Unrelated donor hematopoietic cell transplantation (HCT) as treatment for acute myeloid leukemia (AML) in first remission

Abstract

7000 Background: Unrelated donor HCT has been used with increasing frequency for the treatment of AML patients in first remission. Methods: Between 1990 and 2005, 105 adult patients with AML [66 (62%) primary and 39 (38%) secondary] received T- cell-replete HCT from unrelated donors in Seattle. Results: Median age was 44 (range, 18–74) years. Seventy-nine patients received ablative conditioning for HCT (57% conditioned with cyclophosphamide plus total body irradiation (TBI), 43% with chemotherapy alone). Non- myeloablative doses of fludarabine (FLU; 25 mg/m2 daily for 3 days) and TBI (200 cGy) were delivered to 26 patients. Ninety-six percent of patients who underwent reduced-intensity conditioning received unrelated peripheral blood stem cells (PBSC) while 59% of myeloablative HCT patients received PBSC as their source of stem cells. For all patients, the leukemia-free survival (LFS) and non-relapse mortality estimated at 2 years were 53%, and 26%, respectively, as 27 patients died of transplant-related causes (pulmonary-6, cardiac-1, graft versus host disease (GVHD)-6, infection-5, and unknown-9). Twenty-two patients (21%) relapsed 2 to 83 months (median 5) post-transplant, and 56 patients are surviving disease-free 1 to 168 months (median 27) post-transplant. For 90 patients (86%) with intermediate-risk cytogenetics, 51 (57%) are surviving disease-free, with 16 (18%) relapsing. Fourteen patients (13%) were considered high risk based on unfavorable cytogenetics; 4 of these 14 (29%) are surviving disease-free and 6 (43%) have relapsed. The probability of grade 3/4 acute GVHD was 19% while the probability of clinical extensive chronic GVHD was 54% one year after transplant. Unfavorable cytogenetics (HR=2.16, p=.08), secondary leukemia (HR=1.71, p=.10), higher co-morbidity score (p<.0001), and HLA mismatching (HR=2.35, p=.02) were associated with an increased hazard of mortality. After controlling for these factors, non-ablative conditioning was not statistically worse than ablative conditioning (HR=1.21, p=.61). Conclusions: These data suggest that HCT using unrelated allografts has the potential to provide significant LFS for patients undergoing HCT for AML in first remission when an HLA family match is not available. No significant financial relationships to disclose.