Hyper-CVAD and high-dose methotrexate/cytarabine followed by stem-cell transplantation: An active regimen for aggressive mantle-cell lymphoma

Purpose: Diffuse and nodular forms of mantle-cell lymphoma (MCL) are consis tently associated with poor prognosis. In an effort to improve the outcome, we adopted a treatment plan that consisted of four courses of fractionated cyclophosphamide (CY) 1,800 mg/m(2) administered with doxorubicin (DOX), v incristine (VCR), and dexamethasone (Hyper-CVAD) that alternated with high- dose methotrexate (MTX) and cytarabine (Ara-C). After four courses, patient s were consolidated with high-dose CY,total-body irradiation, and autologou s or allogeneic blood or marrow stem-cell transplantation. Patients and Methods: Forty-five patients were enrolled; 25 patients were p reviously untreated, 43 patients had Ann Arbor stage IV disease, and 42 pat ients had marrow involvement. Forty-one patients had diffuse histology, two patients had nodular, and two patients had blastic variants. Results: Hyper-CVAD/MTX-Ara-C induced a response rate of 93.5% (complete re sponse [CR], 38%; partial response [PR], 55.5%) after four cycles of pretra nsplantation induction chemotherapy. All patients who went on to undergo tr ansplantation achieved CRs. For the 25 previously untreated patients, the o verall survival (OS) and event-free survival (EFS) rates at 3 years were 92 % (95% confidence interval [CI], 80 to 100) and 72% (95% CI, 45 to 98) comp ared with 25% (95% CI, 12 to 62; P = .005) and 17% (95% CI, 10 to 43; P = . 007), respectively, for the previously treated patients. When compared with a historic control group who received a CY, DOX, VCR, and prednisone (CHOP )-like regimen, untreated patients in the study had a 3-year EFS rate of 72 % versus 28% (P = .0001) and a better OS rate (92% v 56%; P = .05). Treatme nt-related death occurred in five patients: all were previously treated and two received allogeneic transplants. Conclusion: The Hyper-CVAD/MTX-Ara-C program followed by stem-cell transpla ntation is a promising new therapy for previously untreated patients with M CL. (C) 1998 by American Society of Clinical Oncology.