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To retrospectively assess the efficacy of bendamustine alone and with rituximab (R-B), 109 patients with relapsed chronic lymphocytic leukaemia (CLL) were enrolled in 24 Italian centres. The median age was 66 years (range 39-85). Forty-three percent of patients had relapsed and 57% were resistant (median previous therapies = 3; range 1-8). Twenty-two patients received bendamustine alone and 87 patients received R-B (median B dosage: 100 mg/m per day, range 90-130 mg/m per day). The overall response rate was 69·6% (complete response 28·6%; partial response 41%), and was significantly higher in patients treated with R-B ( P = 0·014) and in those responsive to the previous treatment ( P = 0·04). After a median follow-up of 7·9 months (range 1-148), the median progression-free survival was 16 months and the median duration of response was 13 months. Median overall survival (OS) was 16·8 months for the whole cohort; patients not responding to the treatment had a significantly worse outcome than those who attained a response ( P = 0·0001). In multivariate analysis, only resistant disease status at start of bendamustine treatment (HR 3·2, 95% CI 1·4-7·3, P = 0·006) had an independent prognostic value for OS. Toxicity was manageable and mostly haematological. In conclusion, in our experience R-B was an effective and well-tolerated treatment for relapsed/refractory CLL patients, producing a remarkable high CR rate and mild toxicity. [ABSTRACT FROM AUTHOR]

The genomic profile of mantle cell lymphoma (MCL) has been reported to be significantly different from that of other indolent lymphoproliferative disorders, Topoisomerase IIα, glutathione-s-transferaseπ (GSTπ) and ABCG2 (BCRP) chemoresistance genes being over-expressed in MCL. In our study, expression levels of the above mentioned genes plus MDR1 were tested on bone marrow samples from 20 patients treated with Rituximab plus hyper-CVAD regimen, in order to evaluate a possible impact of the chemoresistance phenomenon on this promising treatment regimen. All patients expressed ABCG2 and MDR1 genes; 85% of cases expressed GSTπ and topoisomerase IIα. Only ABCG2 were over-expressed in comparison both with marrow from healthy donors and tonsilar CD5+/CD20+ lymphocytes (adopted as normal counterpart of the neoplastic population). The overall response rate of the entire series was 87.5%, with 44% of complete responses. Fifty-seven percent of patients achieved the clearance of minimal residual disease. Levels of tested genes did not condition either quality of clinical response or PFS (76% at 24 months). Nevertheless, an ABCG2 higher expression appeared associated with a worse PFS and levels of this gene paralleled the status of minimal residual disease. A further evaluation of ABCG2 expression in larger series of MCL patients would be suitable. [ABSTRACT FROM AUTHOR]

Abstract: Chronic myeloid leukemia (CML) and hairy cell leukemia (HCL) are two distinct haematological disorders. Only one single case of coexistence of the two pathologies at diagnoses has been previously reported. We present a second case of coexistence at diagnosis, indicating the diagnostic procedures involving morphological, immunophenotyping, and molecular testing. We decided to use Interferon as common first-line therapy and Imatinib and Rituximab (anti-CD20 monoclonal antibody), to improve the first-line therapy result, obtaining a complete molecular remission for CML and clinical remission with molecular minimal residual disease for HCL. After a critical analysis of the results, we speculate on the different clonal origin of the two pathologies. [Copyright &y& Elsevier]

Cervetti G, Galimberti S, Andreazzoli F, Fazzi R, Cecconi N, Caracciolo F, Petrini M. Rituximab as treatment for minimal residual disease in hairy cell leukaemia. Eur J Haematol 2004: 73: 412–417.© Blackwell Munksgaard 2004.Purine analogues have dramatically improved the outcome of patients affected by hairy cell leukemia (HCL), although complete eradication of disease was achieved in few cases. The purpose of this study was to evaluate the role of Rituximab in eradicating minimal residual disease (MRD) in HCL patients after a pre-treatment with 2-chloro-deoxy-adenosine (2-CdA). Ten patients received four cycles of Rituximab after administration of Cladribrine. Before starting anti-CD20 antibody, two patients were in complete remission, six in partial remission and two showed no significant response to Cladribrine. All cases resulted IgH-positive. Median time from the last 2-CdA infusion was 5.7 months. Eight of 10 patients [four in partial remission (PR), two in complete remission (CR) and two unresponsive after 2-CdA] were evaluable for response. Two months after the end of anti-CD20 therapy, all evaluated patients presented a complete haematological remission. Moreover, Rituximab increased percentage of molecular remission up to 100% 1 yr after the end of treatment. Interestingly, in all cases but one, including those persistently polymerase chain reaction (PCR)-positive, semi-quantitative molecular analyses showed MRD levels lower than those found before Rituximab administration. Toxicity was very mild. The present results not only confirm the therapeutic effect of Rituximab, but also show its relevance in eradicating MRD in HCL. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented about the use of Rituximab as treatment for minimal residual disease in hairy cell leukemia.