Comparison of Outcomes after UM171-Expanded Cord Blood and Six Conventional Donor Source Transplants: A Matched Analysis from the EBMT Registry

Cord blood (CB) transplantation has fallen into disfavor because of its association with low cell dose and high non-relapse mortality (NRM). However, a phase I to II trial using UM171-expanded CB transplantation in patients with high-risk hematologic malignancies who lacked a suitable donor demonstrated promising results, including prompt neutrophil engraftment, the ability to use smaller, better human leucocyte antigen (HLA)- matched CB units, and a low NRM rate of 5%. This retrospective matched paired analysis was conducted to test the hypothesis that UM171-expanded CB transplantation provides outcomes equivalent or superior to those of conventional hematopoietic stem cell donor sources. The primary objectives were neutrophil engraftment, NRM, and graft versus host disease (GVHD)-free, relapse-free survival (GRFS). This retrospective study compared the outcomes of the 22 adult patients who received a single UM171-expanded CB transplant in the phase I to II trial to those of six cohorts of patients allografted from different stem cell sources, as reported to the European Society for Blood and Marrow Transplantation (EBMT) registry. The six donor control cohorts included: (1) unmanipulated CB, (2) peripheral blood stem cells (PBSC) from a 10/10 HLA-matched unrelated donor (10/10 MUD), (3) bone marrow (BM) from a 10/10 MUD, (4) 9/10 matched unrelated donor (9/10 UD), (5) T cell replete haploidentical (haplo) donor, and (6) HLA- matched sibling donor (MSD). Direct and propensity score matching were used for patient, disease, and transplant characteristics to ensure comparability. The analyzed endpoints included engraftment, GVHD, NRM, relapse, progression-free survival (PFS), overall survival (OS), and GRFS. Neutrophil engraftment was generally similar in all donor groups but was slower for both unmanipulated CB and MUD BM. There was no moderate to severe chronic GVHD in the UM171 CB recipients, with significantly lower rates compared to PBSC MUD, BM MUD, and MSD transplants. PFS, OS, and GRFS were all significantly better with UM171 CB than those seen with haplo donor transplants. GRFS was also consistently superior with UM171 CB when compared to 10/10 MUD PBSC, 9/10 UD, and MSD transplants. UM171-expanded CB recipients have equivalent or improved short- and long-term outcomes compared to patients transplanted from other graft sources.