背景:TCE-3模型的HLA-DPB1非允许性错配(NPMM)的存在与利用移植后环磷酰胺(PTCy)进行单倍体供体移植(HIDT)后的存活率提高有关。最近开发了一个修订的模型(TCE-核心)进一步将TCE-3“第3组”等位基因分为“核心”(C)和“非核心”(NC)等位基因,因此,如果供者和受者中的“第3组”等位基因中的一个或多个等位基因是NC,则以前允许的错配(PMM)现在被认为是C-NPMM。
目的:我们的目的是研究HLA-DPB1C-NPMM根据TCE-Core算法的附加效应,以及失配的方向向量,HIDT后的移植结果。
方法:为此,242个连续的HIDT收件人,所有,分析了2005年至2021年之间(中位年龄51[19,80])的AML或MDS移植。中位随访时间为62[23,199]个月。在TCE-3分类为PMM的136例移植中,有73例被TCE-Core算法重新分类为C-NPMM,其中36个在GVH-载体中(37个仅为HVG)。考虑到常规NPMM和C-NPMM之间的可比较生存率,GVH/双向分析(非允许)。仅HVG的C-NPMM与HLA-DPB1匹配和PMM(允许)组合,因为结果相似。
结果:TCE-Core定义的非许可性HLA-DP不匹配的存在导致5年OS(66%vs.47%)和DFS(60%与43%)。与传统的TCE-3算法相比,TCE-Core确定了更多的非许可移植(38%与23%),并且在非允许性与允许状态(使用TCE-Core与使用TCE-Core的生存结局差异较大TCE-3,OSΔ为18.3%,与12.7%;DFSΔ为16.5%,与8.5%)。在多变量分析中,非允许的TCE核心不匹配导致改进的OS(HR0.54,p=0.003)和DFS(HR0.62,p=0.013),在很大程度上归因于复发风险降低(HR0.63,p=0.049).相比之下,NRM或GVHD结果没有显著影响。
结论:总之,非许可性TCE-核心HLA-DP错配的存在强烈预测基于PTCy的HIDT后的生存率,由于复发风险降低,而GVHD或NRM没有相应增加。作为捐赠者选择工具,TCE-Core似乎可以更好地区分HIDT结果,同时可以识别更大百分比的潜在供体库。
The presence of an HLA-DPB1 nonpermissive mismatch (NPMM) by the TCE-3 model has been associated with improved survival following haploidentical donor transplantation (HIDT) using post-transplantation cyclophosphamide (PTCy). With the development of a revised model (TCE-Core) that further separates TCE-3 \"group 3\" alleles into \"core\" (C) and \"noncore\" (NC) alleles, a formerly permissive mismatch (PMM) resulting from group 3 alleles in both donor and recipient is now considered a C-NPMM if 1 or more of those alleles is NC. We aimed to study the additional effect of HLA-DPB1 C-NPMM according to the TCE-Core algorithm, as well as the directional vector of the mismatch, on outcomes following HIDT. To this end, we analyzed 242 consecutive HIDT recipients with acute leukemia or myelodysplastic syndrome who underwent transplantation between 2005 and 2021 (median age, 51 years; range, 19 to 80 years). The median follow-up was 62 months (range, 23 to 199 months). Of the 136 HIDTs classified as PMM by TCE-3, 73 were reclassified as a C-NPMM by the TCE-Core algorithm, of which 36 were in the graft-versus host (GVH) vector (37 were host-versus-graft [HVG] only). Given comparable survival between conventional NPMM and C-NPMM, GVH/bidirectional were analyzed together (nonpermissive). HVG-only C-NPMM were combined with HLA-DPB1-matched and PMM (permissive) because of similar outcomes. The presence of a TCE-Core-defined nonpermissive HLA-DP mismatch resulted in superior 5-year overall survival (OS) (66% versus 47%) and disease-free survival (DFS) (60% versus 43%). Compared to the conventional TCE-3 algorithm, TCE-Core identified a higher percentage of nonpermissive transplants (38% versus 23%) and better discriminated outcomes between nonpermissive and permissive status, with a larger difference in survival outcomes using TCE-Core compared to TCE-3 (OS Δ, 18.3% versus 12.7%; DFS Δ, 16.5% versus 8.5%). In multivariable analysis (MVA), a nonpermissive TCE-Core mismatch led to improved OS (hazard ratio [HR], .54; P = .003) and DFS (HR, .62; P = .013), largely due to decreased relapse risk (HR, .63; P = .049). In contrast, nonrelapse mortality (NRM) and graft-versus-host disease (GVHD) outcomes were not significantly impacted. In summary, the presence of nonpermissive TCE-Core HLA-DP mismatch strongly predicts survival following PTCy-based HIDT, owing to a reduction in relapse risk without a corresponding increase in GVHD or NRM. As a donor selection tool, TCE-Core appears to better discriminate HIDT outcomes while at the same time identifying a larger percentage of the potential donor pool.