Risk of progression in chronic phase‐chronic myeloid leukemia patients eligible for tyrosine kinase inhibitor discontinuation: Final analysis of the TFR‐PRO study
Giovanni Paolo Maria ZambrottaFranck E. NicoliniSarit AssoulineLambert BusqueEster PungolinoElisabetta AbruzzeseMaria Cristina MiggianoChiara ElenaAlberto Álvarez‐LarránAna TrigueroAlessandra IurloCristina BucelliMarco CerranoIsabella CapodannoFrancesca LunghiPhilipp le CoutreSara GalimbertiGiovanni CaocciMargherita MaffioliFabio StagnoSusanne SaußeleRocco PiazzaBrian J. DrukerCarmen FavaVeronica GuglielmanaFederica ColomboLaura AntoliniCarlo Gambacorti‐Passerini
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Abstract:
Disease progression to accelerated/blast phase (AP/BP) in patients with chronic phase chronic myeloid leukemia (CP-CML) after treatment discontinuation (TD) has never been systematically reported in clinical trials. However, recent reports of several such cases has raised concern. To estimate the risk of AP/BP among TD-eligible patients, we conducted TFR-PRO, a cohort retro-prospective study: 870 CP-CML patients eligible for TD formed a discontinuation cohort (505 patients) and a reference one (365 patients). The primary objective was the time adjusted rate (TAR) of progression in relation to TD. Secondary endpoints included the TAR of molecular relapse, that is, loss of major molecular response (MMR). With a median follow up of 5.5 years and 5188.2 person-years available, no events occurred in the TD cohort. One event of progression was registered 55 months after the end of TD, when the patient was contributing to the reference cohort. The TAR of progression was 0.019/100 person-years (95% CI [0.003-0.138]) in the overall group; 0.0 (95% CI [0-0.163]) in the discontinuation cohort; and 0.030 (95% CI [0.004-0.215]) in the reference cohort. These differences are not statistically significant. Molecular relapses occurred in 172/505 (34.1%) patients after TD, and in 64/365 (17.5%) patients in the reference cohort, p < .0001. Similar rates were observed in TD patients in first, second or third line of treatment. CML progression in patients eligible for TD is rare and not related to TD. Fears about the risk of disease progression among patients attempting TD should be dissipated.Keywords:
Discontinuation
Vitamin D deficiency is less common among HIV-infected African–American men than in a matched cohort
The aim of this study was to compare the prevalence of vitamin D sufficiency and deficiency in a HIV-infected cohort of African-American men with that of a general population. We found median vitamin D concentrations were significantly greater in the HIV-infected cohort, 18 ng/ml as compared to the National Health and Nutrition Examination Survey cohort, 14 ng/ml (P ≤ 0.0001). Thus, factors other than measured vitamin D are likely to be responsible for higher rates of bone disease in this population.
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Abstract Dairy product intake was suggested to reduce the risk of gastrointestinal cancers. This study investigated the association between dairy product intake and the risk of pancreatic cancer (PAC) using a prospective cohort study and meta-analysis of prospective cohort studies. First, we included 59 774 people aged 40–79 years from the Japan Collaborative Cohort Study (JACC Study). The Cox regression was used to compute the hazard ratios (HR) and 95 % CI of incident PAC for individuals who reported the highest intakes of milk, cheese and yogurt compared with not consuming the corresponding dairy products. Then, we combined our results with those from other four prospective cohort studies that were eligible after searching several databases, in a meta-analysis, using the fixed-effects model before evaluating publication bias and heterogeneity across studies. In the JACC Study, the highest v . no intakes of milk, cheese and yogurt were not associated with the reduced risk of PAC after a median follow-up of 13·4 years: HR (95 % CI) = 0·93 (0·64, 1·33), 0·91 (0·51, 1·62) and 0·68 (0·38, 1·21), respectively. The results did not significantly change in the meta-analysis: 0·95 (0·82, 1·11) for milk, 1·16 (0·87, 1·55) for cheese and 0·91 (0·79, 1·05) for yogurt. The meta-analysis showed no signs of publication bias or heterogeneity across studies. To conclude, consumption of milk, cheese and yogurt was not associated with the risk of PAC either in the JACC Study or the meta-analysis.
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OBJECTIVES: To examine the cancer risk of shoe manufacturing workers and evaluate whether the risk was associated with exposure to leather dust and solvents. METHODS: Data from two historical cohort studies of shoe workers were expanded and analysed in parallel. A total of 4215 shoemakers from England contributing 103 726 person-years at risk and 2008 shoemakers from Florence, Italy, contributing 54,395 person-years at risk were included in the analysis. Exposure to leather dusts and solvents from glues was evaluated on the basis of job title information. Standardised mortality ratios (SMR) were calculated as ratios of observed deaths (Obs) over expected derived from national mortalities. RESULTS: Overall mortality was lower than expected in both cohorts (English cohort: Obs 3314, SMR 81, 95% confidence interval (95% CI) 78-84; Florence cohort: Obs 333, SMR 87, 95% CI 78-97). An increased risk of nasal cancer was found (English cohort: Obs 12, SMR 741; Florence cohort: Obs 1, SMR 909). 10 of the 13 cases occurred among English workers employed in the manufacture of welted boots (SMR 926, 95% CI 444-1703), a sector of the industry thought to have had the highest exposure to leather dust. Mortality from leukaemia was not increased in the English cohort (Obs 16, SMR 89), but was increased in the Florence cohort (Obs 8, SMR 214, 95% CI 92-421); and the highest risk was found among shoe workers in Florence who were first exposed between 1950 and 1959 when exposure to benzene was substantial (Obs 3, SMR 536, 95% CI 111-1566). Some evidence for an excess risk of stomach, bladder, and kidney cancer, as well as multiple myeloma and non-Hodgkin's lymphoma was also found in the Florence cohort only among workers employed in jobs with the highest exposure to solvents. CONCLUSIONS: These findings confirm the associations between exposure to leather dust and nasal cancer and between exposure to benzene and leukaemia in the shoe manufacturing industry and suggest that the risk of other cancers may be increased among workers exposed to solvents or glues.
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Introduction: Vitamin D deficiency has been documented across all age groups and both sexes from India. However, there is paucity of data on vitamin D deficiency in a particular cohort of population. Objectives: To assess the vitamin D status in a cohort of physicians and diabetologists in Kolkata. Material and Methods: An observational cross sectional study carried out in the month of December 2011 in a cohort of 40 physicians and diabetologists in Kolkata. Results: A total of 40 subjects were studied. Mean age of the cohort was 52.22 ± 10.91. Mean serum vitamin D level was 13.02 ± 4.77 ng/ml. Nearly 92.5% and 5.0% of subjects had vitamin D deficiency and insufficiency, respectively. Conclusions: Vitamin D deficiency is highly prevalent in physicians and diabetologists in Kolkata.
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Dairy intake was suggested to reduce the risk of gastrointestinal cancers. This study investigated the association between dairy intake and the risk of pancreatic cancer (PAC) using a prospective cohort study and meta-analysis of prospective cohort studies. First, we included 59,774 people aged 40-79 years from the Japan Collaborative Cohort Study (JACC Study). The Cox regression was used to compute the hazard ratios (HRs) and 95% confidence intervals (CIs) of incident PAC for individuals who reported the highest intakes of milk, cheese, and yogurt compared with not consuming the corresponding dairy products. Then, we combined our results with those from other four prospective cohort studies that were eligible after searching several databases, in a meta-analysis, using the fixed-effects model before evaluating publication bias and heterogeneity across studies. In the JACC study, the highest versus no intakes of milk, cheese, and yogurt were not associated with the reduced risk of PAC after a median follow-up of 13.4 years: HRs (95% CIs)= 0.93 (0.64, 1.33), 0.91 (0.51, 1.62), and 0.68 (0.38, 1.21), respectively. The results did not significantly change in the meta-analysis: 0.95 (0.82, 1.11) for milk, 1.16 (0.87, 1.55) for cheese, and 0.91 (0.79, 1.05) for yogurt. The meta-analysis showed no signs of publication bias or heterogeneity across studies. To conclude, consumption of milk, cheese, and yogurt was not associated with the risk of PAC either in the JACC study or the meta-analysis.
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BackgroundThe cross-sectional HIV care continuum is widely used to assess the success of HIV care programmes among populations of people with HIV and the potential for ongoing transmission. We aimed to investigate whether a longitudinal continuum, which incorporates loss to follow-up and mortality, might provide further insights about the performance of care programmes.MethodsIn this longitudinal cohort study, we included individuals who entered the UK Collaborative HIV Cohort (CHIC) study between Jan 1, 2000, and Dec 31, 2004, and were linked to the national HIV cohort database (HIV and AIDS Reporting System). For each month during a 10 year follow up period, we classified individuals into one of ten distinct categories according to engagement in care, antiretroviral therapy (ART) use, viral suppression, loss to cohort follow-up and loss to care, and mortality, and assessed the proportion of person-months of follow-up spent in each stage of the continuum. 5 year longitudinal continuums were also constructed for three separate cohorts (baseline years of entry 2000–03, 2004–07, and 2008–09) to compare changes over time.FindingsWe included 12 811 people contributing 1 537 320 person-months in our analysis. During 10 years of follow-up, individuals spent 811 057 (52·8%) of 1 537 320 person-months on ART. Of the 811 057 person-months spent on ART, individuals had a viral load of 200 copies per mL or less for 607 185 (74·9%) person-months. 10 years after cohort entry, 3612 (28·1%) of 12 811 individuals were lost to follow-up, 954 (26·4%) of whom had transferred to a non-CHIC UK clinic for care. By 10 years, 759 (5·9%) of 12 811 participants who entered the cohort had died. Loss to follow-up decreased and the proportion of person-months that individuals spent virally suppressed increased over calendar time.InterpretationLoss to follow-up in HIV care programmes was high and rates of viral suppression were lower than previously reported. Complementary information provided by a longitudinal continuum might highlight areas for intervention along the HIV care pathway, however, transfers outside the cohort must be accounted for.FundingMedical Research Council, UK.
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The E3N (Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale) cohort was initiated in 1990 to investigate therisk factors associated with cancer and other major non-communicable diseases in women. The participants were insured through a national health system that primarily covered teachers, and were enrolled from 1990 after returning baseline self-administered questionnaires and providing informed consent. The cohort comprised nearly 100,000 women with baseline ages ranging from 40 to 65 years. Follow-up questionnaires were sent approximately every 2-3 years after the baseline and addressed general and lifestyle characteristics together with medical events (cancer, cardiovascular diseases, diabetes, depression, fractures and asthma, among others). The follow-up questionnaire response rate remained stable at approximately 80%. A biological material bank was generated and included blood samples collected from 25,000 women and saliva samples from an additional 47,000 women. Ageing among the E3N cohort provided the opportunity to investigate factors related to age-related diseases and conditions as well as disease survival. The new E4N complementary cohort (Epidemiology 4 kNowledge), which comprises the children and grandchildren of the E3N cohort as well as the children's fathers, will allow researchers to investigate key life periods during which exposures to environmental factors most strongly influence the later disease risk. The E3N and E4N cohort data will be used to investigate diseases and risk factors through a transgenerational approach. Requests for collaborations are welcome, particularly those in conjunction with rare diseases.
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ABSTRACT Purpose The Mother and Child Covid-19 study is a cohort recruiting pregnant women and their children in Cantabria, North of Spain, during COVID-19 pandemic in order to ascertain Consequences of SARS-CoV-2 infection on pregnant women and their descendants. This article reports the cohort profile and preliminary results as recruitment is still open. Participants Three sub-cohorts can be identified at recruitment. Sub-cohort 1 includes women giving birth between 23 rd March and 25 th May 2020; they have been retrospectively recruited and could have been exposed to COVID-19 only in their third trimester of pregnancy. Sub-cohort 2 includes women giving birth from 26 th May 2020 on; they are being prospectively recruited and could have been exposed to COVID-19 in both their second and third trimesters of pregnancy. Sub-cohort 3 includes women in their 12 th week of pregnancy prospectively recruited from 26 th May 2020 on; they could have been exposed to COVID-19 anytime in their pregnancy. All women are being tested for SARS-CoV-2 infection using both RT-PCR for RNA detection and ELISA for anti-SARS-CoV-2 antibodies. All neonates are being tested for antibodies using immunochemoluminiscency tests; if the mother is tested positive for SARS-CoV-2 RNA, a naso-pharyngeal swab is also obtained from the child for RT-PCR analysis. Findings to date As of 22 nd October, 1167 women have been recruited (266, 354 and 547 for sub-cohorts 1, 2 and 3, respectively). Fourteen women tested positive to SARS-CoV-2 RNA by the day of delivery. All fourteen children born from these women tested negative for SARS-CoV-2 RNA. Future plans Children from women included in sub-cohort 3 are expected to be recruited by the end of 2020. Children will be followed-up for one year in order to ascertain the effect that COVID-19 on their development. ARTICLE SUMMARY Strengths and limitations Strengths This cohort would ascertain the effect of COVID-19 in both mother and children whatever the trimester of the infection. It would also compare health care provided to pregnant women during the COVID-19 pandemic with that provided in the same hospital before the emergence of COVID-19. The cohort is recruited in Spain, one of the developed countries earlier and more affected by COVID-19. Limitations The study could be underpowered according to the prevalence reported in a Spanish national study. Information regarding exposure to people infected by SARS-CoV-2 or risk activities is self-reported.
Pandemic
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Cohort Profile : The Epidemiology of Chronic Diseases and Multimorbidity. The EpiChron Cohort Study
Multimorbidity
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