Young (<35 years) Haploidentical Versus Old (>35 years) Mismatched Unrelated Donors and Vice Versa for Allogeneic Stem Cell Transplantation with post-Transplant Cyclophosphamide in Patients with Acute Myeloid Leukemia in First Remission: a Study on Behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

Background Whether the choice between haploidentical (haplo) vs. mismatched) (8-9/10) unrelated donors (MMUD) for transplantation (HSCT) with post-transplant cyclophosphamide (PTCy) should be based in part on donors being younger, is unknown. Methods The study aimed to assess whether a younger haplo donor (yH), aged <35 years (median donor age of the study population), be preferred over an older (≥35 years) MMUD (oMMUD) and vice versa, should a young MMUD (yMMUD) be preferred over an older haplo donor (oH) in AML patients (pts) undergoing HSCT in CR1 with PTCy. Results The first comparison included 1212 pts, 1065 (88%) yH, and 147 oMMUD. Median FU was 27.1 (IQR, 24.5-29.6) and 22.5 (IQR, 14.5-29.7) months(mos) (p<0.0007). Median pt age was 56.5 (range 18.1-81.8) vs. 55.1 (20.2-73.3) years (p=0.49), while the median donor age was 27.8 (range 18-35) vs. 41.8 (range 35-59.1) years. HSCTs from MMUD were performed more recently, 2020 vs. 2019 (p=0.002). BM was the more frequent graft source in haplo 27.6% vs. 3.4% (p<0.0001). All other pt and transplant parameters did not differ significantly between the two cohorts. In MVA, aGVHD grade II-IV was significantly lower in HSCT from yH vs. oMMUD, hazard ratio (HR)=1.62 (95% CI 1.14-2.31, p=0.007). All other outcome parameters including severe aGVHD, chronic GVHD, NRM, RI, LFS, OS, and GRFS did not differ (Figure 1A, B). The second comparison included 1586 pts, 1315 oH and 271 yMMUD. Median FU was 31.8 (IQR, 29.9-34.2) and 19.8 (IQR, 14.9-24) mos (p<0.0001). Median pt age was 57.9 (range 18.1-82.5) vs. 55.8 (18.1-75.6) years (p=0.19), while the median donor age was 45 (range 35-73.3) vs. 25.8 (range 18.4-34.9) years. HSCTs from MMUD were performed more recently, 2020 vs.2019 (p=0.002). More pts in the oH group had de novo AML 86.6% vs. 81.9% in the yMMUD group. More pts and donors in the oH group were CMV seropositive, 79.7% and 68.2% vs. 71.3% and 42.1% in the yMMUD group (p=0.02; p<0.0001). MAC was more frequent in the yMMUD group 53.3% vs. 46.8% in the oH group (p=0.049). BM was more often used in haplo (27%) than in MMUD (4.4%) grafts (p<0.0001). Other pt and transplant parameters did not differ significantly. In MVA, aGVHD grade II-IV but not grade III-IV or chronic GVHD was significantly lower in HSCT from yMMUD vs. oH, HR=0.69 (95% CI 0.51-0.92, p=0.013). NRM was also lower in HSCT from yMMUD vs. oH, HR=0.6 (95% CI 0.38-0.93, p=0.022). All other outcomes including RI, LFS, OS, and GRFS did not differ (Figure 1C, D). Conclusions In this retrospective analysis of alternative donor HSCT with PTCy in pts with AML in CR1, comparing young haplo or MMUD vs. old MMUD or haplo donors, we demonstrated that yH donor vs. oMMUD and yMMUD vs. oH resulted in a lower incidence of grade II-IV aGVHD. In addition, transplants from yMMUD vs. oH resulted in lower NRM. Thus, a younger donor (<35 years) is preferable for alternative donor transplants, a finding that may assist in choosing an alternative donor.