Matched and Mismatched Unrelated Donor Versus Unmanipulated Haploidentical Donors for Hematopoietic Cell Transplantation in Acute Leukemia in Remission: A Pair Matched Analysis on Behalf of the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT)

Background. The best donor source for adult patients with acute leukemia lacking an HLA-identical donor still remains to be established. The objective of this study was to compare the outcome after T-cell-replete hematopoietic stem cell transplantation from haploidentical donor (HAPLO) and transplant from Matched Unrelated Donor (MUD) or Mismatched Unrelated Donor at a single HLA-locus (MMUD) for patients with acute leukemia in remission.

Methods. From January 2007 to December 2012, 313 consecutive HAPLOs were performed as first allogeneic transplants in adult patients with de novo acute leukemia in CR1 or CR2 and reported to the EBMT Registry. We were able to pair match 273 of these 313 patients with another 273 patients who received a MUD and 273 who received a MMUD transplant. The matching factors were as follow: age (+/-5y), diagnosis (myeloid or lymphoblastic leukemia), disease status at transplant (CR1 or CR2) and interval from diagnosis to transplant (+/-1mo).

Results. The median follow-up was 22 months. The two-year non-relapse mortality (NRM) and relapse (RI) cumulative incidences were 28% and 30% for HAPLO, 21% and 19% for MUD, and 28% and 27% for MMUD. The two-year KM estimates of leukemia-free survival (LFS) and overall survival (OS) were 42% and 49% for HAPLO, 59% and 65% for MUD, 45% and 51% for MMUD. In multivariate analysis both NRM and RI were significantly reduced in MUD compared to HAPLO (NRM, hazard ratio (HR): 0.61, p=0.02, 95%CI: 0.40-0.91; RI, HR: 0.59, p=0.01, 95%CI: 0.39-0.89) but there was no statistical difference between HAPLO and MMUD (NRM, p=0.59; RI, p=0.52). LFS and OS were significantly higher in MUD compared to HAPLO (LFS HR: 0.61, p=0.001, 95%CI: 0.45-0.81.OS HR: 0.63, p=0.004, 95%CI: 0.46-0.86) but not statistically different between MMUD and HAPLO (LFS, p=0.45. OS, p=0.84). Of note, type of donor was neither associated with day-100 grade II-IV acute graft-versus-host disease, nor to chronic graft-versus-host disease.

Conclusion. These findings suggest that LFS and OS were significantly higher in patients with acute leukemia in remission receiving a MUD compared to patients with similar characteristics receiving a HAPLO. We didn’t find significant differences between MMUD and HAPLO. In the absence of a MUD, host/donor features and urgency of transplant should drive us towards the best choice between these alternative donor sources.