Hočkinov limfom

COVID19, Hočkinov limfom, Hronična limfocitna leukemija, Leukemije, Multipli mijelom, Nehočkinski limfom

FINDINGS FROM A RETROSPECTIVE CASE STUDY OF COVID-19 INFECTION IN CANCER PATIENTS IN WUHAN: AN EMPHASIS ON SEVERE EVENTS

Analysis of risk factors associated with admission to an intensive care unit, the use of mechanical ventilation or deathDate:30 Mar 2020Topics:Cancer in Special Situations / Population A study team composed from clinicians from three hospitals in Wuhan, China, led by Dr Min Zhou of the Department of the Respiratory and Critical Care Medicine, Tongji Hospital, performed a retrospective case study of clinical features among 28 patients with cancer and COVID-19 infection. In particular, they analyzed the risk factors associated with admission to an intensive care unit, the use of mechanical ventilation or death. Their series was associated with poor outcomes. There was increased risk of developing severe events, especially if the last antitumour treatment was within 14 days of COVID-19 diagnosis. The findings are published on 23 March 2020 in the Annals of Oncology. Like the other coronaviruses, SARS-CoV-2 primarily causes respiratory tract infection. The study team wrote that data published in The Lancet Oncology on 18 patients with cancer diagnosis from a cohort of 2007 cases with COVID-19 disease in China represents a relatively small sample with limited clinical information and high heterogeneity of the course of the disease. Therefore, critical issues concerning treatment principles for cancer patients with COVID-19 infection are unclear. There is an urgent need to answer whether cancer patients with COVID-19 infection will have distinct clinical course and worse outcomes, such as death from the infection or severe pneumonia, and whether cancer patients should receive antitumour treatments as usual. The study team aimed to explore these issues by conducting a rapid retrospective case study on critical COVID-19-infected cancer patients. They analyzed cancer patients with laboratory confirmed COVID-19. The clinical data were collected from medical records from 13 January 2020 to 26 February 2020. In total, 28 cancer patients with COVID-19 infection were included. Of those, 17 patients (60.7%) were male. Median age was 65.0 years. Lung cancer was the most frequent cancer type in the cohort with 7 patients (25.0%), followed by oesophageal cancer in 4 patients (14.3%) and breast cancer in 3 patients (10.7%). Ten patients (35.7%) were diagnosed with stage IV cancer. Eight patients (28.6%) were suspected to be from hospital-associated transmission. All the patients had a history of antitumour therapy. Within 14 days of COVID-19 diagnosis, 6 patients (21.4%) were treated by at least one kind of antitumour therapy, such as chemotherapy in 3 patients (10.7%), targeted therapy in 2 patients (7.1%), radiotherapy in 1 patient (3.6%), immunotherapy in 1 patient (3.6%); one of them received treatment combining chemotherapy and immunotherapy. There were two main clusters of patients: 8 patients (28.6%) who developed COVID-19 undergoing antitumour therapy in hospitals and 20 patients (71.4%) in their communities. In addition to cancer, 11 patients (39.2%) had at least one or more comorbidities. The following clinical features were present in studied cohort: fever in 23 patients (82.1%), dry cough in 22 patients (81%) and dyspnoea in 14 patients (50.0%), along with lymphopaenia in 23 patients (82.1%), high level of high-sensitivity C-reactive protein in 23 patients (82.1%), anaemia in 21 patients (75.0%) and hypoproteinaemia in 25 patients (89.3%). The common chest CT findings were ground-glass opacity in 21 patients (75.0%) and patchy consolidation in 13 patients (46.3%). In total, 22 patients (78.6%) received oxygen therapy, 10 patients (35.7%) were put on invasive mechanical ventilation, with 2 patients (7.1%) requiring endotracheal intubation and invasive ventilation because of progressive hypoxia. Significantly more severe cases were subjected to mechanical ventilation (non-invasive: 53.3% vs 0%, p < 0.001; invasive: 13.3% vs 0%, p < 0.001) as compared to non-severe cases. The median period of mechanical ventilation for non-invasive and invasive ventilation was 2.5 days. None of the severe patients received extracorporeal membrane oxygenation. In the series, 20 patients (71.4%) were prescribed at least one antiviral agent, while 9 patients (32.1%) received combinations of antiviral agents. Empirical antibiotic therapy was given to 23 patients (82.1%). Systemic corticosteroids were given to 15 patients (53.6%). Administration of corticosteroids was more frequent in patients with severe events (12/15, 80%) than non-severe cases (3/13, 23.1%). Seven of 8 patients with acute respiratory distress syndrome (ARDS) received systemic corticosteroids. The dosage and period of corticosteroids in the severe cases was higher than in non-severe cases, but the difference was not significant. Moreover, intravenous immunoglobin was prescribed to 12 patients (35.7%). As of 26 February 2020, 15 patients (53.6%) developed severe clinical events, 6 patients (21.4%) were admitted to intensive care unit, 10 patients (35.7%) had life-threatening complications and 8 patients (28.6%) died. Of the 10 stage IV cancer patients, 7 patients (70%) had developed severe events, while 44.4% of the non-stage IV patients had such events. Among 6 cancer patients who received antitumor treatment within 14 days of COVID-19 disease diagnosis, 5 patients (83%) developed severe events. Additionally, 11 of 13 patients (84.6%) with patchy consolidation on CT on admission had developed severe events. The most common complication was ARDS in 8 patients (28.6%), followed by septic shock in 1 patient (3.6%), and acute myocardial infarction (AMI) in 1 patient (3.6%). Two patients (7.1%) were suspected to have pulmonary embolism. Ten of 28 patients (35.7%) had been discharged with a median hospital stay of 13.5 days; 10 patients (35.7%) were still inpatients with a median stay of 19.0 days. Of the 28 patients, 8 patients (28.6%) died, with a median time of 16.0 days from admission to death. The cause of death included ARDS in 5 patients (62.5%), followed by pulmonary embolism in 1 patient (12.5%), septic shock in 1 patient (12.5%) and AMI in 1 patient (12.5%). In univariate Cox proportional hazards model, cancer patients who received antitumour treatment within 14 days of COVID-19 diagnosis had a higher risk of developing severe events. Moreover, patchy consolidation on the first CT on admission suggested an elevated risk of developing severe events than those cases without consolidation. Similar results were observed in the multivariate-adjusted Cox proportional hazards model after being adjusted for age and gender. If the last antitumour treatment was within 14 days, it significantly increased the risk

Hočkinov limfom, Hronična limfocitna leukemija, Nehočkinski limfom

Body size and obesity during adulthood, and risk of lympho-haematopoietic cancers: an update of the WCRF-AICR systematic review of published prospective studies

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

Hočkinov limfom, Hronična limfocitna leukemija, Nehočkinski limfom

BMT Societies Issue Recommendations on Posttransplant Maintenance in HL/NHL

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

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A small change makes a big difference in Hodgkin lymphoma

At first glance, it may not seem like much, a post hoc retrospective analysis of outcomes for patients with different levels of 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) scans after 2 cycles of chemotherapy for advanced-stage Hodgkin lymphoma (HL). But in fact, the results reported by Kobe et al1 in this issue of Blood have profound and beneficial consequences for 1 in 4 patients with advanced-stage HL who receive the intensive escalated-dose bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP) regimen. Second only to the relatively recent arrival of novel, targeted agents for the treatment of relapsed and refractory disease,2 the introduction of PET represents the most important improvement in the management of HL in the last decade. Observational studies consistently found a very high prognostic value of early interim PET, suggesting that early PET could identify patients with excellent response who might benefit from a reduction of treatment intensity or duration without loss of efficacy.3,4 This would reduce the risk of overtreatment, which is an important challenge in a disease in which the vast majority of patients are young and curable and the cumulative late toxicities of treatment are substantial.5 PET could also identify poor responders who might benefit from intensification of treatment. Subsequently, a number of interventional studies have shown that early PET response–adapted therapy can reduce the overall treatment burden and improve progression-free survival in patients with advanced-stage HL who receive first-line treatment with the most commonly used regimen consisting of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD).6 Studies of early interim PET in cohorts treated with eBEACOPP have shown the same high negative predictive values as in cohorts treated with ABVD, but the positive predictive values have been lower. This is probably a consequence of the lower a priori risk of treatment failure in patients treated with this more intensive regimen. In the experimental arm of the German Hodgkin Study Group (GHSG) HD18 study, duration of treatment was reduced in patients who were PET negative after 2 cycles of eBEACOPP. The study showed noninferiority of abbreviated treatment of early PET-negative patients which, at the same time, resulted in a very clear reduction in the risk of acute treatment-related toxicity and the risk of secondary acute leukemias and myelodysplastic syndromes, the most feared complications related to eBEACOPP.7 After observing the important therapeutic consequences of interim PET, much effort was given to establishing uniform criteria for interpreting and reporting interim PET. These efforts led to agreement on a 5-point scale in which tumor FDG uptake is graded according to tracer uptake in different reference areas. This scale, named after the French seaside town Deauville where it was first established, was included in the international consensus guidelines for imaging and response assessment in lymphoma.8 Several studies have shown that the best cutoff between a negative and positive scan was between Deauville scores 3 and 4 (DS3 and DS4), which corresponds to the background uptake in the liver. Compared with a lower threshold, this results in a higher prognostic accuracy and at the same time a lower interobserver variation.9,10 Nevertheless, in the HD18 study, it was decided to include only DS1 and DS2 as negative results to reduce the potential risk of undertreatment. The report by Kobe et al is by far the largest study of early interim PET in advanced-stage HL. The results are very clear, showing no difference in progression-free and overall survival between patients with DS1-2 and DS3, respectively, when they were treated on the standard arm of the study with 6 cycles of eBEACOPP. Because ∼25% of all advanced-stage HL patients had FDG uptake with DS3 on early interim PET, the proportion of patients with a negative scan increased from 52% to 76% when the threshold between a negative and a positive result was lowered. The authors thoroughly stress that there is no direct evidence that we can reduce treatment of patients with DS3 on interim PET without impairing efficacy. However, the indications are so strong that the authors (as well as the GHSG) recommend restricting treatment to 4 cycles of eBEACOPP for patients with DS3 as well as for patients with DS1-2 on early interim PET. The GHSG has provided a wealth of evidence from 4 decades of randomized clinical studies. Most of their recommendations are based on strong evidence from those randomized clinical studies. The current change is an exception for which the group should be commended. The ongoing GHSG HD21 study for advanced-stage HL is a randomized study in which patients in the standard arm receive early PET response–adapted treatment based on the results of the HD18 study. So patients who are PET negative after 2 cycles of eBEACOPP receive a total of 4 treatment cycles and not 6 cycles, which was the previous standard. The definition of PET negative includes DS1, DS2, and DS3. In this way, the HD21 study hopefully will demonstrate that it is safe to include patients with a DS3 score in the PET-negative group and treat them accordingly. The study by Kobe et al represents an important improvement for patients with advanced-stage HL who are treated with eBEACOPP. At the same time, it is an inspiring example of how good and thorough retrospective analyses of clinical trials can sometimes provide data of the highest importance and clinical relevance. And in this case, provide new fuel for the long-lasting debate about ABVD vs eBEACOPP for first-line treatment of advanced-stage HL. Source: Blood 2018 132:2214-2215

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What are the effects of different doses and treatments for limited stage classical Hodgkin’s lymphoma?

This study investigated the effects of increasing the initial dose of chemotherapy in patients with classical Hodgkin’s lymphoma (cHL). The main finding was that it is necessary to assess each treatment plan based on the patient’s individual disease. Chemotherapy plus stem cell transplant (SCT; meaning the transfer of stem cells) and radiation are common treatments for cHL. Event free survival (EFS – didn’t show a specific cancer symptom over a specific period of time), positron-emission tomography (PET – used to diagnose and monitor cancer) scanning and red blood cell sedimentation (blood test for inflammation) are commonly monitored in trials for new therapies/regimes for cHL Different doses and combinations of therapies have different effects in cHL. . It is necessary to investigate the effects of different treatment strategies for cHL. Two hundred and seventy-eight patients with cHL were studied.  Patients who had received the minimum chemotherapy alone and that had reached remission (no signs of active cancer) were included. EFS and red blood cell sedimentation rate were monitored and PET scanning was carried out. After 4 years, 49% of patients had received the minimum chemotherapy without radiation. Remission was achieved by 88.8% of patients without receiving high dose chemotherapy plus SCT or high dose radiation. Almost 100% of patients survived. Nearly 76% of patients with nodular sclerosis (a common type of cHL) had event free survival. A slow red blood cell sedimentation rate was linked to greater EFS. Negative PET scan results after 1 cycle of chemotherapy was linked with event free survival. The study conlcuded that lower doses of chemotherapy were effective in patients who had negative PET scan results and slow red blood cell sedimentation. Higher doses of chemotherapy should be considered for patients with nodular sclerosis plus high ESR or positive PET scan results Only patients up to the age of 21 were included in this study. Therefore the results may not be representative of patients over 21.

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