Non-myeloablative conditioning with allogeneic hematopoietic cell transplantation for the treatment of high-risk acute lymphoblastic leukemia |
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Authors: | Ram Ron Storb Rainer Sandmaier Brenda M Maloney David G Woolfrey Ann Flowers Mary E D Maris Michael B Laport Ginna G Chauncey Thomas R Lange Thoralf Langston Amelia A Storer Barry Georges George E |
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Affiliation: | 1Fred Hutchinson Cancer Research Center, Seattle, WA, USA;2University of Washington School of Medicine, Seattle, WA, USA;3Rocky Mountain Cancer Center, Denver, CO, USA;4Stanford University, Stanford, CA, USA;5Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA;6University of Leipzig, Leipzig, Germany;7Emory University, Atlanta, GA, USA |
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Abstract: | BackgroundAllogeneic hematopoietic cell transplantation is a potentially curative treatment for patients with acute lymphoblastic leukemia. However, the majority of older adults with acute lymphoblastic leukemia are not candidates for myeloablative conditioning regimens. A non-myeloablative preparative regimen is a reasonable treatment option for this group. We sought to determine the outcome of non-myeloablative conditioning and allogeneic transplantation in patients with high-risk acute lymphoblastic leukemia.Design and MethodsFifty-one patients (median age 56 years) underwent allogeneic hematopoietic cell transplantation from sibling or unrelated donors after fludarabine and 2 Gray total body irradiation. Twenty-five patients had Philadelphia chromosome-positive acute lymphoblastic leukemia. Eighteen of these patients received post-grafting imatinib.ResultsWith a median follow-up of 43 months, the 3-year overall survival was 34%. The 3-year relapse/progression and non-relapse mortality rates were 40% and 28%, respectively. The cumulative incidences of grades II and III-IV acute graft-versus-host disease were 53% and 6%, respectively. The cumulative incidence of chronic graft-versus-host disease was 44%. Hematopoietic cell transplantation in first complete remission and post-grafting imatinib were associated with improved survival (P=0.005 and P=0.03, respectively). Three-year overall survival rates for patients with Philadelphia-negative acute lymphoblastic leukemia in first remission and beyond first remission were 52% and 8%, respectively. For patients with Philadelphia chromosome-positive acute lymphoblastic leukemia in first remission who received post-grafting imatinib, the 3-year overall survival rate was 62%; for the subgroup without evidence of minimal residual disease at transplantation, the overall survival was 73%.ConclusionsFor patients with high-risk acute lymphoblastic leukemia in first complete remission, non-myeloablative conditioning and allogeneic hematopoietic cell transplantation, with post-grafting imatinib for Philadelphia chromosome-positive disease, can result in favorable long-term survival. (Clinicaltrials.gov identifier: NCT0036738) |
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Keywords: | acute lymphoblastic leukemia Philadelphia chromosome-positive allogeneic hematopoietic cell transplantation non-myeloablative conditioning imatinib |
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