Impact of Parental Donor Type On Outcomes After HLA-Matched and HLA-Mismatched T-Cell-Replete Hematopoietic Cell Transplantation for Patients with Leukemia: A Retrospective Cohort Study.
Authors: Ichinohe Tatsuo , Kanda Junya , Inagaki Jiro , Inoue Masami , Koh Katsuyoshi , Kikuta Atsushi , Yabe Hiromasa , Tanaka Junji , Atsuta Yoshiko , Kanda Yoshinobu 
Published: October 2019

Abstract
Abstract 3113
During pregnancy, women can develop both cytotoxic and regulatory immune cells against inherited paternal alloantigens of their fetus. Such immune cells reactive against fetal alloantigens can persist postpartum and may confer beneficial effects when the mother is used as a donor for hematopoietic cell transplantation (HCT) for her offspring. However, there have been few studies that aimed to evaluate the effects of parental donor type on outcomes after HCT performed with T-cell-replete grafts in a relatively large cohort of patients. Using datasets obtained fromthe Japan Society for Hematopoietic Cell Transplantation, we compared the outcomes of 477 patients who received T-cell-replete HCT from a maternal donor (n=305) or a paternal donor (n=172) between 1999 and 2009 as treatment for acute myeloid leukemia (n=203), acute lymphoblastic leukemia (n=213), chronic myelogenous leukemia (n=37), and myelodysplastic syndrome (n=24); in vivo T-cell depletion was employed in 48 patients. Patients who underwent HCT using ex vivo T-cell-depleted grafts were not included in the study. Cox proportional-hazard models were used to evaluate variables that may affect overall mortality, whereas Fine and Gray regression models were used to evaluate variables that may affect incidences of graft-versus-host disease (GVHD), relapse, and treatment-related death. Recipients of maternal donor HCT and paternal donor HCT had similar background characteristics with respect to age group, diagnosis, disease status, stem cell source, type of conditioning regimen, and type of GVHD prophylaxis. Proportions of male recipients (61% of maternal donor HCT vs 51% of paternal donor HCT, p=0.044) and patients given a graft with HLA mismatch in the GVH vector (70% vs 60%, p=0.031) were higher in maternal donor HCT compared with paternal donor HCT. Unadjusted overall survival at 3 years after transplantation were 49.6% after maternal donor HCT and 37.9% after paternal donor HCT (p=0.118). Multivariate analysis revealed a significantly lower oveall mortality after maternal donor HCT compared with paternal donor HCT [hazard ratio (HR) of maternal donor transplant vs paternal donor transplant, 0.70; p=0.008]; the use of a maternal donor was associated with a lower risk of treatment-related mortality (TRM) (HR, 0.62; p=0.018) and a higher incidence of chronic GVHD (HR, 1.43; p=0.036), whereas the incidence rates of grade 2–4 acute GVHD (HR, 1.06; p=0.690) and relapse (HR, 1.05; p=0.763) were similar between the two groups. Intriguingly, if the analysis is confined to 241 patients who developed grades 2 to 4 acute GVHD, the use of a maternal donor was associated with a lower TRM compared with the use of a paternal donor (HR, 0.55; p=0.028), suggesting protective effects of maternal grafts in the setting of acute GVHD. Of 159 patients who received grafts without mismatch at HLA-A, -B, and -DR antigens in the GVH vector, overall mortality (HR, 0.86; p=0.535) and TRM (HR, 0.98; p=0.956) were similar between the two groups. Of 318 patients who received grafts with 1 (n=202) or more (n=116) HLA antigen mismatch in the GVH vector, the use of maternal grafts was associated with a lower overall mortality (HR, 0.63; p=0.004) and a lower TRM (HR, 0.53; p=0.005) compared with the use of paternal grafts. Collectively, these results indicate that the use of an HLA-mismatched mother as a donor for T-cell-replete HCT can be a reasonable option in selected patients who lack a suitable conventional stem cell source.

Disclosures:
No relevant conflicts of interest to declare.