Factors Determining Survival after Unrelated Donor Stem Cell Transplantation in Primary Refractory Acute Myeloid Leukemia

Allogeneic stem cell transplantation using an HLA identical sibling donor has the capacity to produce long term disease free survival in a significant number of patients with primary refractory acute myeloid leukaemia (AML). The increased availability of volunteer unrelated donors has resulted in allogeneic transplantation becoming a realistic option in large numbers of patients lacking a sibling donor. However the outcome of patients with primary refractory AML after unrelated donor transplantation has not been systematically examined before. We have therefore studied the outcome of 186 adults with primary refractory AML who underwent an unrelated donor transplant from 1995 to 2006. All patients were refractory to induction chemotherapy having received a mean of 2.2 courses of chemotherapy (range 1 to 6). Cytogenetic status at diagnosis is available in 96 patients: 3 patients had good risk cytogenetics, 60 intermediate risk and 33 adverse risk cytogenetics by MRC criteria. The median interval from diagnosis to transplant was 4.2 months (range 2–6 months). 141 patients underwent transplantation from a 6/6 matched unrelated donor and 45 from a mismatched unrelated donor. 150 patients were transplanted using GCSF mobilised peripheral blood stem cells. 136 patients were transplanted using a myeloablative conditioning (MAC) regimen. 50 patients were transplanted using a reduced intensity conditioning (RIC) regimen of whom 30 received a low dose TBI based regimen. 137 patients achieved a complete remission (CR) post-transplant. The 2 year overall survival for the whole group was 31% and 43% for patients who achieved a CR post-transplant. The day 100 non-relapse mortality was 16% (19% for MAC allografts v 9% for RIC allografts). In univariate analysis time to transplant (<4.2 months), presentation white blood cell count, the absence of circulating blasts at the time of transplant, and the use of a RIC regimen were associated with improved survival. Adverse risk cytogenetics at diagnosis was associated with a decreased OS. In multivariate analysis a short time from diagnosis to transplant (p=0.05), the absence of adverse risk cytogenetics (p=0.02) and the use of a RIC regimen (p=0.036) were associated with improved survival. The improved survival in patients receiving a reduced intensity transplant occurred despite their increased age at the time of transplant (54 years v 40 years). On the basis of this study we conclude that there is an important role for unrelated donor transplantation in primary refractory AML-particularly if performed early after diagnosis. The encouraging results obtained using a RIC require further examination.