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.

Journal Article (Journal Article;Multicenter Study)

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.

Full Text

Duke Authors

Cited Authors

  • Tolar, J; Deeg, HJ; Arai, S; Horwitz, M; Antin, JH; McCarty, JM; Adams, RH; Ewell, M; Leifer, ES; Gersten, ID; Carter, SL; Horowitz, MM; Nakamura, R; Pulsipher, MA; Difronzo, NL; Confer, DL; Eapen, M; Anderlini, P

Published Date

  • July 2012

Published In

Volume / Issue

  • 18 / 7

Start / End Page

  • 1007 - 1011

PubMed ID

  • 22546497

Pubmed Central ID

  • PMC3677744

Electronic International Standard Serial Number (EISSN)

  • 1523-6536

Digital Object Identifier (DOI)

  • 10.1016/j.bbmt.2012.04.014


  • eng

Conference Location

  • United States