Continuous Immuno-Chemotherapy Followed by High Dose and Autologous Cell Transplantation May Improve the Event-Free-Survival in Mantle Cell Lymphoma Patients. Experience at the European Institute of Oncology in Milan.

Mantle cell lymphoma (MCL) is an aggressive disease, currently incurable with standard-dose chemotherapy. Autologous cell transplantation (ASCT) is frequently considered a therapeutical approach in MCL, despite not generally being curative. In controlled studies upfront ASCT showed a significant event-free survival advantage, that might be improved by the addition of the anti-CD20 monoclonal-antibody (MoAb) (Rituximab®) in the myeloablative regimen. Based on these evidences, we prospectively analysed our patients (pts) affected by MCL, who received a continuous Rituximab administration in course on treatment. From May 2000 to the present we treated 22 pts with histological diagnosis of MCL, including 16 pts (73%) newly diagnosed. The majority were male (15/22) and the median age at diagnosis was 56 years old (range 35–66). Disease was stage III–IV: 21 pts with bone marrow involvement in 60%. Eleven pts presented extranodal involvement. The induction schedule included 2–4 CHOP-like regimen with MoAb (R-ACOD), followed by mobilization chemotherapy with cyclophosphamide, MoAb and G-CSF. Harvest was performed successfully in all pts with a median number of CD34-positive cells of 8.0 x 106/Kg (1.9–22.8 106/Kg). Subsequently the pts received 2 cycles of high-dose, cytarabine-based regimen with MoAb (R-ESHAP). Rituximab injections were given at standard dose (375 mg/mq). Before ASCT, 11 pts (50%) were in complete response (CR); in particularly 5 of them who were pretreated. Eight achieved partial response, while one was in progression. Two pts were not restaged. One patient did not undergo ASCT, because of serious pulmonary infection after high-dose cytarabine. In terms of conditioning regimen all pts received Rituximab (375 mg/mq), Melphalan (180mg/mq) in association with either Idarubicin (15mg/mq for 3 days) in 13 pts and or Novantrone (60 mg/mq for 1 day) in 8 pts. After stem cell reinfusion and G-CSF from Day +5, the median time to recovery (neutrophil counts >0.5x103) was 14 days (range 13–28 days) in the first regimen versus 10 days (range 8–11 days) in the more recent regimen. During aplasia the infection rate was low, as a matter of fact we observed just two episodes of pneumonia, that resolved at neutrophil recovery. No toxic death was reported. Response at 3 months after ASCT was evaluable in 19 patients (90%); one was lost at follow-up, while one has been transplanted one month ago. Seventy patients (80%) achieved complete response, maintained in 11 of them after a median time of 23 month (range 10–79) after ASCT; seven of them were in complete response before the transplant procedure. With a median time of 27 months (range 9–46 months) 7 patients progressed and 4 of these died because of lymphoma. Our study supports that ASCT can be considered a valid approach to induce high response rate. To enhance the ASCT outcomes, the addition of Rituximab can be considered a feasible approach associated with its “purging in vivo” effect. Long-term disease control might be reflected upon a plateau in the survival curve, but a randomised study and longer follow up is warranted.