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

Jul-12

Journal Article

Authors:

Secondary:
Biol Blood Marrow Transplant

Volume:
18

Pagination:
1007-1011

URL:
http://www.ncbi.nlm.nih.gov/pubmed/22546497

Abstract:
<p>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.</p>