Comparison of Long-Term Outcomes of Double Unit Cord Blood Versus Haploidentical Donor Transplantation in Adult Patients With Acute Lymphoblastic Leukemia Regarding KIR-Ligand Mismatch

Background: Haploidentical donor transplantation (HIDT) or cord blood transplantation (CBT) are common alternatives for patients lacking human-leukocyte antigen (HLA)-matched donors. In addition to the donor source, NK cell alloreactivity due to HLA-mismatch setting may affect outcomes in alternative-donor hematopoietic cell transplantation (HCT). However, a limited number of studies have evaluated their impacts in adult acute lymphoblastic leukemia (ALL). Objectives: We aimed to assess the effects of donor source and KIRL-MM on outcomes of alternative-donor HCT, with a special focus on adult ALL. Study Design: We retrospectively compared clinical outcomes between HIDT (n=47) and double unit CBT (DCBT) (n=134). Patients received fludarabine and busulfan-based reduced toxicity conditioning before HIDT, and TBI-based myeloablative conditioning before DCBT. KIR ligands were determined using a web-based calculator. For DCBT, donor KIR ligand groups were defined by the dominant CB unit after engraftment. Results: After a median follow-up of 39.4 months, DCBT showed higher 3-year non-relapse mortality (NRM) (22.8% vs. 9.0%, p=0.038), whereas the cumulative incidence of relapse (CIR) was significantly higher in HIDT (47.9% vs. 18.9%, p<0.001). Estimated disease-free survival (DFS) was comparable (DCBT 58.5% vs. HIDT 44.3%, p=0.106). GVH direction KIRL-MM showed lower incidence of acute GVHD in both HIDT and DCBT. However, GVH direction KIRL-MM was associated with poorer DFS (37.2% vs. 66.0%, p=0.008) only in the DCBT subgroup, mostly due to specifically higher NRM rate (35.0% vs 18.4%, p=0.057). Conclusion: Our study supports the usefulness of DCBT in the HIDT-dominant era and suggests potential ways to improve survival outcomes of DCBT.