasible,” noted Dr. Iaffaldano, who is assistant professor of neurology at the University of Bari (Italy). Such an approach can provide enough statistical power to detect the impact of treatment on disability outcomes in the long term, he suggested.
For the study, a cohort of 11,934 patients was obtained by screening more than 149,636 patients from five large registries and databases of MS patients – the Italian MS Registry, the Swedish MS Registry, the Danish MS Registry, OFSEP (Observatoire Français de al Sclérose en Plaques), and MSBase. Patients were included in the current analysis if they had at least 10 years of follow-up, had at least three EDSS evaluations, and at least one DMT prescription.
“It is well known that randomized, controlled trials support the early start of treatment in MS, but open-label extensions of the same trials reported inconsistent results about the long-term benefit on disability accumulation,” Dr. Iaffaldano explained. Further, recent observational studies have suggested that initiating DMTs early might not only delay the accumulation of disability but perhaps also death.
The aim of the research was thus to look at what effect the time interval from disease onset to the first administration of a DMT might have on long-term disability accumulation, as measured by the EDSS, in patients with RRMS.
The population of patients studied was mostly (71%) female, with a median age of 27 years at disease onset. The number of relapses prior to starting a DMT was two and the baseline EDSS was 2.0. In almost all (98.9%) cases, DMT was used as first-line treatment (second line in 1.1% of cases). The median follow-up was 13.2 years and cumulative DMT exposure was 10.5 years.
The work was supported by Biogen International on the basis of a sponsored research agreement with the Big Multiple Sclerosis Data Network. Dr. Iaffaldano has served on scientific advisory boards for and received funding for travel and/or speaker honoraria from Biogen and other companies that market DMTs for MS. Several study authors are employees of Biogen, and other study authors also reported financial ties to Biogen and other pharmaceutical companies.
SOURCE: Iaffaldano P et al. Mult Scler. 2018;24(Suppl 2):71-2, Abstract 204.
REPORTING FROM ECTRIMS 2018
Key clinical point: Less disease progression occurs if disease-modifying treatments (DMTs) are given early in relapsing-remitting multiple sclerosis (RRMS).
Major finding: DMTs within 6 months vs. later decreased the risk of confirmed first disability progression at 12 months by 28% (P = .003).
Study details: 11,934 patients with RRMS with at least 10 years’ follow-up, three or more Expanded Disability Status Scale evaluations, and at least one DMT prescription.
Disclosures: The work was supported by Biogen International on the basis of a sponsored research agreement with the Big Multiple Sclerosis Data Network. Dr. Iaffaldano has served on scientific advisory boards for and received funding for travel and/or speaker honoraria from Biogen and other companies that market DMTs for MS. Several study authors are employees of Biogen, and other study authors also reported financial ties to Biogen and other pharmaceutical companies.
Source: Iaffaldano P et al. Mult Scler. 2018;24(Suppl 2):71-2, Abstract 204.
Sex workers: High rates of HIV, low rates of treatment
The HIV pandemic among sex workers remains underaddressed and underresourced, with “glaring gaps” in comprehensive measures of HIV prevalence and incidence, and in prevention and treatment, according to the results of an updated literature review published in the Lancet.
Kate Shannon, PhD, director of the gender and sexual health initiative at the University of British Columbia, Vancouver, and her colleagues updated a 2013 literature search for the Lancet series on HIV and sex workers to include reports and manuscripts published from Jan. 1, 2006, to Sept. 6, 2017.
They found that In particular, 4 years after their previous Lancet series on HIV and sex workers, this updated analysis showed that the global HIV burden among female sex workers was still similar to the previously determined 11.8% and “unacceptably high” at 10.4%, (95% confidence interval, 9.5-11.5).
Although there has been some improvement in the assessment of HIV in transgender women since the previous analysis, according to Dr. Shannon and her colleagues, small sample sizes and conflation of transgender women and men who have sex with men (MSM) continue to limit the volume of transgender-specific HIV data, particularly in Africa.
Access to HIV prevention and treatment also remains a considerable problem for sex workers, according to the authors. In particular, “qualitative data in sub-Saharan Africa suggest that profound structural barriers of stigma and discrimination impede progress in the HIV care continuum,” with studies confirming that “successful HIV treatment trajectories are impeded by violence and displacement” because of policing, they wrote.
They pointed out that things may well become worse, with evidence-based progress on full decriminalization grounded in health and human rights – which was a key recommendation in their earlier Lancet Series – having stalled in all but South Africa. In fact, they reported that several countries had even rolled back rights further for sex workers.
“HIV prevention and treatment tools are available but, without comprehensive HIV epidemiology, a lack of denominators and failure to address structural determinants (including decriminalisation of sex work) means that progress in achieving health and rights for all sex workers will fall short,” the researchers concluded.
The authors reported that they had no competing interests.
SOURCE: Shannon K et al. Lancet. 2018 Aug 25;392:698-710.
The HIV pandemic among sex workers remains underaddressed and underresourced, with “glaring gaps” in comprehensive measures of HIV prevalence and incidence, and in prevention and treatment, according to the results of an updated literature review published in the Lancet.
Kate Shannon, PhD, director of the gender and sexual health initiative at the University of British Columbia, Vancouver, and her colleagues updated a 2013 literature search for the Lancet series on HIV and sex workers to include reports and manuscripts published from Jan. 1, 2006, to Sept. 6, 2017.
They found that In particular, 4 years after their previous Lancet series on HIV and sex workers, this updated analysis showed that the global HIV burden among female sex workers was still similar to the previously determined 11.8% and “unacceptably high” at 10.4%, (95% confidence interval, 9.5-11.5).
Although there has been some improvement in the assessment of HIV in transgender women since the previous analysis, according to Dr. Shannon and her colleagues, small sample sizes and conflation of transgender women and men who have sex with men (MSM) continue to limit the volume of transgender-specific HIV data, particularly in Africa.
Access to HIV prevention and treatment also remains a considerable problem for sex workers, according to the authors. In particular, “qualitative data in sub-Saharan Africa suggest that profound structural barriers of stigma and discrimination impede progress in the HIV care continuum,” with studies confirming that “successful HIV treatment trajectories are impeded by violence and displacement” because of policing, they wrote.
They pointed out that things may well become worse, with evidence-based progress on full decriminalization grounded in health and human rights – which was a key recommendation in their earlier Lancet Series – having stalled in all but South Africa. In fact, they reported that several countries had even rolled back rights further for sex workers.
“HIV prevention and treatment tools are available but, without comprehensive HIV epidemiology, a lack of denominators and failure to address structural determinants (including decriminalisation of sex work) means that progress in achieving health and rights for all sex workers will fall short,” the researchers concluded.
The authors reported that they had no competing interests.
SOURCE: Shannon K et al. Lancet. 2018 Aug 25;392:698-710.
The HIV pandemic among sex workers remains underaddressed and underresourced, with “glaring gaps” in comprehensive measures of HIV prevalence and incidence, and in prevention and treatment, according to the results of an updated literature review published in the Lancet.
Kate Shannon, PhD, director of the gender and sexual health initiative at the University of British Columbia, Vancouver, and her colleagues updated a 2013 literature search for the Lancet series on HIV and sex workers to include reports and manuscripts published from Jan. 1, 2006, to Sept. 6, 2017.
They found that In particular, 4 years after their previous Lancet series on HIV and sex workers, this updated analysis showed that the global HIV burden among female sex workers was still similar to the previously determined 11.8% and “unacceptably high” at 10.4%, (95% confidence interval, 9.5-11.5).
Although there has been some improvement in the assessment of HIV in transgender women since the previous analysis, according to Dr. Shannon and her colleagues, small sample sizes and conflation of transgender women and men who have sex with men (MSM) continue to limit the volume of transgender-specific HIV data, particularly in Africa.
Access to HIV prevention and treatment also remains a considerable problem for sex workers, according to the authors. In particular, “qualitative data in sub-Saharan Africa suggest that profound structural barriers of stigma and discrimination impede progress in the HIV care continuum,” with studies confirming that “successful HIV treatment trajectories are impeded by violence and displacement” because of policing, they wrote.
They pointed out that things may well become worse, with evidence-based progress on full decriminalization grounded in health and human rights – which was a key recommendation in their earlier Lancet Series – having stalled in all but South Africa. In fact, they reported that several countries had even rolled back rights further for sex workers.
“HIV prevention and treatment tools are available but, without comprehensive HIV epidemiology, a lack of denominators and failure to address structural determinants (including decriminalisation of sex work) means that progress in achieving health and rights for all sex workers will fall short,” the researchers concluded.
The authors reported that they had no competing interests.
SOURCE: Shannon K et al. Lancet. 2018 Aug 25;392:698-710.
FROM THE LANCET
Key clinical point: The HIV pandemic among sex workers remains underaddressed and underresourced, with “glaring gaps” in assessment, treatment.
Major finding: The global HIV burden among female sex workers shows that HIV prevalence was “unacceptably high” at 10.4%.
Study details: Researchers updated a 2013 literature review with reports published from Jan. 1, 2006, to Sept. 6, 2017.
Disclosures: The authors reported that they had no competing interests.
Source: Shannon K et al. Lancet. 2018 Aug 25;392:698-710.
First Episode: Dr. Lorenzo Norris
At MDedge, we know that medicine can be a bit of an awakening at every step of your career. So, we launched the Postcall Podcast as a way to share your stories: what you love about medicine and what you love outside of your career. This podcast is meant to be a place for you to find your truth.
In the first edition, MDedge producer and host Nick Andrews sits down with Lorenzo Norris, MD. Dr. Norris is the host of the MDedge Psychcast as well as the editor-in-chief of MDedge Psychiatry and Dean at the George Washington University School of Medicine and Health Sciences.
Subscribe to the Postcall Podcast:
Apple Podcasts
Google Podcasts
At MDedge, we know that medicine can be a bit of an awakening at every step of your career. So, we launched the Postcall Podcast as a way to share your stories: what you love about medicine and what you love outside of your career. This podcast is meant to be a place for you to find your truth.
In the first edition, MDedge producer and host Nick Andrews sits down with Lorenzo Norris, MD. Dr. Norris is the host of the MDedge Psychcast as well as the editor-in-chief of MDedge Psychiatry and Dean at the George Washington University School of Medicine and Health Sciences.
Subscribe to the Postcall Podcast:
Apple Podcasts
Google Podcasts
At MDedge, we know that medicine can be a bit of an awakening at every step of your career. So, we launched the Postcall Podcast as a way to share your stories: what you love about medicine and what you love outside of your career. This podcast is meant to be a place for you to find your truth.
In the first edition, MDedge producer and host Nick Andrews sits down with Lorenzo Norris, MD. Dr. Norris is the host of the MDedge Psychcast as well as the editor-in-chief of MDedge Psychiatry and Dean at the George Washington University School of Medicine and Health Sciences.
Subscribe to the Postcall Podcast:
Apple Podcasts
Google Podcasts
The challenges of diagnosing CMML
DUBROVNIK, CROATIA—Diagnosing chronic myelomonocytic leukemia (CMML) remains a challenge in 2018, according to a presentation at Leukemia and Lymphoma: Europe and the USA, Linking Knowledge and Practice.
Even with updated World Health Organization (WHO) criteria, karyotyping, and genetic analyses, it can be difficult to distinguish CMML from other conditions, according to Nadira Duraković, MD, PhD, of the University Hospital Zagreb in Croatia.
However, Dr. Duraković said there are characteristics that differentiate CMML from myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPNs), and atypical chronic myeloid leukemia (CML).
Furthermore, studies have suggested that monocyte subset distribution analysis can be useful for diagnosing CMML.
Dr. Duraković began her presentation with an overview of the 2016 WHO classification of CMML (Blood 2016 127:2391-2405).
According to the WHO, patients have CMML if:
- They have persistent peripheral blood monocytosis (1×109/L) with monocytes accounting for 10% of the white blood cell count
- They do not meet WHO criteria for BCR-ABL1-positive CML, primary myelofibrosis, polycythemia vera, or essential thrombocythemia
- There is no evidence of PCM1-JAK2 or PDGFRA, PDGFRB, or FGFR1 rearrangement
- They have fewer than 20% blasts in the blood and bone marrow
- They have dysplasia in one or more myeloid lineages
- If myelodysplasia is absent or minimal, an acquired clonal cytogenetic or molecular genetic abnormality must be present.
Alternatively, if patients have monocytosis that has persisted for at least 3 months, and all other causes of monocytosis have been excluded, “you can say that your patient has CMML,” Dr. Duraković said.
Other causes of monocytosis include infections, malignancies, medications, inflammatory conditions, and other conditions such as pregnancy.
However, Dr. Duraković pointed out that the cause of monocytosis cannot always be determined, and, in some cases, CMML patients may not meet the WHO criteria.
“[T]here are cases where there just aren’t enough monocytes to fulfill the WHO criteria,” Dr. Duraković said. “You can have a patient with peripheral blood cytopenia and monocytosis who does not have 1,000 monocytes. Patients can have progressive dysplasia, can have splenomegaly, be really sick, but fail to meet WHO criteria.”
Distinguishing CMML from other conditions
“Differentiating CMML from myelodysplastic syndromes can be tough,” Dr. Duraković said. “There are dysplastic features that are present in CMML . . . but, in CMML, they are more subtle, and they are more difficult to appreciate than in myelodysplastic syndromes.”
The ratio of myeloid to erythroid cells is elevated in CMML, and patients may have atypical monocytes (paramyeloid cells) that are unique to CMML.
Dr. Duraković noted that megakaryocyte dysplasia in CMML can be characterized by “myeloproliferative megakaryocytes,” which are large cells that cluster and have hyperlobulated nuclei, or “MDS megakaryocytes,” which are small, solitary cells with hypolobulated nuclei.
She went on to explain that “MPN phenotype” CMML is characterized by leukocytosis, monocytosis, hepatomegaly, splenomegaly, and clinical features of myeloproliferation (fatigue, night sweats, bone pain, weight loss, etc.).
Thirty percent of cases are associated with splenomegaly, and 30% of patients can have an increase in bone marrow reticulin fibrosis.
Dr. Duraković also noted that a prior MPN diagnosis excludes CMML. The presence of common MPN mutations, such as JAK2, CALR, or MPL, suggests a patient has an MPN with monocytosis rather than CMML.
Patients who have unclassified MPNs or MDS, rather than CMML, either do not have 1,000 monocytes or the monocytes do not represent more than 10% of the differential, Dr. Duraković said.
She also noted that it can be difficult to differentiate CMML from atypical CML.
“Atypical CML is characterized by profound dysgranulopoiesis, absence of the BCR-ABL1 fusion gene, and neutrophilia,” Dr. Duraković explained. “Those patients [commonly] have monocytosis, but, here, that 10% rule is valuable because their monocytes comprise less than 10% of the entire white blood cell count.”
Karyotyping, genotyping, and immunophenotyping
“There is no disease-defining karyotype abnormality [in CMML],” Dr. Duraković noted.
She said 30% of patients have abnormal karyotype, and the most common abnormality is trisomy 8. Unlike in patients with MDS, del(5q) and monosomal karyotypes are infrequent in patients with CMML.
Similarly, there are no “disease-defining” mutations or genetic changes in CMML, although CMML is genetically distinct from MDS, Dr. Duraković said.
For instance, SRSF2 encodes a component of the spliceosome that is mutated in almost half of CMML patients and less than 10% of MDS patients. Likewise, ASLX1 and TET2 are “much more frequently involved” in CMML than in MDS, Dr. Duraković said.
In a 2012 study of 275 CMML patients, researchers found that 93% of patients had at least one somatic mutation in nine recurrently mutated genes—SRFS2, ASXL1, CBL, EZH2, JAK2V617F, KRAS, NRAS, RUNX1, and TET2 (Blood 2012 120:3080-3088).
However, Dr. Duraković noted that these mutations are found in other disorders as well, so this information may not be helpful in differentiating CMML from other disorders.
A 2015 study revealed a technique that does appear useful for identifying CMML—monocyte subset distribution analysis (Blood 2015 125(23): 3618–3626).
For this analysis, monocytes are divided into the following categories:
- Classical/MO1 (CD14bright/CD16−)
- Intermediate/MO2 (CD14bright/CD16+)
- Non-classical/MO3 (CD14dim/CD16+).
The researchers found that CMML patients had an increase in the fraction of classical monocytes (with a cutoff value of 94.0%), as compared to healthy control subjects, patients with another hematologic disorder, and patients with reactive monocytosis.
A 2018 study confirmed that monocyte subset distribution analysis could differentiate CMML from other hematologic disorders, with the exception of atypical CML (Am J Clin Pathol 2018 150(4):293-302).
This study also suggested that a decreased percentage of non-classical monocytes was more sensitive than an increased percentage of classical monocytes.
Despite the differences between these studies, “monocyte subset distribution analysis is showing promise as a method of identifying hard-to-identify CMML patients with ease and affordability,” Dr. Duraković said.
She added that the technique can be implemented in clinical practice using the HematoflowTM solution (Cytometry B Clin Cytom 2018 94(5):658-661).
Dr. Duraković did not report any conflicts of interest.
DUBROVNIK, CROATIA—Diagnosing chronic myelomonocytic leukemia (CMML) remains a challenge in 2018, according to a presentation at Leukemia and Lymphoma: Europe and the USA, Linking Knowledge and Practice.
Even with updated World Health Organization (WHO) criteria, karyotyping, and genetic analyses, it can be difficult to distinguish CMML from other conditions, according to Nadira Duraković, MD, PhD, of the University Hospital Zagreb in Croatia.
However, Dr. Duraković said there are characteristics that differentiate CMML from myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPNs), and atypical chronic myeloid leukemia (CML).
Furthermore, studies have suggested that monocyte subset distribution analysis can be useful for diagnosing CMML.
Dr. Duraković began her presentation with an overview of the 2016 WHO classification of CMML (Blood 2016 127:2391-2405).
According to the WHO, patients have CMML if:
- They have persistent peripheral blood monocytosis (1×109/L) with monocytes accounting for 10% of the white blood cell count
- They do not meet WHO criteria for BCR-ABL1-positive CML, primary myelofibrosis, polycythemia vera, or essential thrombocythemia
- There is no evidence of PCM1-JAK2 or PDGFRA, PDGFRB, or FGFR1 rearrangement
- They have fewer than 20% blasts in the blood and bone marrow
- They have dysplasia in one or more myeloid lineages
- If myelodysplasia is absent or minimal, an acquired clonal cytogenetic or molecular genetic abnormality must be present.
Alternatively, if patients have monocytosis that has persisted for at least 3 months, and all other causes of monocytosis have been excluded, “you can say that your patient has CMML,” Dr. Duraković said.
Other causes of monocytosis include infections, malignancies, medications, inflammatory conditions, and other conditions such as pregnancy.
However, Dr. Duraković pointed out that the cause of monocytosis cannot always be determined, and, in some cases, CMML patients may not meet the WHO criteria.
“[T]here are cases where there just aren’t enough monocytes to fulfill the WHO criteria,” Dr. Duraković said. “You can have a patient with peripheral blood cytopenia and monocytosis who does not have 1,000 monocytes. Patients can have progressive dysplasia, can have splenomegaly, be really sick, but fail to meet WHO criteria.”
Distinguishing CMML from other conditions
“Differentiating CMML from myelodysplastic syndromes can be tough,” Dr. Duraković said. “There are dysplastic features that are present in CMML . . . but, in CMML, they are more subtle, and they are more difficult to appreciate than in myelodysplastic syndromes.”
The ratio of myeloid to erythroid cells is elevated in CMML, and patients may have atypical monocytes (paramyeloid cells) that are unique to CMML.
Dr. Duraković noted that megakaryocyte dysplasia in CMML can be characterized by “myeloproliferative megakaryocytes,” which are large cells that cluster and have hyperlobulated nuclei, or “MDS megakaryocytes,” which are small, solitary cells with hypolobulated nuclei.
She went on to explain that “MPN phenotype” CMML is characterized by leukocytosis, monocytosis, hepatomegaly, splenomegaly, and clinical features of myeloproliferation (fatigue, night sweats, bone pain, weight loss, etc.).
Thirty percent of cases are associated with splenomegaly, and 30% of patients can have an increase in bone marrow reticulin fibrosis.
Dr. Duraković also noted that a prior MPN diagnosis excludes CMML. The presence of common MPN mutations, such as JAK2, CALR, or MPL, suggests a patient has an MPN with monocytosis rather than CMML.
Patients who have unclassified MPNs or MDS, rather than CMML, either do not have 1,000 monocytes or the monocytes do not represent more than 10% of the differential, Dr. Duraković said.
She also noted that it can be difficult to differentiate CMML from atypical CML.
“Atypical CML is characterized by profound dysgranulopoiesis, absence of the BCR-ABL1 fusion gene, and neutrophilia,” Dr. Duraković explained. “Those patients [commonly] have monocytosis, but, here, that 10% rule is valuable because their monocytes comprise less than 10% of the entire white blood cell count.”
Karyotyping, genotyping, and immunophenotyping
“There is no disease-defining karyotype abnormality [in CMML],” Dr. Duraković noted.
She said 30% of patients have abnormal karyotype, and the most common abnormality is trisomy 8. Unlike in patients with MDS, del(5q) and monosomal karyotypes are infrequent in patients with CMML.
Similarly, there are no “disease-defining” mutations or genetic changes in CMML, although CMML is genetically distinct from MDS, Dr. Duraković said.
For instance, SRSF2 encodes a component of the spliceosome that is mutated in almost half of CMML patients and less than 10% of MDS patients. Likewise, ASLX1 and TET2 are “much more frequently involved” in CMML than in MDS, Dr. Duraković said.
In a 2012 study of 275 CMML patients, researchers found that 93% of patients had at least one somatic mutation in nine recurrently mutated genes—SRFS2, ASXL1, CBL, EZH2, JAK2V617F, KRAS, NRAS, RUNX1, and TET2 (Blood 2012 120:3080-3088).
However, Dr. Duraković noted that these mutations are found in other disorders as well, so this information may not be helpful in differentiating CMML from other disorders.
A 2015 study revealed a technique that does appear useful for identifying CMML—monocyte subset distribution analysis (Blood 2015 125(23): 3618–3626).
For this analysis, monocytes are divided into the following categories:
- Classical/MO1 (CD14bright/CD16−)
- Intermediate/MO2 (CD14bright/CD16+)
- Non-classical/MO3 (CD14dim/CD16+).
The researchers found that CMML patients had an increase in the fraction of classical monocytes (with a cutoff value of 94.0%), as compared to healthy control subjects, patients with another hematologic disorder, and patients with reactive monocytosis.
A 2018 study confirmed that monocyte subset distribution analysis could differentiate CMML from other hematologic disorders, with the exception of atypical CML (Am J Clin Pathol 2018 150(4):293-302).
This study also suggested that a decreased percentage of non-classical monocytes was more sensitive than an increased percentage of classical monocytes.
Despite the differences between these studies, “monocyte subset distribution analysis is showing promise as a method of identifying hard-to-identify CMML patients with ease and affordability,” Dr. Duraković said.
She added that the technique can be implemented in clinical practice using the HematoflowTM solution (Cytometry B Clin Cytom 2018 94(5):658-661).
Dr. Duraković did not report any conflicts of interest.
DUBROVNIK, CROATIA—Diagnosing chronic myelomonocytic leukemia (CMML) remains a challenge in 2018, according to a presentation at Leukemia and Lymphoma: Europe and the USA, Linking Knowledge and Practice.
Even with updated World Health Organization (WHO) criteria, karyotyping, and genetic analyses, it can be difficult to distinguish CMML from other conditions, according to Nadira Duraković, MD, PhD, of the University Hospital Zagreb in Croatia.
However, Dr. Duraković said there are characteristics that differentiate CMML from myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPNs), and atypical chronic myeloid leukemia (CML).
Furthermore, studies have suggested that monocyte subset distribution analysis can be useful for diagnosing CMML.
Dr. Duraković began her presentation with an overview of the 2016 WHO classification of CMML (Blood 2016 127:2391-2405).
According to the WHO, patients have CMML if:
- They have persistent peripheral blood monocytosis (1×109/L) with monocytes accounting for 10% of the white blood cell count
- They do not meet WHO criteria for BCR-ABL1-positive CML, primary myelofibrosis, polycythemia vera, or essential thrombocythemia
- There is no evidence of PCM1-JAK2 or PDGFRA, PDGFRB, or FGFR1 rearrangement
- They have fewer than 20% blasts in the blood and bone marrow
- They have dysplasia in one or more myeloid lineages
- If myelodysplasia is absent or minimal, an acquired clonal cytogenetic or molecular genetic abnormality must be present.
Alternatively, if patients have monocytosis that has persisted for at least 3 months, and all other causes of monocytosis have been excluded, “you can say that your patient has CMML,” Dr. Duraković said.
Other causes of monocytosis include infections, malignancies, medications, inflammatory conditions, and other conditions such as pregnancy.
However, Dr. Duraković pointed out that the cause of monocytosis cannot always be determined, and, in some cases, CMML patients may not meet the WHO criteria.
“[T]here are cases where there just aren’t enough monocytes to fulfill the WHO criteria,” Dr. Duraković said. “You can have a patient with peripheral blood cytopenia and monocytosis who does not have 1,000 monocytes. Patients can have progressive dysplasia, can have splenomegaly, be really sick, but fail to meet WHO criteria.”
Distinguishing CMML from other conditions
“Differentiating CMML from myelodysplastic syndromes can be tough,” Dr. Duraković said. “There are dysplastic features that are present in CMML . . . but, in CMML, they are more subtle, and they are more difficult to appreciate than in myelodysplastic syndromes.”
The ratio of myeloid to erythroid cells is elevated in CMML, and patients may have atypical monocytes (paramyeloid cells) that are unique to CMML.
Dr. Duraković noted that megakaryocyte dysplasia in CMML can be characterized by “myeloproliferative megakaryocytes,” which are large cells that cluster and have hyperlobulated nuclei, or “MDS megakaryocytes,” which are small, solitary cells with hypolobulated nuclei.
She went on to explain that “MPN phenotype” CMML is characterized by leukocytosis, monocytosis, hepatomegaly, splenomegaly, and clinical features of myeloproliferation (fatigue, night sweats, bone pain, weight loss, etc.).
Thirty percent of cases are associated with splenomegaly, and 30% of patients can have an increase in bone marrow reticulin fibrosis.
Dr. Duraković also noted that a prior MPN diagnosis excludes CMML. The presence of common MPN mutations, such as JAK2, CALR, or MPL, suggests a patient has an MPN with monocytosis rather than CMML.
Patients who have unclassified MPNs or MDS, rather than CMML, either do not have 1,000 monocytes or the monocytes do not represent more than 10% of the differential, Dr. Duraković said.
She also noted that it can be difficult to differentiate CMML from atypical CML.
“Atypical CML is characterized by profound dysgranulopoiesis, absence of the BCR-ABL1 fusion gene, and neutrophilia,” Dr. Duraković explained. “Those patients [commonly] have monocytosis, but, here, that 10% rule is valuable because their monocytes comprise less than 10% of the entire white blood cell count.”
Karyotyping, genotyping, and immunophenotyping
“There is no disease-defining karyotype abnormality [in CMML],” Dr. Duraković noted.
She said 30% of patients have abnormal karyotype, and the most common abnormality is trisomy 8. Unlike in patients with MDS, del(5q) and monosomal karyotypes are infrequent in patients with CMML.
Similarly, there are no “disease-defining” mutations or genetic changes in CMML, although CMML is genetically distinct from MDS, Dr. Duraković said.
For instance, SRSF2 encodes a component of the spliceosome that is mutated in almost half of CMML patients and less than 10% of MDS patients. Likewise, ASLX1 and TET2 are “much more frequently involved” in CMML than in MDS, Dr. Duraković said.
In a 2012 study of 275 CMML patients, researchers found that 93% of patients had at least one somatic mutation in nine recurrently mutated genes—SRFS2, ASXL1, CBL, EZH2, JAK2V617F, KRAS, NRAS, RUNX1, and TET2 (Blood 2012 120:3080-3088).
However, Dr. Duraković noted that these mutations are found in other disorders as well, so this information may not be helpful in differentiating CMML from other disorders.
A 2015 study revealed a technique that does appear useful for identifying CMML—monocyte subset distribution analysis (Blood 2015 125(23): 3618–3626).
For this analysis, monocytes are divided into the following categories:
- Classical/MO1 (CD14bright/CD16−)
- Intermediate/MO2 (CD14bright/CD16+)
- Non-classical/MO3 (CD14dim/CD16+).
The researchers found that CMML patients had an increase in the fraction of classical monocytes (with a cutoff value of 94.0%), as compared to healthy control subjects, patients with another hematologic disorder, and patients with reactive monocytosis.
A 2018 study confirmed that monocyte subset distribution analysis could differentiate CMML from other hematologic disorders, with the exception of atypical CML (Am J Clin Pathol 2018 150(4):293-302).
This study also suggested that a decreased percentage of non-classical monocytes was more sensitive than an increased percentage of classical monocytes.
Despite the differences between these studies, “monocyte subset distribution analysis is showing promise as a method of identifying hard-to-identify CMML patients with ease and affordability,” Dr. Duraković said.
She added that the technique can be implemented in clinical practice using the HematoflowTM solution (Cytometry B Clin Cytom 2018 94(5):658-661).
Dr. Duraković did not report any conflicts of interest.
Crizanlizumab appears effective across subgroups
Crizanlizumab can reduce vaso-occlusive crises (VOCs) across subgroups of patients with sickle cell disease (SCD), according to a post-hoc analysis of the phase 2 SUSTAIN trial.
Researchers found crizanlizumab was more effective than placebo at delaying time to first VOC and eliminating crises in patients who had numerous previous crises, exhibited the HbSS genotype, or were taking concomitant hydroxyurea.
Abdullah Kutlar, MD, of the Medical College of Georgia in Augusta, and his colleagues reported these findings in the American Journal of Hematology.
The phase 2 SUSTAIN trial previously showed that crizanlizumab—a humanized, anti–P-selectin monoclonal antibody—reduced the frequency of VOCs by 45% and delayed time to first crisis by about 3 months.
Additionally, a subgroup analysis showed there was a lower frequency of VOCs with crizanlizumab at 5 mg/kg, compared with placebo, regardless of the number of prior VOCs, concomitant hydroxyurea use, or the SCD genotype.
The present post-hoc analysis took a deeper look at these observations across the same subgroups. Specifically, the investigators assessed elimination of VOCs, time to first crisis, and adverse events in 132 patients.
Crizanlizumab eliminated VOCs about seven times more frequently than did placebo in patients who had a high frequency of VOCs before the study (5 to 10 VOCs in the year prior)—28.0% and 4.2%, respectively.
Crizanlizumab eliminated VOCs about twice as often as placebo in patients with the HbSS genotype—31.9% and 17.0%, respectively—and in patients who were using concomitant hydroxyurea—33.3% and 17.5%, respectively.
Further analysis showed that crizanlizumab delayed time to first VOC across all subgroups.
In patients with the HbSS genotype, the time to first VOC was 4.07 months with crizanlizumab and 1.12 months with placebo.
In patients with a higher frequency of previous VOCs, the time to first on-study VOC was 2.43 months with crizanlizumab and 1.03 months with placebo.
In patients taking hydroxyurea, the time to first VOC was 2.43 months with crizanlizumab and 1.45 months with placebo.
Safety was comparable across subgroups.
This study was sponsored by Novartis. The authors reported financial relationships with Novartis, Bluebird Bio, AstraZeneca, and others.
Crizanlizumab can reduce vaso-occlusive crises (VOCs) across subgroups of patients with sickle cell disease (SCD), according to a post-hoc analysis of the phase 2 SUSTAIN trial.
Researchers found crizanlizumab was more effective than placebo at delaying time to first VOC and eliminating crises in patients who had numerous previous crises, exhibited the HbSS genotype, or were taking concomitant hydroxyurea.
Abdullah Kutlar, MD, of the Medical College of Georgia in Augusta, and his colleagues reported these findings in the American Journal of Hematology.
The phase 2 SUSTAIN trial previously showed that crizanlizumab—a humanized, anti–P-selectin monoclonal antibody—reduced the frequency of VOCs by 45% and delayed time to first crisis by about 3 months.
Additionally, a subgroup analysis showed there was a lower frequency of VOCs with crizanlizumab at 5 mg/kg, compared with placebo, regardless of the number of prior VOCs, concomitant hydroxyurea use, or the SCD genotype.
The present post-hoc analysis took a deeper look at these observations across the same subgroups. Specifically, the investigators assessed elimination of VOCs, time to first crisis, and adverse events in 132 patients.
Crizanlizumab eliminated VOCs about seven times more frequently than did placebo in patients who had a high frequency of VOCs before the study (5 to 10 VOCs in the year prior)—28.0% and 4.2%, respectively.
Crizanlizumab eliminated VOCs about twice as often as placebo in patients with the HbSS genotype—31.9% and 17.0%, respectively—and in patients who were using concomitant hydroxyurea—33.3% and 17.5%, respectively.
Further analysis showed that crizanlizumab delayed time to first VOC across all subgroups.
In patients with the HbSS genotype, the time to first VOC was 4.07 months with crizanlizumab and 1.12 months with placebo.
In patients with a higher frequency of previous VOCs, the time to first on-study VOC was 2.43 months with crizanlizumab and 1.03 months with placebo.
In patients taking hydroxyurea, the time to first VOC was 2.43 months with crizanlizumab and 1.45 months with placebo.
Safety was comparable across subgroups.
This study was sponsored by Novartis. The authors reported financial relationships with Novartis, Bluebird Bio, AstraZeneca, and others.
Crizanlizumab can reduce vaso-occlusive crises (VOCs) across subgroups of patients with sickle cell disease (SCD), according to a post-hoc analysis of the phase 2 SUSTAIN trial.
Researchers found crizanlizumab was more effective than placebo at delaying time to first VOC and eliminating crises in patients who had numerous previous crises, exhibited the HbSS genotype, or were taking concomitant hydroxyurea.
Abdullah Kutlar, MD, of the Medical College of Georgia in Augusta, and his colleagues reported these findings in the American Journal of Hematology.
The phase 2 SUSTAIN trial previously showed that crizanlizumab—a humanized, anti–P-selectin monoclonal antibody—reduced the frequency of VOCs by 45% and delayed time to first crisis by about 3 months.
Additionally, a subgroup analysis showed there was a lower frequency of VOCs with crizanlizumab at 5 mg/kg, compared with placebo, regardless of the number of prior VOCs, concomitant hydroxyurea use, or the SCD genotype.
The present post-hoc analysis took a deeper look at these observations across the same subgroups. Specifically, the investigators assessed elimination of VOCs, time to first crisis, and adverse events in 132 patients.
Crizanlizumab eliminated VOCs about seven times more frequently than did placebo in patients who had a high frequency of VOCs before the study (5 to 10 VOCs in the year prior)—28.0% and 4.2%, respectively.
Crizanlizumab eliminated VOCs about twice as often as placebo in patients with the HbSS genotype—31.9% and 17.0%, respectively—and in patients who were using concomitant hydroxyurea—33.3% and 17.5%, respectively.
Further analysis showed that crizanlizumab delayed time to first VOC across all subgroups.
In patients with the HbSS genotype, the time to first VOC was 4.07 months with crizanlizumab and 1.12 months with placebo.
In patients with a higher frequency of previous VOCs, the time to first on-study VOC was 2.43 months with crizanlizumab and 1.03 months with placebo.
In patients taking hydroxyurea, the time to first VOC was 2.43 months with crizanlizumab and 1.45 months with placebo.
Safety was comparable across subgroups.
This study was sponsored by Novartis. The authors reported financial relationships with Novartis, Bluebird Bio, AstraZeneca, and others.
Bacteremic sepsis in ALL tied to neurocognitive dysfunction
Bacteremic sepsis during acute lymphoblastic leukemia (ALL) treatment may contribute to neurocognitive dysfunction later in life, results of a cohort study suggest.
Pediatric ALL survivors who had sepsis while on treatment performed worse on measures of intelligence, attention, executive function, and processing speed than survivors with no sepsis history, according to study results.
Links between sepsis and impaired neurocognitive function found in this study have “practice-changing implications” for cancer survivors, investigators reported in JAMA Pediatrics.
“Prevention of infection, early recognition and appropriate management of sepsis, and preemptive neurocognitive interventions should be prioritized, because these might prevent or ameliorate neurologic damage,” said Joshua Wolf, MBBS, of St. Jude Children’s Research Hospital, Memphis, and the coauthors of the report.
The study included 212 children who, at a median age of 5 years, had received risk-adapted chemotherapy for ALL with no hematopoietic cell transplant or cranial irradiation.
Sixteen of the patients (7.5%) had a history of bacteremic sepsis during ALL therapy, according to retrospectively obtained data.
As a part of the study, all patients participated in neurocognitive testing, which was done at a median of 7.7 years after diagnosis.
Patients with a history of bacteremic sepsis performed poorly on multiple measures of neurocognitive function, as compared with all other patients, according to results of analyses that were adjusted for multiple potentially confounding factors, such as age, race, and leukemia risk category.
Although not all neurocognitive measures were significantly different between groups, survivors with a sepsis history performed worse on evaluations of spatial planning (difference, 0.78; 95% CI, 0.57-1.00), verbal fluency (0.38; 95% CI, 0.14-0.62), and attention (0.63; 95% CI, 0.30-0.95), among other measures.
This is believed to be the first published study looking at potential links between sepsis during ALL treatment and long-term neurocognitive dysfunction, investigators said. However, similar observations have been made in other patient populations, they added.
Exactly how sepsis might lead to neurocognitive deficits remains unclear.
“In the population of children with cancer, these mechanisms might be augmented by increased blood-brain barrier permeability to neurotoxic chemotherapy drugs,” the investigators said in their report.
Further study is needed to look at potential brain injury mechanisms and to validate the current findings in other ALL patient cohorts, they concluded.
The study was supported by the National Institute of Mental Health, the National Cancer Institute, and the American Lebanese Syrian Associated Charities. The researchers reported having no conflicts of interest.
Bacteremic sepsis during acute lymphoblastic leukemia (ALL) treatment may contribute to neurocognitive dysfunction later in life, results of a cohort study suggest.
Pediatric ALL survivors who had sepsis while on treatment performed worse on measures of intelligence, attention, executive function, and processing speed than survivors with no sepsis history, according to study results.
Links between sepsis and impaired neurocognitive function found in this study have “practice-changing implications” for cancer survivors, investigators reported in JAMA Pediatrics.
“Prevention of infection, early recognition and appropriate management of sepsis, and preemptive neurocognitive interventions should be prioritized, because these might prevent or ameliorate neurologic damage,” said Joshua Wolf, MBBS, of St. Jude Children’s Research Hospital, Memphis, and the coauthors of the report.
The study included 212 children who, at a median age of 5 years, had received risk-adapted chemotherapy for ALL with no hematopoietic cell transplant or cranial irradiation.
Sixteen of the patients (7.5%) had a history of bacteremic sepsis during ALL therapy, according to retrospectively obtained data.
As a part of the study, all patients participated in neurocognitive testing, which was done at a median of 7.7 years after diagnosis.
Patients with a history of bacteremic sepsis performed poorly on multiple measures of neurocognitive function, as compared with all other patients, according to results of analyses that were adjusted for multiple potentially confounding factors, such as age, race, and leukemia risk category.
Although not all neurocognitive measures were significantly different between groups, survivors with a sepsis history performed worse on evaluations of spatial planning (difference, 0.78; 95% CI, 0.57-1.00), verbal fluency (0.38; 95% CI, 0.14-0.62), and attention (0.63; 95% CI, 0.30-0.95), among other measures.
This is believed to be the first published study looking at potential links between sepsis during ALL treatment and long-term neurocognitive dysfunction, investigators said. However, similar observations have been made in other patient populations, they added.
Exactly how sepsis might lead to neurocognitive deficits remains unclear.
“In the population of children with cancer, these mechanisms might be augmented by increased blood-brain barrier permeability to neurotoxic chemotherapy drugs,” the investigators said in their report.
Further study is needed to look at potential brain injury mechanisms and to validate the current findings in other ALL patient cohorts, they concluded.
The study was supported by the National Institute of Mental Health, the National Cancer Institute, and the American Lebanese Syrian Associated Charities. The researchers reported having no conflicts of interest.
Bacteremic sepsis during acute lymphoblastic leukemia (ALL) treatment may contribute to neurocognitive dysfunction later in life, results of a cohort study suggest.
Pediatric ALL survivors who had sepsis while on treatment performed worse on measures of intelligence, attention, executive function, and processing speed than survivors with no sepsis history, according to study results.
Links between sepsis and impaired neurocognitive function found in this study have “practice-changing implications” for cancer survivors, investigators reported in JAMA Pediatrics.
“Prevention of infection, early recognition and appropriate management of sepsis, and preemptive neurocognitive interventions should be prioritized, because these might prevent or ameliorate neurologic damage,” said Joshua Wolf, MBBS, of St. Jude Children’s Research Hospital, Memphis, and the coauthors of the report.
The study included 212 children who, at a median age of 5 years, had received risk-adapted chemotherapy for ALL with no hematopoietic cell transplant or cranial irradiation.
Sixteen of the patients (7.5%) had a history of bacteremic sepsis during ALL therapy, according to retrospectively obtained data.
As a part of the study, all patients participated in neurocognitive testing, which was done at a median of 7.7 years after diagnosis.
Patients with a history of bacteremic sepsis performed poorly on multiple measures of neurocognitive function, as compared with all other patients, according to results of analyses that were adjusted for multiple potentially confounding factors, such as age, race, and leukemia risk category.
Although not all neurocognitive measures were significantly different between groups, survivors with a sepsis history performed worse on evaluations of spatial planning (difference, 0.78; 95% CI, 0.57-1.00), verbal fluency (0.38; 95% CI, 0.14-0.62), and attention (0.63; 95% CI, 0.30-0.95), among other measures.
This is believed to be the first published study looking at potential links between sepsis during ALL treatment and long-term neurocognitive dysfunction, investigators said. However, similar observations have been made in other patient populations, they added.
Exactly how sepsis might lead to neurocognitive deficits remains unclear.
“In the population of children with cancer, these mechanisms might be augmented by increased blood-brain barrier permeability to neurotoxic chemotherapy drugs,” the investigators said in their report.
Further study is needed to look at potential brain injury mechanisms and to validate the current findings in other ALL patient cohorts, they concluded.
The study was supported by the National Institute of Mental Health, the National Cancer Institute, and the American Lebanese Syrian Associated Charities. The researchers reported having no conflicts of interest.
NSAIDs’ short-term safety, IVUS beats angio, and more
, NSAIDs show cardiovascular and renal safety in the short term, a registry analysis supports use of direct oral anticoagulants over warfarin, and IVUS-guided stent placement bests angiography-led placement.
Subscribe to Cardiocast wherever you get your podcasts.
Amazon
Alexa
Apple Podcasts
Google Podcasts
, NSAIDs show cardiovascular and renal safety in the short term, a registry analysis supports use of direct oral anticoagulants over warfarin, and IVUS-guided stent placement bests angiography-led placement.
Subscribe to Cardiocast wherever you get your podcasts.
Amazon
Alexa
Apple Podcasts
Google Podcasts
, NSAIDs show cardiovascular and renal safety in the short term, a registry analysis supports use of direct oral anticoagulants over warfarin, and IVUS-guided stent placement bests angiography-led placement.
Subscribe to Cardiocast wherever you get your podcasts.
Amazon
Alexa
Apple Podcasts
Google Podcasts
