A Retrospective Analysis of Mantle Cell Lymphoma Patients Series Treated Upfront by Sequential High Dose Immunochemotherapy Supported by In Vivo Purged Stem Celle Double Autologous Transplantation: A Monocentric Experience

Abstract 4949

Mantle Cell Lymphoma (MCL) is a rare lymphoma that accounts for 3–10% of all non Hodgkin's Lymphoma in adults. Being associated with rapid progression and high recurrence rate, although some treatment improvements during the last years, it is still considered an incurable disease. In order to overcome the poor outcome obtained with conventional chemotherapy, new treatment strategies using high dose chemotherapy supported by autologous stem cell transplantation (ASCT) have been developed in young patients. In particular the use of high dose cytarabine and rituximab prior to ASCT has been demonstrated to improve outcome in terms of response and disease free survival. The present study is a restrospective analysis conducted in our centre in order to evaluate the outcome of 16 MCL patients treated upfront with sequential high dose immunochemotherapy followed by double ASCT.

From 2000 to 2011, 16 MCL patients, eligible for ASCT, have been consecutively treated as follow: a) standard dose phase: APO: doxorubicin, 75 mg/sqm i.v., day 1; prednisone, 60 mg/sqm orally, day 1 to 5 and day 9 to 12; vincristine, 1.4 mg/sqm i.v., day 1 and 8; DHAP: cisplatin 70 mg/sqm, day 1; cytarabin 1500 mg/sqm i.v., days 2–3; dexametasone 40 mg i.v., days 1 to 3; b) rituximab high dose sequence: high dose cyclophosphamide (CTX 5 g/sqm) and high dose cytarabine (Ara-C 2 g/sqm every 12 hours for 6 consecutive days) followed by peripheral blood stem cell (PBSCs) collection; c) high dose melphalan (180 mg/sqm) and high dose mitoxantrone plus melphalan (60 mg/sqm and 180 mg/sqm, respectively) followed by PBSCs infusion. Rituximab (375 mg/sqm) was infused twice after CTX, cytarabine and double autologous transplantation (modified from Gianni et al, Blood, 102, 749, 2003). All patients (9 female and 7 male) had a histological diagnosis of MCL according to the WHO classification criteria; molecular rearrangement of bcl-1 locus was detected by PCR in the bone marrow of 8 patients. The median age at diagnosis was 57 years (range 50–68); 14 patients were in stage IV and 2 in stage III; 2 patients had bulky disease at presentation. Four patients were in overt leukemic phase and 2 had extranodal localization. According to MIPI score, 14 patients (87%) were classified as low risk and 2 (13%) as intermediate risk. Double transplant was performed in all patients except one (who refused it). The standard dose phase, including a median number of 4 cycles (range 3–5), was generally well tolerated, with only one patient experiencing tumor lysis syndrome. After induction, clinical CR was achieved in six patients. PBSCs were successfully collected after both the CTX/rituximab (1.8-9.7×10̂6/Kg) and the Ara-C/rituximab (7.1- 40.0×10̂6/Kg) cycles. At the end of these phases, 7 patients (44%) were in CR while 9 (56%) were in PR. Following transplants, median times to ANC >500/μL were 11 days (range 10–14) in both the procedures, whereas median times to platelet recovery (>50000/μL) were 19 days (range 10–44) after the first transplant and 24 days (range 11–298) after the second one. After a median follow-up of 38 months (range 14–111), 10 patients (62%) were alive (8 in CR, 2 in relapse), whereas 6 died from disease progression.

Our study confirmed that in MCL the use of sequential high dose immunochemotherapy including rituximab and high dose cytarabine followed by double autologous transplantation is associated to high remission rates with long-term disease-free survival in a significant proportion of patients.