Improved Outcome With T-Cell–Depleted Bone Marrow Transplantation for Acute Leukemia

Author:

Aversa Franco1,Terenzi Adelmo1,Carotti Alessandra1,Felicini Rita1,Jacucci Roberta1,Zei Tiziana1,Latini Paolo1,Aristei Cynthia1,Santucci Antonella1,Martelli Maria Paola1,Cunningham Isabel1,Reisner Yair1,Martelli Massimo F.1

Affiliation:

1. From the BMT Program, Section of Hematology and Clinical Immunology, University of Perugia, Perugia, Italy; and Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.

Abstract

PURPOSE: To eliminate the risk of rejection and lower the risk of relapse after T-cell–depleted bone marrow transplants in acute leukemia patients, we enhanced pretransplant immunosuppression and myeloablation. PATIENTS AND METHODS: Antithymocyte globulin and thiotepa were added to standard total-body irradiation/cyclophosphamide conditioning. Donor bone marrows were depleted ex vivo of T lymphocytes by soybean agglutination and E-rosetting. This approach was tested in 54 consecutive patients with acute leukemia who received transplants from HLA-identical sibling donors or, in two cases, from family donors mismatched at D-DR. No posttransplant immunosuppressive treatment was given as graft-versus-host disease (GVHD) prophylaxis. RESULTS: Neither graft rejection nor GVHD occurred. Transplant-related deaths occurred in six (16.6%) of 36 patients in remission and in seven (38.8%) of 18 patients in relapse at the time of transplantation. The probability of relapse was .12 (95% confidence interval [CI], 0 to .19) for patients with acute myeloid leukemia and .28 (95% CI, .05 to .51) for patients with acute lymphoblastic leukemia who received transplants at the first or second remission. At a median follow-up of 6.9 years (minimum follow-up, 4.9 years), event-free survival for patients who received transplants while in remission was .74 (95% CI, .54 to .93) for acute myeloid leukemia patients and .59 (95% CI, .35 to .82) for acute lymphoblastic leukemia patients. All surviving patients have 100% performance status. CONCLUSION: Adding antithymocyte globulin and thiotepa to the conditioning regimen prevents rejection of extensively T-cell–depleted bone marrow. Even in the complete absence of GVHD, the leukemia relapse rate is not higher than in unmanipulated transplants.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

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