Chemoimmunotherapy with BR is effective and safe in patients with relapsed CLL and has notable activity in fludarabine-refractory disease. Major but tolerable toxicities were myelosuppression and infections. These promising results encouraged us to initiate a further phase II trial evaluating the BR regimen in patients with previously untreated CLL.

Key Points• Prognostic tool for CLL patients with high discriminatory power compared with conventional clinical staging systems.• Prognostication on the individual patient level independent of clinical stage.In addition to clinical staging, a number of biomarkers predicting overall survival (OS) have been identified in chronic lymphocytic leukemia (CLL). The multiplicity of markers, limited information on their independent prognostic value, and a lack of understanding of how to interpret discordant markers are major barriers to use in routine clinical practice.We therefore performed an analysis of 23 prognostic markers based on prospectively collected data from 1948 CLL patients participating in phase 3 trials of the German CLL Study Group to develop a comprehensive prognostic index. A multivariable Cox regression model identified 8 independent predictors of OS: sex, age, ECOG status, del(17p), del(11q), IGHV mutation status, serum b 2 -microglobulin, and serum thymidine kinase. Using a weighted grading system, a prognostic index was derived that separated 4 risk categories with 5-year OS ranging from 18.7% to 95.2% and having a C-statistic of 0.75. The index stratified OS within all analyzed subgroups, including all Rai/Binet stages. The validity of the index was externally confirmed in a series of 676 newly diagnosed CLL patients from Mayo Clinic. Using this multistep process including external validation, we developed a comprehensive prognostic index with high discriminatory power and prognostic significance on the individual patient level. The studies were registered as follows: CLL1 trial (NCT00262782, http:// clinicaltrials.gov), CLL4 trial (ISRCTN 75653261, http://www.controlled-trials.com), and CLL8 trial (NCT00281918, http://clinicaltrials. gov). (Blood. 2014;124(1):49-62)

The chimeric anti-CD20 monoclonal antibody rituximab has become part of the standard therapy for patients with non-Hodgkin's lymphoma (NHL). To date, more than 300 000 patients have been treated with rituximab worldwide, including patients with indolent and aggressive NHL, Hodgkin's disease and other B-cell malignancies. Combination of rituximab with cytotoxic agents or cytokines has been explored in a number of different studies. Rituximab is now also approved for patients with diffuse large B-cell lymphoma when combined with standard CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisone). The monoclonal antibody is generally well tolerated. Most adverse events are infusion-associated, including chills, fever and rigor related to the release of cytokines.

The results show that the training program is feasible and seems to have positive influences on physical performance and quality of life in patients undergoing an allogeneic HSCT. However, further studies are necessary to confirm these results.

The new FluCam regimen is effective and feasible in patients with relapsed and refractory B-CLL.