Impact of Different Donor Types on Post-Transplant Disease Control in Patients with MDS Receiving Anti-Thymocyte Globulin (ATG)-Containing Conditioning

Background HLA-matched sibling donor (MSD), if available, is generally considered as the first candidate in the process of donor selection for allogeneic hematopoietic stem cell transplantation (HSCT). However, recent improvement of unrelated donor (UD) or haploidentical donor (HID) transplant outcomes by using ATG- or PTCy-based conditioning can be a challenge to this traditional donor search process that always prioritizes MSD. This study was designed to compare the influences of donor types on post-HSCT outcomes in patients with MDS receiving anti-thymocyte globulin (ATG)-containing conditioning

Methods Consecutive 397 patients receiving fludarabine-busulfan based conditioning regimens for MDS between May 2009 and Dec 2019 were enrolled. Transplant outcomes, including overall survival (OS), relapse free survival (RFS), and cumulative incidence of relapse (CIR), non-relapse mortality (NRM) and graft versus host disease (GVHD) were compared according to donor types.

Results The most common MDS subtypes were MDS-EB1 (n=106, 26.7%) and EB-2 (n=166, 41.8%) and the median age at HSCT was 50 years (range, 19 to 72 years). Majority of patients (n=299, 75.3%) received reduced intensity conditioning and 159 (40.1%), 136 (34.3%) and 102 (25.7%) patients in each underwent MSD, UD and HID transplantion. Overall, after the median follow up of 85.3 months, the median OS and RFS were not reached. And the probabilities of OS, RFS, CIR and NRM at 5-years were 62.6%, 58.4%, 23.4% and 18.2%, respectively. By the donor types, the MSD group showed a significantly inferior OS (P=0.021) and RFS (P=0.033) than the remaining patients. While NRM was not significantly different between the MSD, UD, and HID groups (p=0.329, MSD vs MUD, p=0.329; MSD vs HID, p=0.097; MUD vs HID, p=0.437)), the CIR was significantly higher in the MSD group when compared to either MUD (p=0.004) or to HID (p<0.001. Overall, the cumulative incidence of grade II-IV acute GVHD was significantly lower in MSD compared to UD (P=0.03) and HID (P<0.001) as was moderate to severe chronic GVHD of MSD group compared to the other patients (P=0.018). After adjusting for other clinical factors, donor type remained significant for OS, RFS and CIR in multivariate analysis, and HSCT from MSD showed the worst post-transplant outcomes (p=0.011, HR=1.52 for OS; p=0.017, HR=1.46 for RFS; p=0.001, HR=1.97 for CIR).

Conclusions Our data indicates that post-HSCT outcomes could be differently affected by the donor types and was better in patients with either MUD or HID rather than with MSD among the MDS patients receiving HSCT using ATG-containing conditioning.

No relevant conflicts of interest to declare.