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

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34 Scopus citations

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/m2), and antithymocyte globulin was associated with excessive organ toxicity.

Original languageEnglish (US)
Pages (from-to)1007-1011
Number of pages5
JournalBiology of Blood and Marrow Transplantation
Volume18
Issue number7
DOIs
StatePublished - Jul 1 2012

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Keywords

  • Antithymocyte globulin
  • Bone marrow transplantation
  • Matched unrelated donor
  • Stem cell transplantation

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

Tolar, J., Deeg, H. J., Arai, S., Horwitz, M., Antin, J. H., McCarty, J. M., Adams, R. H., Ewell, M., Leifer, E. S., Gersten, I. D., Carter, S. L., Horowitz, M. M., Nakamura, R., Pulsipher, M. A., DiFronzo, N. L., Confer, D. L., Eapen, M., & Anderlini, P. (2012). 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. Biology of Blood and Marrow Transplantation, 18(7), 1007-1011. https://doi.org/10.1016/j.bbmt.2012.04.014