Clearing of cells bearing the bcl-2 [t(14;18)] translocation from blood and marrow of patients treated with rituximab alone or in combination with CHOP chemotherapy

Purpose: Patients who were PCR-positive for B-cell leukemia-lymphoma 2 (bel-2) gene rearrangement [t(14;18)] were evaluated for responses to rituximab alone or combined with CHOP. Patients and methods: Patients had relapsed or refractory low-grade or follicular non-Hodgkin's lymphoma (IWF: A-D). The single-agent trial used 375 mg/m² weekly x 4; combination therapy included six cycles of CHOP and six 375 mg/m² infusions of rituximab. Bcl-2 analyses of bone marrow (BM) and peripheral blood (PB) samples at base-line and following therapy were performed using a PCR assay. Results: In the single-agent trial, of 70 patients whose peripheral blood (PB) was bcl-2 positive at baseline, 36 became bcl-2-negative, 13 remained positive, and 21 varied between positive and negative. The overall response rates (ORRs) were 72%, 31%, and 57%, respectively. Twelve of twenty-two patients with repeat bone marrow (BM) samples were bcl-2-negative three months post-treatment. Of 18 patients in the combination trial, 8 were bcl-2 positive in PB and/or BM. All of seven patients positive in PB at baseline and six of seven patients positive in BM were negative at the end of therapy; all patients responded to treatment (100% ORR). Conclusions: Rituximab, alone or combined with CHOP, eradicated bcl-2 positive cells from PB and BM in over half of the patients treated and was associated with a high overall clinical response rate. The impact on disease-free and overall survival awaits long-term follow up.