Successful engraftment with fludarabine, cyclophosphamide, and thymoglobulin conditioning regimen in unrelated transplantation for severe aplastic anemia: A phase II prospective multicenter study.

Antithymocyte globulin (ATG) has been used in severe aplastic anemia (SAA) as part of the conditioning regimen. Among the many kinds of ATG preparations, thymoglobulin had been found to be more effective for preventing graft-versus-host disease (GVHD) and the rejection of organ transplants. After the promising results of our preliminary study, we conducted a phase II prospective multicenter clinical trial using a fludarabine (Flu), cyclophosphamide (Cy), and thymoglobulin conditioning regimen to allow good engraftment in patients who underwent unrelated transplantation for SAA. Twenty-eight patients underwent bone marrow (N = 15) or mobilized peripheral blood (N = 13) transplantation from HLA-matched unrelated donors with Cy (50 mg/kg once daily intravenously (i.v.) on days -9, -8, -7, and -6), Flu (30 mg/m² once daily i.v. on days -5, -4, -3, and -2), and thymoglobulin (2.5 mg/kg once daily i.v. on days -3, -2, and -1). Donor-type hematologic recovery was achieved in all patients. The estimated survival rate (SR) was 67.9%, and all the events were treatment-related mortality (TRM), which included thrombotic microangiopathy (N = 2), pneumonia (N = 1), myocardiac infarction (N = 1), posttransplantation lymphoprolifarative disease (N = 3), and chronic GVHD-associated complications (N = 2). The SR of patients who received bone marrow (60.0%) was not different from that of patients who received mobilized peripheral blood (76.9%) (P = .351), but the SR of patients who received more than 15 units of red blood cells before transplantation (45.5%) was significantly lower than that of the other patients (82.4%) (P = .048). The Flu, Cy, and thymoglobulin conditioning regimen achieved promising results for successful engraftment, but the TRM was high. This study was registered at www.clinicaltrials.gov (NCT00737685), and now we are performing a new multicenter study (NCT00882323) to decrease the TRM by reducing the dose of Cy.