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HLA discrepancy and outcome of second HSCT
Figure 1. The unadjusted cumulative incidence of grades III to IV acute graft-versus-host disease (GvHD) by HLA mismatch (MM) for graft. With regard to the graft-versus-host results, the unadjusted cumulative incidence rates of grade III-IV acute GvHD were 9.5% (95%CI: 4.4-17.0%) in the 0 MM group, 13.8% (95%CI: 9.0%–19.7%) in the 1 MM group, and 11.0% (95%CI: 8.2%– 14.3%) in the ≥ 2 MM group.
(0 MM, 0.0%; 1 MM, 11.8%; ≥2 MM 10.9%) were increased in the 1 MM group and the ≥2 MM group (Online Supplementary Table S3). With regard to the graft-versus-first donor outcomes, there were no signifi- cant differences in TRM, relapse, or OS among the three groups (Table 4). In addition, no allele MM was associated with relapse, TRM, or OS in the analysis of each HLA allele MM (Online Supplementary Table S2).
Analyses by stem cell sources
Finally, we performed analyses according to stem cell source (Online Supplementary Tables S4 and 5). We did not observe any obvious statistically heterogeneity among stem cell sources. However, the small sample size for some categories partially precluded evaluation of signifi- cance.
Discussion
There have been several studies on the role of donor change in the outcome of second HSCT; however, these studies were performed mainly in HLA-matched or 1 Ag- MM cases and focused on procedures in which a second HSCT from the same donor was performed.1-9 In this study, we evaluated the role of HLA discrepancy between the graft and host and between the graft and the first donor on the outcome of second HSCT after HLA-MM initial HSCT. On evaluating 646 recipients of a second HSCT, it was found that graft-host HLA-match was asso- ciated with a reduced rate of TRM compared to HLA- MM, while HLA discrepancy between the graft and the first donor had no impact on the outcome of second HSCT.
In the largest retrospective analysis performed to date (n=1285 patients) to compare the incidence of GvHD in the same cohort, the incidence rate of grade II-IV acute GvHD in first HSCT was 26% versus 46% in second HSCT.24 In our study, the incidence of grade II-IV and
Figure 2. The unadjusted cumulative incidence of relapse by HLA mismatch (MM) for graft-versus-host. With regard to the graft-versus-host results, the unadjusted cumulative incidence rates of relapse were 55.6% (95%CI: 43.9- 65.7%) in the 0 MM group, 45.2% (95%CI: 37.3-52.8%) in the 1 MM group, and 46.8% (95%CI: 41.8-51.7%) in the ≥ 2 MM group.
Figure 3. The unadjusted cumulative incidence of transplant-related mortality (TRM) by HLA mismatch (MM) for graft-versus-host. With regard to the graft-ver- sus-host results, the unadjusted cumulative incidence rates of treatment-relat- ed mortality TRM were 19.8% (95%CI: 11.8-29.2%) in the 0 MM group, 32.5% (95%CI: 25.2-39.9%) in the 1 MM group, and 34.7% (95%CI: 30.0-39.4%) in the ≥ 2 MM group.
grade III-IV acute GvHD for first HSCT was 36.4% and 9.0% versus 34.2% and 11.2%, respectively, for second HSCT. Due to the higher rate of GvHD for second HSCT, prevention of acute GvHD represents an important, and as yet unmet, medical need.
Experimental murine studies reported that hematopoi- etic APCs play an important role in the induction of acute GvHD in an MHC MM setting.13-16
In the present study, HLA-MM between the graft and first donor was not associated with an increased risk of acute GvHD in HSCT recipients having hematopoietic
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