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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


Journal Article

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.

Biol Blood Marrow Transplant




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.

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