Fludarabine-Based Conditioning for Marrow Transplantation From Unrelated Donors in Severe Aplastic Anemia: Early Results of a Cyclophosphamide Dose De-Escalation Study Show Life-Threatening Adverse Events at Predefined Cyclophosphamide Dose Levels
07/2012
Journal Article
Authors:
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.
Secondary:
Biol Blood Marrow Transplant
Volume:
18
Pagination:
1007-1011
URL:
http://www.ncbi.nlm.nih.gov/pubmed/22546497
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.
