193 The Impact of HLA Mismatch Only in the Host-Versus-Graft Direction on the Outcome of Related Hematopoietic Stem Cell Transplantation for Patients with HLA-Homozygous Haplotypes: A Retrospective Analysis of the JSHCT HLA Working Group Study

Track: Poster Abstracts
Wednesday, February 11, 2015, 6:45 PM-7:45 PM
Grand Hall CD (Manchester Grand Hyatt)
Junya Kanda, MD , Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan
Kazuhiro Ikegame, MD, PhD , Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
Shigeo Fuji, MD , Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan
Takahiro Fukuda, MD, PhD , Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan
Mineo Kurokawa, MD , Department of Cell Therapy and Transplantation Medicine, The University of Tokyo Hospital, Tokyo, Japan
Hiroyasu Ogawa, MD, PhD , Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
Kazuteru Ohashi , Division of Hematology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan
Heiwa Kanamori, MD , Department of Hematology, Kanagawa Cancer Center, Kanagawa, Japan
Jun Ishikawa, MD , Department of Hematology and Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan
Masami Inoue, MD , Department of Hematology/Oncology, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan
Tatsuo Ichinohe, MD , Department of Hematology and Oncology, Hiroshima University Hospital, Hiroshima, Japan
Yoshiko Atsuta, MD, PhD , Department of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya, Japan
Yoshinobu Kanda, MD , Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan
Presentation recording not available for download or distribution as requested by the presenting author.
Background: Almost 1% of the Japanese population has HLA-homozygous haplotypes (the same HLA haplotypes). An HLA mismatch between patients with HLA-homozygous haplotypes and their children or parents is absent in the graft-versus-host (GVH) direction. Hematopoietic stem cell transplantation (SCT) from a haploidentical donor with HLA mismatch only in the host-versus-graft (HVG) direction was feasible using standard GVHD prophylaxis (Ikegame K, et al. IJH 2012). However, this should be validated in a larger cohort.

Methods: We analyzed 229 patients with hematologic malignancies who had homozygous HLA-A, -B, and -DR antigens and received their first allogeneic SCT from a related donor without an HLA mismatch in the GVH direction between 1998 and 2012 in Japan. In total, 155 patients received SCT from an HLA-matched related donor (homo-to-homo SCT) and 74 received SCT from a haploidentical donor with HLA mismatch only in the HVG direction (hetero-to-homo SCT). High-risk disease and the use of tacrolimus were more frequently observed in the hetero-to-homo SCT group. The number of HLA mismatches in the HVG direction was 1 in 16 patients, 2 in 27 patients, and 3 in 31 patients. The impact of hetero-to-homo versus homo-to-homo SCT was analyzed after adjusting for transplant year, age, and other significant variables.

Results: There was no significant difference in the cumulative incidence of neutrophil engraftment and severe acute GVHD between the hetero-to-homo and homo-to-homo SCT groups (neutrophil engraftment at 50 days, 91% vs. 95%; adjusted hazard ratio (aHR) 1.05, P = 0.768; severe acute GVHD at 100 days, 10% vs. 5%; aHR 1.68, P = 0.320). Non-relapse mortality was significantly higher in the hetero-to-homo SCT group than in the homo-to-homo SCT group (26% vs. 10% at 5 years; aHR 2.42, P = 0.013), whereas there was no significant difference in the relapse rate. This resulted in non-significant lower overall survival in the hetero-to-homo SCT group (35% vs. 57% at 5 years; aHR 1.41, P = 0.083).

Conclusions: Hetero-to-homo SCT is usually considered only when transplantation should be performed immediately for high-risk disease. Therefore, differences in patient background between the homo-to-homo and hetero-to-homo SCT groups may have biased the comparison. However, it should be noted that there was no significant difference in neutrophil engraftment as well as severe acute GVHD. Although non-relapse mortality and overall mortality rates were higher in the hetero-to-homo SCT group than in the homo-to-homo SCT group, hetero-to-homo SCT may be considered when immediate transplantation is required but an appropriate alternative donor is not available otherwise.

Disclosures:
Nothing To Disclose
See more of: Poster Session 1: Histocompatibility/Alternative Stem Cell Sources
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