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Bendamustine (Benda) has been recently approved in Japan. Not only Benda itself has the favorable toxicity profile, but also Benda in combination with Rituximab (R) seems to be superior because of synergy of the two drugs. We retrospectively analyzed the results of the treatment consisting of Benda with R (BR) for the patients with relapsed or refractory low-grade B cell lymphoma.

Patients and methods

Nineteen relapsed or refractory patients with follicular lymphoma [FL] (n = 11; 2 of which have transformed to diffuse large B cell lymphoma), mantle cell lymphoma [MCL] (n = 5), marginal zone lymphoma [MZL] (n = 1), lympho-plasmacytic lymphoma [LPL] (n = 1), small lymphocytic lymphoma [SLL] (n = 1), received BR therapy (at most six cycles of Benda [120:90:60 mg/m2 = 5:11:3 patients] on days 1–2 with or without dexamethasone every 21–35 days). The best response, adverse events and immunological parameters after therapy were evaluated.


The median age was 66 (52–84) years, and number of previous therapy was 1–7 (M = 2) regimen, that included R (19), Zevalin (7) and nucleoside analogues (4), respectively. The evaluable overall response rate was 89% (16/18; FL 9, MCL 4, MZL 1, LPL 1, SLL 1) with 28% (5/18; FL 2, MCL 2, MZL 1) complete response. Hematological toxic effects were prominent but manageable, including grade 3/4 neutropenia, anemia and thrombocytopenia which were demonstrated in 58%, 11%, 16% of the patients, respectively. Non-hematological grade 3/4 toxic effects were observed, such as pneumonia, empyema and hiccup in one patient, respectively, and vasculitis in three patients. Majority of the evaluable patients revealed a considerable reduction of peripheral CD4+ T-lymphocyte number and immunoglobulin level, and two patients showed cytomegalo-virus antigenemia, at various time points after therapy.


The results of our study suggest that BR therapy may play a promising role as a salvage therapy for low-grade B-cell lymphoma, not only for FL, but also for other types such as MCL, MZL, LPL and SLL. This therapy was well tolerated even in patients who had previously received radio-immunotherapy (Zevalin) or nucleoside analogues. Appropriate anti-infectious precautions seem to be necessary because of substantial immune-suppression.

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