Treatment of advanced acute leukaemia with allogeneic bone marrow transplantation from unrelated donors

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Abstract
Bone marrow transplantation from a histocompatible sibling donor may produce complete remission in patients with induction failure or relapsed acute leukaemia. Through the National Marrow Donor Program, histocompatible bone marrow from unrelated donors has become available for high-risk patients. In this study we analyse the results of matched unrelated bone marrow transplant in 55 patients with highly advanced acute myelogenous and acute lymphoblastic leukaemia. 28 patients with advanced acute lymphoblastic leukaemia and 27 patients with advanced acute myelogenous leukaemia, age 2-51, were treated with high-dose chemoradiotherapy and transplantation of 6/6 HLA matched (n = 46) or one antigen mismatched (n = 9) unrelated donor bone marrow. After a median follow-up of 36 months, 13 patients remain alive 17-74 months after transplant for a 2-year actuarial disease-free and overall survival of 23 +/- 12% (median disease-free survival 3.5 months). The actuarial risk of relapse is 24 +/- 16% at 1 year. Moderate to severe graft-versus-host disease occurred in 27/47 evaluable patients (57%). Significant prognostic factors for poor leukaemia-free survival include age > 21, abnormal karyotype, and active leukaemia at the time of transplant. Other pretreatment characteristics such as gender or type of leukaemia were not significant prognostic factors. Our results show that matched unrelated bone marrow transplant for patients with advanced acute leukaemia may provide long-term leukaemia-free survival, but transplant-related complications produce a significant impact on survival with older age and adverse disease characteristics predicting for poor prognosis.