Comparable Outcome after Allogeneic Hematopoietic Cell Transplantation from Matched Unrelated and Sibling Donors in Elderly Patients with Acute Myeloid Leukemia - Results of a Retrospective Analysis in 368 Patients.

Purpose: In patients with acute myeloid leukemia (AML) differential indications for matched sibling and unrelated hematopoietic stem cell transplantation (HCT) are considered and arbitrary age limits for HCT exist. We sought to determine whether donor type is a prognostic factor in elderly patients in the era of high-resolution DNA-based HLA-typing.

Patients and Methods: We performed a retrospective cohort analysis in patients with AML older than 50 years who had received an allogeneic HCT between 1995 and 2005. If available, DNA from donors and recipients of unrelated HCT was used for molecular retyping in order to get information on HLA-A, -B, -C, -DRB1 and DQB1 at the allele-level. Donor-recipient pairs with fully matched donors or one mismatch out of ten alleles were considered well-matched.

Results: We identified 368 patients with cytogenetic intermediate or high risk AML who fulfilled the entry criteria. The median age of this cohort of patients was 57 years (range 50 to 73 years). 46% of patients had matched sibling donors, 3% related non-sibling donors, 41% well-matched unrelated donors and 10% poorly matched unrelated donors. In the respective period the percentage of patients with unrelated donors increased from 0% in 1995 to 64% in 2004. High risk features were a history of prior myelodyplasia in 34% of patients, poor risk cytogenetic abnormalities in 33% of patients and a disease status beyond CR1 in 62% of patients. 72% of patients received reduced-intensity conditioning regimens. Peripheral blood stem cells were used as graft in 84% of patients. In multivariate analysis disease status at HCT (p<0.001) and cytogenetic risk (p<0.001) proved to be highly significant predictors, both, for EFS and OS. Whereas, the relative risk of a patient with a well-matched unrelated donor compared to a sibling donor was 0.9 (95% CI, 0.6 to 1.2) for EFS and 1.0 (95% CI, 0.7 to 1.4) for OS. In subgroup analyses EFS was better in AML patients with cytogenetic high risk disease beyond first remission (CR1) (p=0.0147) who had well-matched unrelated donors compared to those with sibling donors and not inferior in any of the other subgroups.

Conclusions: Allogeneic HCT from matched unrelated donors (>=9/10) should be considered equivalent to sibling HCT in terms of survival for patients above the age of 50 years with intermediate or high risk AML. In advanced stages of AML with high risk cytogenetics patients with matched unrelated donors may even have better EFS compared to those with sibling donors.