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Objectives: Treatment intensification (including consolidative high‐dose chemotherapy with autologous stem cell transplantation [HDT‐ASCT]) significantly improved outcome in primary central nervous system lymphoma (PCNSL) patients. Methods: We conducted a multicenter, retrospective analysis of newly diagnosed PCNSL patients, treated with intensified treatment regimens. The following scores were evaluated in terms of overall survival (OS) and progression‐free survival (PFS): Memorial Sloan‐Kettering Cancer Center (MSKCC), International Extranodal Lymphoma Study Group (IELSG), and three‐factor (3F) prognostic score. Further, all scores were comparatively investigated for model quality and concordance. Results: Altogether, 174 PCNSL patients were included. One hundred and five patients (60.3%) underwent HDT‐ASCT. Two‐year OS and 2‐year PFS for the entire population were 73.3% and 48.5%, respectively. The MSKCC (p =.003) and 3F score (p <.001), but not the IELSG score (p =.06), had the discriminatory power to identify different risk groups for OS. In regard to concordance, the 3F score (C‐index [0.71]) outperformed both the MSKCC (C‐index [0.64]) and IELSG (C‐index [0.53]) score. Moreover, the superiority of the 3F score was shown for PFS, successfully stratifying patients in three risk groups, which also resulted in the highest C‐index (0.66). Conclusion: The comparative analysis of established PCNSL risk scores affirm the clinical utility of the 3F score stratifying the widest prognostic spectrum among PCNSL patients treated with intensified treatment approaches. [ABSTRACT FROM AUTHOR]

Despite bendamustine-rituximab (BR) showed disappointing efficacy in diffuse large B cell lymphoma (DLBCL), it is still occasionally used as first-line treatment in older DLBCL patients instead of recommended R-CHOP. This multicentre, retrospective study was aimed to clarify circumstances in which BR may be justified in this setting. Patients ≥ 65 years with ECOG performance status (PS) ≥ 2 or ≥ 75 years regardless of PS were included. A total of 140 patients were analysed (BR, 68; R-CHOP, 72). BR patients were older (p < 0.001) and were diagnosed more often with high-risk disease (p = 0.03); no difference regarding comorbidities or PS was seen. Compared with R-CHOP, BR was associated with marked inferior overall survival (OS) (16.3 vs. 75.4 months; p = 0.006) and progression-free survival (PFS) (11.0 vs. 62.3 months; p < 0.001). In multivariate analysis, only high age-adjusted Charlson Comorbidity Index (aaCCI) was associated with inferior PFS in R-CHOP patients (hazard ratio 2.67; p = 0.012). Comparing the subgroup of BR and R-CHOP patients with high aaCCI, there was no difference in OS (p = 0.73) or PFS (p = 0.75). Due to the observed non-superiority of R-CHOP in older DLBCL patients with comorbidities, we propose that this subgroup may be treated alternatively with BR, whereas all other older patients are clearly R-CHOP candidates. [ABSTRACT FROM AUTHOR]

A total of 81 severe aplastic anaemia patients, aged 2–63 years, received human leucocyte antigen-matched related marrow grafts after cyclophosphamide + antithymocyte globulin followed by postgrafting methotrexate + ciclosporin. Median follow-up was 9·2 years. Ninety-six per cent of patients had sustained engraftment, 24% developed acute graft- versus-host disease (GVHD), grade II in all but two patients, and 26% developed chronic GVHD; all surviving patients eventually responded to immunosuppressive therapy. Six patients developed cancer: one fatal lymphoma and five carcinomas (all five patients are now free of cancer). Survival was 88%. The regimen appeared well tolerated and effective in heavily pretreated patients with aplastic anaemia. [ABSTRACT FROM AUTHOR]

The therapy of patients with relapsed or refractory indolent lymphoma relies on the development of new drug combinations. The drugs bendamustine and fludarabine have cytotoxic activity as monotherapy in indolent lymphoma and show synergism in vitro . In this study, we combined both drugs in a multicenter clinical phase I/II trial to evaluate their toxicity and efficacy. Bendamustine was given at 30 or 40 mg/m 2 /d (dose levels 1 and 2), fludarabine at 30 mg/m 2 /d, each drug on days 1 to 3. Six cycles were to be given every 4 weeks. A total of 29 patients with relapsed or refractory indolent lymphoma were included in the study. During phase I, 9 patients were treated at dose level 1 and 7 patients at dose level 2. Thirteen patients were added to the study during phase II. Fourteen patients had follicular lymphoma, 11 patients mantle cell lymphoma, 2 patients lymphoplasmocytic and 2 patients nodal marginal zone lymphoma. Median age was 62 years (range 39 - 74). All patients were in stages III or IV of their disease and had received prior chemotherapy with or without additional radio- or immunotherapy. The dose limiting toxicity was hematotoxicity in all cases and occurred in 3 of 7 evaluable patients at dose level I and in 3 of 7 patients at dose level 2. One patient at dose level 2 died of sepsis in neutropenia with persistent thrombocytopenia. The study was continued at dose level 1 (phase II). Analysis of 19 evaluable patients treated at dose level 1 reveiled hematotoxicity CTC grade III in 47% and grade IV in 26%. Neutropenic fever occurred in 4 patients (21%). On an intent-to-treat basis, 45% or 32% of all patients at dose level 1 reached CR or PR, respectively. Nine of 9 patients with mantle cell lymphoma responded to therapy. The overall response rate was 77%. Eight of 15 responders relapsed after a median follow-up time of 14 months (range 2 - 43). The major complication of fludarabine in combination with bendamustine is hematotoxicity. Dose level 1 with 30 mg/m 2 /d of both drugs on days 1 to 3 was defined as the recommended dose. Despite unfavorable prognostic features (histologic subtype, stage of disease, pretreatment) response rates were good with this regimen. [ABSTRACT FROM AUTHOR]