Hočkinov limfom

Overweight and obesity are a global health problem. During the last 40 years, the number of obese adults increased from 100 million in 1975 (69 million women, 31 million men) to 671 million in 2016 (390 million women, 281 million men) [1]. Excess weight and obesity have been linked to several chronic diseases including cardiovascular disease [2, 3], diabetes [3] and many types of cancers including lympho-haematopoietic cancers [4]. The age standardized incidence rates worldwide (per 100 000 inhabitants) were estimated of 1.0 for Hodgkin’s lymphoma (HL), 6.7 for non-Hodgkin’s lymphoma (NHL), 2.1 for multiple myeloma (MM) and 5.7 for leukaemia in 2018 [5]. Although, lympho-haematopoietic cancers are not as frequent as other cancers such as lung, breast, colorectal and prostate cancers, it is very important to investigate their association with overweight and obesity, which are the major public health issues. Consequently findings can add to the existing literature about the importance of lifestyle modification specifically weight management in prevention of haematological cancer incidence and mortality [4]. Previous meta-analyses published up to 2014, showed that greater body mass index (BMI) may increase the risk of HL [6], NHL [6], diffuse large beta-cell lymphoma (DLBCL) [7], myeloma [8] and leukaemia [9]. Since the publication of these metaanalysis, several additional large prospective studies with large number of cases have been published [10–16]. The accumulated evidence has greatly enhanced the investigation of how these modifiable risk factors influence the development of the many different types of lympho-haematopoietic cancers. Moreover, whether BMI in early adulthood (age 18–21 years), height and abdominal obesity increase the risk of lympho-haematopoietic cancers have not been summarized in a meta-analysis. Therefore, we conducted a systematic literature review and meta-analysis of prospective studies of BMI, BMI in early adulthood, height, weight, waist circumference (WC) and waist-to-hip ratio (WHR), and the risk of lymphoma, myeloma and leukaemia, and their main types to provide an up-to-date and comprehensive assessment of the existing evidence. We aimed to clarify the strength and shape of dose–response relationship between the general and abdominal adiposity and lympho-haematopoietic cancers and investigate any potential differences by sub-sites, sex, geographical locations, size of cohort, number of cases, years of follow-up, exposure assessment methods and adjustment for potential confounders. Search strategy and inclusion criteria The CUP team at Imperial College London searched in PubMed for studies on anthropometric measures including BMI, BMI in early adulthood (age 18–21 years), height, weight, WC and WHR, and lympho-haematopoietic cancer risk up to December 2017. The specific search criteria and the review protocol can be seen in supplementary materials, available at Annals of Oncology online. Study selection Our study selection was restricted to cohort (prospective, retrospective, case–cohort or nested case–control studies) studies which investigated the link between anthropometric measures and lympho-haematopoietic cancer risk and mortality, and reported estimates of the relative risk (RR) (e.g. hazard ratio, risk ratio or odds ratio) and 95% confidence intervals (CIs) for the exposures of interest [BMI, BMI in early adulthood (aged 18– 21 years), weight, WC and WHR]. In case of studies reporting only categorical results, number of cases and denominator data (person-years of follow-up or number of subjects) were required for inclusion in the meta-analysis. If there were multiple publications from the same study, the newest publication that included the largest number of cases was selected. Data extraction We extracted the following data from each study: authors, year of publication, country of origin, cancer type, length of study and loss of follow-up, sample size, numbers of cases and population at risk/controls, age, sex and other characteristics, anthropometric measures, RRs and 95% CIs or P-values for each exposure category and adjustment variables. A second reviewer checked at least 10% of the work. Statistical analysis We calculated the summary RRs and 95% CIs using random-effect models that takes into account heterogeneity between studies [17]. Q and I 2 statistics were used to determine heterogeneity [18], potential sources of which were explored in stratified analyses by sex, geographical location, exposure assessment methods, years of follow-up, number of cases, size of cohort and adjustments for confounders including alcohol consumption, smoking and physical activity. We used RR estimates and CIs for continuous increments directly from the articles if provided, and for studies that only reported categorical data, dose–response associations and 95% CIs were derived using generalized least-squares for trend estimation [19], which required the RRs and CIs associated with at least three categories of anthropometric measures, and the number of cases and non-cases or person-years of follow-up per category to be available. If only the total number of cases or person-years was reported in the articles, and the exposure was categorized in quantiles, the distribution of persons or person-years was calculated by dividing the total number of persons or person-years by the number of quantiles. We used the mean or median values per each anthropometric category if available in the articles, or the midpoint was calculated for studies that only reported a range by category. If the range of the highest or lowest category was open-ended, its width was assumed to be the same as the adjacent category. In case of close-ended lowest and highest categories with category widths substantially greater than those of the middle-categories (e.g. highest category of 35–60 kg/m2 of BMI), the Cheˆne and Thompson [20] method was used to estimate the midpoints. The Hamling method was used to recalculate the RR estimates when the first category was not used as reference [19]. If the results were reported for men and women separately, they were combined using a fixed effects meta-analysis before being pooled with other studies in linear, but not non-linear, analyses. We assessed small-study effects, such as publication bias, by using funnel plots and Egger’s test [21]. We assessed a potential nonlinear dose–response association between anthropometric measures and risk of lympho-haematopoietic cancers when we had 3 studies by calculating restricted cubic splines for each study, using three fixed knots at 10th, 50th and 90th percentiles of distribution of the exposure to account for a wider exposure range

The American Society for Blood and Marrow Transplantation (ASBMT), Center for International Blood and Marrow Transplant Research (CIBMTR), and European Society for Blood and Marrow Transplantation (EBMT) have released consensus recommendations on the use of maintenance therapies after autologous transplantation for patients with Hodgkin (HL) or non-Hodgkin lymphoma (NHL).1 Use of maintenance therapy as a therapeutic strategy in posttransplant patients with HL and NHL is increasing in frequency, according to panel member Mehdi Hamadani, MD, of CIBMTR and Medical College of Wisconsin in Milwaukee. This joint panel was tasked with reviewing available data from clinical trials and summarizing evidence about the contemporary use of maintenance therapy in these patients to help guide therapy in a rapidly advancing field. “Clinical trials evaluating maintenance treatments in lymphoma patients undergoing autologous transplantation cannot keep pace with the speed of drug development; which effectively means, by the time these trials are published the results are no longer applicable to modern patient population[s],” Dr Hamadani told Cancer Therapy Advisor. For example, the large AETHERA clinical trial of brentuximab vedotin consolidation after autologous transplant in high-risk patients with HL showed that patients derived a disease-free survival benefit from that therapy.2 However, 1 of the main eligibility criteria for that trial was that patients could not have had prior exposure to brentuximab vedotin. “The problem is that in 2018, brentuximab got approval for frontline therapy in HL and is also now commonly used in second-line therapy,” Dr Hamadani said. “The population that the AETHERA trial used is becoming less relevant in the real world and we have no trial data available on how to handle those patients.” To issue its recommendations, the panel used the RAND-modified Delphi method, which generates consensus statements where at least 75% of a panel vote in favor of a recommendation. The panel issued 22 consensus recommendations. Several grade A recommendations, indicating good research-based evidence to support the recommendation, are discussed below. The first consensus statement for HL was use of post-autologous hematopoietic stem cell transplantation (HCT) consolidation/maintenance with brentuximab vedotin for 16 cycles in brentuximab vedotin-naive classic HL with at least 1 or more high-risk features as defined by the AETHERA study. A second grade A recommendation was rituximab maintenance therapy in patients with mantle cell lymphoma undergoing auto-HCT after first-line therapy. In these patients, a randomized trial has shown improved progression-free and overall survival with this maintenance regimen compared with observation alone.3 Rituximab maintenance was also recommended in rituximab-naive patients with follicular lymphoma. This recommendation was based primarily on data from the EBMT study,4 which showed that rituximab maintenance after transplant was safe and significantly prolonged progression-free (but not overall) survival. “However, the panel acknowledges that rituximab-naive status at the time of auto-HCT in patients with FL in the current era would be rare, thus limiting the clinical impact of this statement,” the panelists wrote. According to Henry Chi Hang Fung, MD, FACP, director of the Fox Chase-Temple University Hospital Bone Marrow Transplant Program in Philadelphia, Pennsylvania, these recommendations do not necessarily offer up any new data, but instead represent the opinion of bone marrow transplant experts. “These are all based on studies that have already been published, some quite some time ago,” Dr Fung noted. “Because these are from multiple transplant societies, the target audience is definitely transplant doctors, who are highly specialized.” “It is good to get everyone on the same page with recommendations like these, where there is consensus, and of equal importance are the areas where there is no consensus, like in DLBCL [diffuse large B-cell lymphoma],” Dr Fung said. Dr Fung was referring to a final grade A consensus statement recommending against post-transplant maintenance therapy in patients with DLBCL. According to Dr Hamadani, in patients with DLBCL, some clinicians may give maintenance therapy off-label, but there is a lack of evidence base for this. “Maintenance therapies, even with older drugs like rituximab, are not free from side effects and are expensive,” Dr Hamadani said. “We reviewed all trials looking at rituximab after transplant in DLBCL and the studies were negative. They don’t show any survival benefit.” Ongoing clinical trials looking at target therapies in DLBCL may change this recommendation in the future, but clinical trial data are not yet mature.   Source: www.cancertherapyadvisor.com