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Early Autologous Stem-Cell Transplantation Versus Conventional Chemotherapy as Front-Line Therapy in High-Risk, Aggressive Non-Hodgkin’s Lymphoma: An Italian Multicenter Randomized Trial

Maurizio Martelli, Filippo Gherlinzoni, Amalia De Renzo, Pier Luigi Zinzani, Antonio De Vivo, Maria Cantonetti, Brunangelo Falini, Sergio Storti, Giovanna Meloni, Manuela Rizzo, Anna Lia Molinari, Francesco Lauria, Luciano Moretti, Vito Michele Lauta, Patrizio Mazza, Luciano Guardigni, E. Pescarmona, S.A. Pileri, Franco Mandelli, Sante Tura

From the Departments of Cellular Biotechnology and Hematology and Experimental Medicine and Pathology, University "La Sapienza" of Rome, Hematology University "Tor Vergata" Rome, and Division of Hematology "La Cattolica" University of Rome, Rome; Institute of Hematology and Medical Oncology, University of Bologna, Bologna; Division of Hematology, University of Napoli, Napoli; Hematology University of Perugia, Perugia; Division of Hematology, Ravenna Hospital, Ravenna; Division of Hematology, Pesaro Hospital, Pesaro; Division of Internal Medicine, University of Bari, Bari; Division of Hematology, Taranto Hospital, Taranto; and Division of Hematology, Cesena Hospital, Cesena; Italy.

Address reprint requests to Maurizio Martelli, MD, Dipartimento Biotecnologie Cellulari ed Ematologia, University "La Sapienza" via Benevento, 6 00161 Roma, Italy; email: martelli{at}bce.med.uniroma1.it.

Purpose: To evaluate the role of early intensification with high-dose therapy (HDT) and autologous stem-cell transplantation (ASCT) as front-line chemotherapy for patients with high-risk, histologically aggressive non-Hodgkin’s lymphoma (NHL).

Patients and Methods: We planned a multicenter, randomized trial to compare a conventional chemotherapy regimen of methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B; arm A) with an abbreviated regimen of MACOP-B (8 weeks) followed by HDT and ASCT (arm B) for intermediate-high-risk/high-risk patients (according to the age-adjusted International Prognostic Index). From September 1994 to April 1998, 150 patients with aggressive lymphoma were enrolled onto the trial. Seventy-five patients were randomly assigned to arm A and 75 patients were randomly assigned to arm B. In both arms, involved-field radiation therapy (36 Gy) was delivered to the site of bulky disease.

Results: The rate of complete response was 68% in arm A and 76% in arm B (P = not significant [NS]). Three toxic deaths (4%) occurred in arm B and one (1%) occurred in arm A (P = NS). In arm B, 30 patients (40%) did not undergo HDT and ASCT. According to the intention-to-treat analysis at a median follow-up of 24 months, 5-year overall survival probability in arms A and B was 65% and 64% (P = .95), 5-year progression-free survival was 49% and 61% (P = .21), and 5-year relapse-free survival was 65% and 77% (P = .22), respectively.

Conclusion: Abbreviated chemotherapy followed by intensification with HDT-ASCT is not superior to conventional chemotherapy in patients with high-risk, aggressive NHL. Additional randomized trials will clarify whether HDT-ASCT as front-line therapy after a complete course of conventional chemotherapy improves survival in this group of patients.

Supported by Ministero dell’ Università e Ricerca Scientifica (MURST) 40%.

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