Originally published as JCO Early Release 10.1200/JCO.2005.09.117 on March 7 2005

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Full Haplotype-Mismatched Hematopoietic Stem-Cell Transplantation: A Phase II Study in Patients With Acute Leukemia at High Risk of Relapse

From the Hematology and Clinical Immunology Section, Department of Clinical and Experimental Medicine, University of Perugia, Italy; the Department of Immunology, Weizmann Institute, Rehovot, Israel

Address reprint requests to Franco Aversa, MD, HSCT Unit, Hematology Section, University of Perugia, 06100 Perugia, Italy; e-mail: aversa{at}unipg.it

PURPOSE: Establishment of hematopoietic stem-cell (HSC) transplantation from mismatched relatives is feasible for patients with acute leukemia. As our original method of graft processing was unsuitable for large-scale clinical studies, we use automated devices for CD34+ cell purification.

PATIENTS AND METHODS: Sixty-seven patients with acute myeloid leukemia (AML; 19 complete remission [CR] 1, 14 CR 2, nine CR > 2, 25 in relapse) and 37 with acute lymphoid leukemia (ALL; 14 CR 1, eight CR 2, two CR > 2, 13 in relapse) were conditioned with total-body irradiation, thiotepa, fludarabine, and antithymocyte globulin. Peripheral-blood progenitor cells were mobilized with recombinant human granulocyte colony-stimulating factor and depleted of T-cells using CD34+ cell immunoselection. No post-transplantation graft-versus-host disease (GvHD) prophylaxis was administered.

RESULTS: Primary engraftment was achieved in 94 of 101 assessable patients. Six of the seven patients who rejected the primary graft, engrafted after a second transplantation. Overall, 100 of 101 patients engrafted. Acute GvHD developed in eight of 100 patients, and chronic GvHD, in five of 70 assessable patients. Thirty-eight patients died of nonleukemic causes. Relapse occurred in nine of 66 patients receiving transplantation in remission and in 17 of 38 receiving transplantation in relapse. Median follow-up of the 40 patients who survived event-free was 22 months (range, 1 to 65 months). Event-free survival (± standard deviation) rate was 48% ± 8% and 46% ± 10%, respectively, for the 42 AML and 24 ALL patients receiving transplantation in remission.

CONCLUSION: Our transplantation procedure provides reliable, reproducible CD34+ cell purification, high engraftment rates, and prevention of GvHD. The mismatched-related transplant emerges as a viable, alternative source of stem cells for acute leukemia patients without matched donors and/or those who urgently need transplantation.

Supported in part from AIRC (Italian Cancer Association), Perugia Section of the AIL (Italian Leukaemia Association), AULL (Umbrian Leukaemia and Lymphoma Association), the Daniele Chianelli Foundation and the Perugia Cassa di Risparmio Foundation.

Presented at the Tandem Meeting 2003, Keystone Symposia, Keystone, CO, January 30-Feb 3, 2003; 19th Meeting of the Belgian Hematological Society, Brussels, Belgium, January 30-31, 2004; 4th International Workshop on Haploidentical Transplants. Naples, Italy, July 8-10, 2004.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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