Fludarabine-based conditioning for marrow transplantation from unrelated donors in severe aplastic anemia: early results of a cyclophosphamide dose deescalation study show life-threatening adverse events at predefined cyclophosphamide dose levels
Jakub Tolar, H Joachim Deeg, Sally Arai, Mitchell Horwitz, Joseph H Antin, John M McCarty, Roberta H Adams, Marian Ewell, Eric S Leifer, Iris D Gersten, Shelly L Carter, Mary M Horowitz, Ryotaro Nakamura, Michael A Pulsipher, Nancy L Difronzo, Dennis L Confer, Mary Eapen, Paolo Anderlini, Jakub Tolar, H Joachim Deeg, Sally Arai, Mitchell Horwitz, Joseph H Antin, John M McCarty, Roberta H Adams, Marian Ewell, Eric S Leifer, Iris D Gersten, Shelly L Carter, Mary M Horowitz, Ryotaro Nakamura, Michael A Pulsipher, Nancy L Difronzo, Dennis L Confer, Mary Eapen, Paolo Anderlini
Abstract
Excessive adverse events were encountered in a Phase I/II study of cyclophosphamide (CY) dose deescalation in a fludarabine-based conditioning regimen for bone marrow transplantation from unrelated donors in patients with severe aplastic anemia. All patients received fixed doses of antithymocyte globulin, fludarabine, and low-dose total body irradiation. The starting CY dose was 150 mg/kg, with deescalation to 100 mg/kg, 50 mg/kg, or 0 mg/kg. CY dose level 0 mg/kg was closed due to graft failure in 3 of 3 patients. CY dose level 150 mg/kg was closed due to excessive organ toxicity (n = 6) or viral pneumonia (n = 1), resulting in the death of 7 of 14 patients. CY dose levels 50 and 100 mg/kg remain open. Thus, CY at doses of 150 mg/kg in combination with total body irradiation (2 Gy), fludarabine (120 mg/m(2)), and antithymocyte globulin was associated with excessive organ toxicity.
Copyright © 2012 American Society for Blood and Marrow Transplantation. All rights reserved.
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Source: PubMed