Bitan Menachem, Or Reuven, Shapira Michael Y, Resnick Igor B, Ackerstein Aliza, Samuel Simcha, Elad Sharon, Slavin Shimon
Department of Bone Marrow Transplantation & Cancer Immunotherapy, Hadassah-Hebrew University Medical Center Jerusalem 91120, Israel.
Haematologica. 2005 Aug;90(8):1089-95.
Busulfan is the most commonly used myeloablative alkylating agent, but is considered a poor anti-lymphocyte agent. Since engraftment of allogeneic stem cells depends not only on adequate immunosuppression but also on successful hematopoietic competition, and considering the fact that residual lymphocytes of host origin may play a beneficial role in preventing graft-versus-host disease (GVHD), we used low doses of oral busulfan as a single agent for conditioning prior to stem cell transplantation (SCT) in recipients of transplants from a variety of donors.
Fifteen heavily pretreated high-risk patients (age 25-66, median 42 years) with hematologic malignancies were conditioned with busulfan alone, 4mg/kg/day for 2, 3, or 4 consecutive days. No additional pre- or post-transplant immunosuppressive agents were used in order to exploit the capacity of donor lymphocytes to induce graft-versus-malignancy (GVM) effects.
Conditioning was well tolerated, trilineage engraftment was documented in all patients and none exhibited immune-mediated rejection. Time to recovery of absolute neutrophil count >0.5x10(9)/L and 1.0x10(9)/L was 12 - 38 (median 15) days and 12 - 41 (median 15) days, respectively. The time to platelet recovery >or=20 and >or=50x10(9)/L ranged from 0 to 26 (median 11) days, and from 0 to 83 (median 14) days, respectively. Acute GVHD (<or=grade I) occurred in 13/15 patients. Three patients benefited from long-term survival.
We suggest that using busulfan alone for the preparation of patients for SCT may be sufficient for engraftment, in very high-risk heavily pre-treated patients.
