Treatment of mantle-cell lymphomas with the VAD +/- chlorambucil regimen with or without subsequent high-dose therapy and peripheral blood stem-cell transplantation.

BACKGROUND: MCL is a well-described clinicobiological entity that presents the worst prognosis of the small-cell lymphomas. No treatment is known as the reference treatment. On the basis, first, of clinicobiological similarities between MCLs and multiple myelomas and, second, of our experience of chlorambucil in high intermittent dose in MCLs, we have treated MCL with the VAD regimen both with and without chlorambucil. PATIENTS AND METHODS: Thirty disseminated MCL patients from three institutions, most in relapse (70%), were treated with the classical VAD regimen: 4 weeks VAD for 12 patients and VAD with 12 mg chlorambucil (d20-d29) for 5 weeks (VAD+C) for 18 patients. Five patients received complementary high-dose therapy (Alkeran or cyclophosphamide HD with TBI) and peripheral blood stem-cell transplantation.
RESULTS: Complete response was achieved in 43% of the patients in which 84.5% were treated by VAD+C. The median overall survival from the diagnosis was 52 months, and from the first VAD +/- C (OSvad) was 22.5 months, with a 20.5 month (0-75) median follow-up between diagnosis and the first VAD +/- C. The OSvad was significantly better for patients with fewer than two prognostic factors (ECOG, lymphocytosis, blastic variant, LDH level, and Ki-67 score). Four of five patients treated with HDT and PBSCT were alive in CR 12.5 months (7-22) after the first VAD +/- C regimen.
CONCLUSION: The VAD regimen appears effective in disseminated MCL patients and even better when associated with chlorambucil. HDT and PBSCT appear promising in younger patients in CR before HDT. A multicenter prospective study is in preparation to confirm these encouraging results.