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The Impact of HLA-Mismatch Direction on the Outcome of Unrelated Bone Marrow Transplantation: A Retrospective Analysis from the JSHCT HLA Working Group

Track: BMT Tandem "Scientific" Meeting
Saturday, March 1, 2014, 4:45 PM-6:45 PM
Texas B (Gaylord Texan)
Junya Kanda, MD, PhD , Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan
Yoshinobu Maeda, MD , Department of Hematology and Oncology, Okayama University Graduate School, Okayama, Japan
Kazuteru Ohashi , Division of Hematology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan
Takahiro Fukuda, MD , Department of Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan
Koichi Miyamura , Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan
Shin-Ichiro Mori, MD , Hematology-Oncology Department, St Luke's International Hospital, Tokyo, Japan
Yasuo Morishima , Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan
Yoshiko Atsuta, MD, PhD , Department of HSCT, Data Management / Biostatistics, Nagoya University Graduate School of Medicine, Nagoya, Japan
Yoshinobu Kanda , Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan
Audio File Recorded Presentation
Backgrounds: In a recent study by the CIBMTR (Blood 2013), stem cell transplantation (SCT) from an unrelated donor with bidirectional 1-locus mismatch (1MM-Bi) or a donor with 1-locus mismatch only in the graft-versus-host (GVH) direction (1MM-GVH) was significantly associated with higher risks of overall mortality and severe acute GVHD than SCT from an unrelated donor with an HLA-A, -B, -C, -DRB1 8/8 allele match (0MM). However, SCT from a donor with 1-locus mismatch only in the host-versus-graft (HVG) direction (1MM-HVG) was not associated with these risks. Therefore, selection of an unrelated donor with 1MM-HVG was recommended when an 8/8-allele matched donor is not available. However, the effect of HLA-mismatch direction needs to be validated in other populations.

Methods: We analyzed adult patients with leukemia or myelodysplastic syndrome who received the first allogeneic SCT from an 8/8-allele matched or a 7/8-allele matched unrelated donor between 2000 and 2011 in Japan. The effect of 1MM-Bi (n=1020), 1MM-GVH (n=83), or 1MM-HVG (n=83) as compared with that of 0MM (n= 2570) was analyzed after adjusting for other significant variables. For multiple comparisons, a value of P < 0.01 was used to determine statistical significance.

Results: The risk of overall mortality was significantly higher in the 1MM-Bi group than in the 0MM group (hazard ratio [HR] 1.32, P<0.001), while there was no difference between the 1MM-GVH (HR 0.98, P = 0.894) or 1MM-HVG group (HR 1.15, P=0.368) and the 0MM group. There were no significant differences in overall survival (OS) rates among the 1MM-Bi, 1MM-HVG, and 1MM-GVH groups. Further, we observed no significant differences in the non-relapse mortality (NRM) and relapse rates between the 0MM group and 1MM-GVH or 1MM-HVG group. The risk of grade 3-4 acute GVHD was higher with a marginal significance in the 1MM-GVH group than in the 0MM group (HR 1.85, P=0.014). There was no significant difference between the 1MM-HVG group and 0MM group (HR 1.25, P=0.468).

Conclusions: Although the risk of severe acute GVHD in the 1MM-GVH group tended to be higher than that in the 0MM group, there was no significant difference in the OS or NRM rates. The 1MM-HVG group also showed an OS rate comparable to that of the 0MM group. Unlike the conclusion drawn by the CIBMTR study, in this study, there is no evidence showing that an unrelated donor with 1MM-HVG should be prioritized over one with 1MM-GVH in a Japanese cohort.

Disclosures:
Nothing To Disclose
See more of: Oral Abstracts - Session K - Histocompatibility & Clinical Cellular Therapy
See more of: BMT Tandem "Scientific" Meeting
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