Rituximab/Chemotherapy Induction Treatment Followed by High-Dose Therapy and Autologous Transplantation in Patients with Mantle Cell Lymphoma.

Abstract

Between September 1998 and September 2003, 25 patients with Mantle Cell Lymphoma (MCL) were treated in our centres with a treatment combining rituximab + chemotherapy at induction with subsequent consolidation high-dose chemo/radiotherapy (HDT) and autologous PBSC-transplantation. Twenty-two (80%) patients received this treatment in first line therapy. Median age of patients was 53 (range: 41–65). All patients had a disseminated disease with a bone marrow (BM) involvement in 23 (92%) patients. Elevated LDH was present in 11 patients. All patients except one had a good performance status. IPI score was low in 5 patients, low-intermediate in 10 patients, high-intermediate in 7 patients and high in 3 patients. Chemotherapy induction regimens were: R-CHOP (n=7 pts), R-ACVB (n=4 pts), R-ESHAP (n=1 pts), R-DHAP (n=1pts), or sequential CHOP+DHAP/ESHAP+Rituximab (n=12pts) regimens. Rituximab was giving simultaneously with the chemotherapy in 13 patients or just before harvest in 12 patients. Number of rituximab injections was four in all patients except one that received 5 injections. PBSC harvest was done after cyclophosphamide or cyclophosphmide + etoposide followed by G-CSF and was successful in all patients with a median number of CD34+ cells at 6.44 106/kg. HDT included TBI in 21 patients.After induction therapy, all patients were in response: 16 (64%) reached a CR and 9 (36%) a PR because of persistence of a weak (<5%) BM involvement. Evaluation three months after transplant showed a CR in 17 (68%) patients and a PR in 7 (24%) patients because of weak BM involvement. At 3 years, 80% (20/25) of the patients are still alive (Figure). With a median follow-up at 4 years, median time to progression was 3.3 years. Four patients died from progressive disease. Transplantation toxicities were similar to those observed with regular induction treatment without rituximab with a median time of achievement of a PN count > 0.5GI/L at 10 days. One patient died before neutrophil recovery because of undocumented pulmonary infection. No patient presented late neutropenia. In conclusion, combined induction chemotherapy with rituximab followed by HDT dramatically improved the overall survival and the progression free survival in MCL patients, without adding hematological toxicities and infectious complications. [Display omitted]