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.

Publication Type
Journal Article
Year of Publication
Tolar, Jakub; Deeg, H Joachim; Arai, Sally; Horwitz, Mitchell; Antin, Joseph H; McCarty, John M; Adams, Roberta H; Ewell, Marian; Leifer, Eric S; Gersten, Iris D; Carter, Shelly L; Horowitz, Mary M; Nakamura, Ryotaro; Pulsipher, Michael A; Difronzo, Nancy L; Confer, Dennis L; Eapen, Mary; Anderlini, Paolo
Biol Blood Marrow Transplant
Date Published
2012 Jul
Acute Disease; Adolescent; Adult; Aged; Anemia, Aplastic; Antilymphocyte Serum; Antineoplastic Agents; Bone Marrow Transplantation; Child; Cyclophosphamide; Drug Administration Schedule; Drug Dosage Calculations; Female; Humans; Male; Middle Aged; Survival Rate; Transplantation Conditioning; Unrelated Donors; Vidarabine; Whole-Body Irradiation

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.