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

Issa F. Khouri, Jorge Romaguera, Hagop Kantarjian, J. Lynn Palmer, William C. Pugh, Martin Korbling, Fredrick Hagemeister, Barry Samuels, Alma Rodriguez, Sergio Giralt, Anas Younes, Donna Przepiorka, David Claxton, Fernando Cabanillas, Richard Champlin

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335 Scopus citations


Purpose: Diffuse and nodular forms of mantle-cell lymphoma (MCL) are consistently 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/m2 administered with doxorubicin (DOX), vincristine (VCR), and dexamethasone (Hyper-CVAD) that alternated with high-dose methotrexate (MTX) and cytarabine (Ara-C). After four courses, patients were consolidated with high-dose CY, total-body irradiation, and autologous or allogeneic blood or marrow stem-cell transplantation. Patients and Methods: Forty-five patients were enrolled; 25 patients were previously untreated, 43 patients had Ann Arbor stage IV disease, and 42 patients 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 response [CR], 38%; partial response [PR], 55.5%) after four cycles of pretransplantation induction chemotherapy. All patients who went on to undergo transplantation achieved CRs. For the 25 previously untreated patients, the overall survival (os) and event-free survival (EFS) rates at 3 years were 92% (95% confidence interval [Cl], 80 to 100) and 72% (95% Cl, 45 to 98) compared with 25% (95% Cl, 12 to 62; P = .005) and 17% (95% Cl, 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 EF5 rate of 72% versus 28% (P = .0001) and a better OS rate (92% v 56%; P = .05). Treatment-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 transplantation is a promising new therapy for previously untreated patients with MCL.

Original languageEnglish (US)
Pages (from-to)3803-3809
Number of pages7
JournalJournal of Clinical Oncology
Issue number12
StatePublished - Dec 1998

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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