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No data are available regarding obesity and outcome in Chronic Lymphocytic Leukemia (CLL). We analyzed 263 patients from the AGMT CLL‐8a Mabtenance trial for the impact of obesity. The trial included patients after rituximab‐containing induction treatment in first or second line that had achieved at least a PR. A randomization to rituximab maintenance treatment (375 mg/m2 q3 months for 2 years) vs observation was performed. In this cohort 22% of the patients (58/263) were classified as obese. The baseline response to induction treatment was inferior in obese patients with a lower CR rate (43.1% vs 60.5% in obese vs non‐obese, P = 0.018) and with a lower rate of patients achieving MRD negativity after chemoimmunotherapy induction treatment (19.6% vs 35.8%, P = 0.02). The PFS outcome of obese patients was significantly worse in the observation group of the trial (24 vs 39 months median PFS, P = 0.03). However, in the rituximab maintenance group the outcome for obese vs non‐obese was not different (P = 0.4). In summary, obesity was overall associated with a worse outcome of chemoimmunotherapy induction. However, rituximab maintenance treatment seems to be able to overcome this negative effect. [ABSTRACT FROM AUTHOR]

Over the past decade, the treatment of patients with chronic lymphocytic leukemia (CLL) has been improved by several new cytostatic agents and monoclonal antibodies. This development has resulted in higher response rates and more profound levels of immunosuppression than with previously used treatments. With the intrinsic immune defect of CLL, the degree and quality of immunosuppression is thus substantially different from that observed during the treatment of other indolent lymphomas and warrants special consideration. Infection with or reactivation of viral diseases such as herpes simplex, varicella zoster, cytomegalovirus (CMV), Epstein-Barr virus (EBV), hepatitis B and C or JC virus has become a more frequent problem in the management of these patients. However, most data are derived from observational studies, and only a few interventional trials have been planned and reported. In this review, we summarize the available data, discuss several treatment and management options and offer some recommendations. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancers, such as chronic lymphocytic leukemia, frequently acquire consecutive somatic mutations in the genome, which contribute to disease progression and treatment resistance. Activation-induced deaminase is an enzyme responsible for generating the highly diverse B cell repertoire but it can also induce substantial collateral damage within the genome of cells. Hence, it is important to assess whether AID contributes to cancer mutations and to the course of disease. This research shows that AID contributes to the acquisition of somatic cancer-specific mutations in a mouse model for chronic lymphocytic leukemia reflected in prolonged overall survival of leukemic mice lacking AID expression. These data should initiate future studies to assess the effect of AID inhibition on the occurrence of drug resistance. Adaptive somatic mutations conferring treatment resistance and accelerated disease progression is still a major problem in cancer therapy. Additionally in CLL, patients receiving novel, efficient drugs frequently become treatment refractory and eventually relapse. Activation-induced deaminase (AID) is a cytosine deaminase that catalyzes somatic hypermutation of genomic DNA at the immunoglobulin locus in activated B cells. As considerable off-target mutations by AID have been discerned in chronic lymphocytic leukemia, it is essential to investigate to which extent these mutations contribute to disease progression to estimate whether AID inhibition could counteract drug resistance mechanisms. In this study, we examined the TCL1 mouse model for CLL on an AID pro- and deficient background by comparing disease development and mutational landscapes. We provide evidence that AID contributes to the acquisition of somatic cancer-specific mutations also in the TCL1 model and accelerates CLL development particularly in the transplant setting. We conclude that AID is directly determining the fitness of the CLL clone, which prompts further studies to assess the effect of AID inhibition on the occurrence of drug resistance. [ABSTRACT FROM AUTHOR]