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.
Bibliographical noteFunding Information:
We thank Juan Wu and Yanli Wang for help with manuscript preparation, Erica Sanchez for secretarial assistance, and the clinical investigators who entered and managed the patients in this study. The BMT CTN is supported in part by Grant EQ1 U10HL069294 from the National Heart, Lung, and Blood Institute and the National Cancer Institute .
- Antithymocyte globulin
- Bone marrow transplantation
- Matched unrelated donor
- Stem cell transplantation