No abstract

R-FC significantly improved the outcome of patients with previously treated CLL.

The addition of cladribine to the standard induction regimen is associated with increased rate of complete remission and improved survival of adult patients with AML.

The aim of the study was to investigate whether interleukin-10 (IL-10) genetic polymorphisms influence this cytokine production as well as the incidence and outcome of diffuse large B-cell lymphoma (DLBCL). The frequency of IL-10 -1082G allele was found to be higher in 199 patients with DLBCL as compared with 112 control subjects (0.47 versus 0.39, P ‫؍‬ .043). Increased serum levels of IL-10 were associated with adverse prognostic factors and poor DLBCL outcome. The frequencies of IL-10 -819T and IL-10 -592A alleles were lower in patients with elevated IL-10 serum levels (0.155 versus 0.32, P ‫؍‬ .14).

BackgroundRituximab is used in the treatment of CD20+ B cell lymphomas and other B cell lymphoproliferative disorders. Its clinical efficacy might be further improved by combinations with other drugs such as statins that inhibit cholesterol synthesis and show promising antilymphoma effects. The objective of this study was to evaluate the influence of statins on rituximab-induced killing of B cell lymphomas.Methods and FindingsComplement-dependent cytotoxicity (CDC) was assessed by MTT and Alamar blue assays as well as trypan blue staining, and antibody-dependent cellular cytotoxicity (ADCC) was assessed by a 51Cr release assay. Statins were found to significantly decrease rituximab-mediated CDC and ADCC of B cell lymphoma cells. Incubation of B cell lymphoma cells with statins decreased CD20 immunostaining in flow cytometry studies but did not affect total cellular levels of CD20 as measured with RT-PCR and Western blotting. Similar effects are exerted by other cholesterol-depleting agents (methyl-β-cyclodextrin and berberine), but not filipin III, indicating that the presence of plasma membrane cholesterol and not lipid rafts is required for rituximab-mediated CDC. Immunofluorescence microscopy using double staining with monoclonal antibodies (mAbs) directed against a conformational epitope and a linear cytoplasmic epitope revealed that CD20 is present in the plasma membrane in comparable amounts in control and statin-treated cells. Atomic force microscopy and limited proteolysis indicated that statins, through cholesterol depletion, induce conformational changes in CD20 that result in impaired binding of anti-CD20 mAb. An in vivo reduction of cholesterol induced by short-term treatment of five patients with hypercholesterolemia with atorvastatin resulted in reduced anti-CD20 binding to freshly isolated B cells.ConclusionsStatins were shown to interfere with both detection of CD20 and antilymphoma activity of rituximab. These studies have significant clinical implications, as impaired binding of mAbs to conformational epitopes of CD20 elicited by statins could delay diagnosis, postpone effective treatment, or impair anti-lymphoma activity of rituximab.

Background CPX-351 is a liposome-encapsulated fixed-molar ratio formulation of cytarabine and daunorubicin that exploits molar ratio-dependent drug-drug synergy to enhance anti-leukemic efficacy. Methods This Phase II study randomized 125 patients 2:1 to CPX-351 or investigator’s choice of first salvage chemotherapy. Patients with acute myeloid leukemia in first relapse after initial CR lasting ≥1month were stratified per European Prognostic Index (EPI) into favorable, intermediate, and poor-risk groups based upon duration of first CR, cytogenetics, age, and transplant history. Control salvage treatment was usually based on cytarabine and anthracycline, often with one or more additional agents. Survival at 1-year was the primary efficacy endpoint. Results Patient characteristics were well balanced between the two study arms. Improvements in efficacy outcomes were observed following CPX-351, but did not meet prospectively defined statistical criteria for 1-year survival improvement in the overall population. Subset analyses of the EPI-defined poor-risk strata demonstrated higher response rates (39.3% vs. 27.6%), improvements in event-free survival (HR=0.63, p=0.08) and overall survival (HR=0.55, p=0.02). Also, 60-day mortality was lower in the CPX-351 study arm for poor-risk patients (16.1% vs. 24.1%). Conclusion Taken together, the data suggest possible improved outcome in CPX-351-treated first relapse AML patients with EPI-defined poor-risk disease.

SummaryThe treatment of adults with Philadelphia-negative acute lymphoblastic leukaemia (ALL) depends on the presence of risk factors including age, white blood cell count, immunophenotype and time to complete remission. In recent years, status of minimal residual disease (MRD) has been postulated as an additional risk criterion. This study prospectively evaluated the significance of MRD. Patients were treated with a uniform Polish Adult Leukemia Group (PALG) 4-2002 protocol. MRD status was assessed after induction and consolidation by multiparametric flow cytometry. Out of 132 patients included (age, 17-60 years), 116 patients were suitable for analysis. MRD level ‡0AE1% of bone marrow cells after induction was found to be a strong and independent predictor for relapse in the whole study population (P < 0AE0001), as well as in the standard risk (SR, P = 0AE0003) and high-risk (P = 0AE008) groups. The impact of MRD after consolidation on outcome was not significant. The combination of MRD status with conventional risk stratification system identified a subgroup of patients allocated to the SR group with MRD <0AE1% after induction who had a very low risk of relapse of 9% at 3 years as opposed to 71% in the remaining subjects (P = 0AE001). We conclude that MRD evaluation after induction should be considered with conventional risk criteria for treatment decisions in adult ALL.

TNF and its soluble receptors' plasma measurements represent valuable prognostic markers in lymphoma patients.