HLA haploidentical stem cell transplantation from HLA homozygous donors to HLA heterozygous donors may have lower survival rates than haploidentical transplantation from HLA heterozygous donors to HLA heterozygous donors: a retrospective nationwide analysis

• Published in: International journal of hematology Vol. 119; no. 2; pp. 173 - 182
• Main Authors: Fukunaga, Keiko, Ikegame, Kazuhiro, Nakamae, Hirohisa, Doki, Noriko, Fukuda, Takahiro, Kondo, Yukio, Ara, Takahide, Eto, Tetsuya, Mori, Yasuo, Matsuoka, Ken-ichi, Kanda, Yoshinobu, Onizuka, Makoto, Atsuta, Yoshiko, Ichinohe, Tatsuo, Morishima, Satoko, Kanda, Junya
• Format: Journal Article
• Language: English
• Published: Singapore Springer Nature Singapore 01.02.2024; Springer Nature B.V
• Subjects: Animals; Graft versus host disease; Graft vs Host Disease - etiology; Graft-versus-host reaction; Graft-versus-leukemia reaction; Grafting; Haplotypes; Hematology; Hematopoietic Stem Cell Transplantation - adverse effects; Histocompatibility antigen HLA; Humans; Leukemia; Leukocytes (neutrophilic); Medicine; Medicine & Public Health; Mice; Oncology; Original Article; Retrospective Studies; Stem cell transplantation; Stem cells; Survival; Survival Rate; Transplantation; Transplantation, Haploidentical - adverse effects; Transplants; Homo-to-hetero; Hetero-to-hetero; HLA; Haploidentical transplantation
• ISSN: 0925-5710; 1865-3774
• DOI: 10.1007/s12185-023-03693-w

In HLA haploidentical stem cell transplantation, patients and donors usually share one HLA haplotype and have one different HLA haplotype (hetero-to-hetero). However, there are rare cases of transplantation from HLA homozygous donors to heterozygous recipients (homo-to-hetero), resulting in mismatches only in the graft-versus-host direction. We previously reported that homo-to-hetero transplants have a lower survival rate in a mouse model than hetero-to-hetero transplants due to stronger graft-versus-host disease (GVHD) but inferior graft-versus-leukemia effect. To examine whether homo-to-hetero transplant effects also occur in humans, we retrospectively compared the results of 59 homo-to-hetero and 4,539 hetero-to-hetero cases in the Japanese transplant registry data. The results showed no statistical difference between the homo-to-hetero and hetero-to-hetero groups in the cumulative incidences of neutrophil engraftment (83.1% vs 89.0%), acute GVHD II–IV (36.8% vs 38.8%), III–IV (16.8% vs 17.4%), chronic GVHD (32.7% vs 30.7%), relapse (52.9% vs 49.0%), and non-relapse mortality (31.6% vs 28.2%). In contrast, overall survival was significantly lower in the homo-to-hetero group than in the hetero-to-hetero group (12.6% vs 26.2%, p  = 0.0308). The inferior effect of homo-to-hetero transplantation on overall survival remained significant in multivariate analyses.