Human Leukocyte Antigen Mismatching and Survival in Contemporary Hematopoietic Cell Transplantation for Hematologic Malignancies.

IF 42.1 1区医学 Q1 ONCOLOGY

Journal of Clinical Oncology Pub Date : 2024-08-21 DOI:10.1200/JCO.24.00582

Esteban Arrieta-Bolaños, Edouard F Bonneville, Pietro Crivello, Marie Robin, Tobias Gedde-Dahl, Urpu Salmenniemi, Nicolaus Kröger, Ibrahim Yakoub-Agha, Charles Crawley, Goda Choi, Annoek E C Broers, Edouard Forcade, Martin Carre, Xavier Poiré, Anne Huynh, Stig Lenhoff, Fabio Ciceri, Eleni Tholouli, Thomas Schroeder, Eric Deconinck, Kristina Carlson, Liesbeth C de Wreede, Jorinde D Hoogenboom, Florent Malard, Annalisa Ruggeri, Katharina Fleischhauer

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引用次数: 0

Abstract

Purpose: Human leukocyte antigen (HLA) mismatching can reduce survival of patients with blood cancer after hematopoietic cell transplantation (HCT). How recent advances in HCT practice, in particular graft-versus-host disease (GVHD) prophylaxis by post-transplantation cyclophosphamide (PTCy), influence HLA risk associations is unknown.

Patients and methods: The study included 17,292 unrelated HCTs with 6-locus high-resolution HLA typing, performed mainly for acute leukemia or related myeloid neoplasms between 2016 and 2020, including 1,523 transplants with PTCy. HLA risk associations were evaluated by multivariable Cox regression models, with overall survival (OS) as primary end point.

Results: OS was lower in HLA mismatched compared with fully matched transplants (hazard ratio [HR], 1.23 [99% CI, 1.14 to 1.33]; P < .001). This was driven by class I HLA-A, HLA-B, HLA-C (HR, 1.29 [99% CI, 1.19 to 1.41]; P < .001) but not class II HLA-DRB1 and HLA-DQB1 (HR, 1.07 [99% CI, 0.93 to 1.23]; P = .19). Class I antigen-level mismatches were associated with worse OS than allele-level mismatches (HR, 1.36 [99% CI, 1.24 to 1.49]; P < .001), as were class I graft-versus-host peptide-binding motif (PBM) mismatches compared with matches (HR, 1.42 [99% CI, 1.28 to 1.59]; P < .001). The use of PTCy improved GVHD, relapse-free survival compared with conventional prophylaxis in HLA-matched transplants (HR, 0.77 [0.66 to 0.9]; P < .001). HLA mismatching increased mortality in PTCy transplants (HR, 1.32 [1.04 to 1.68]; P = .003) similarly as in non-PTCy transplants (interaction P = .43).

Conclusion: Class I but not class II HLA mismatches, especially at the antigen and PBM level, are associated with inferior survival in contemporary unrelated HCT. These effects are not significantly different between non-PTCy compared with PTCy transplants. Optimized HLA matching should still be considered in modern HCT.

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当代血液恶性肿瘤造血细胞移植中的人类白细胞抗原不匹配与存活率。

目的：人类白细胞抗原（HLA）不匹配会降低造血细胞移植（HCT）后血癌患者的生存率。最近在造血干细胞移植实践中取得的进展，尤其是通过移植后环磷酰胺（PTCy）预防移植物抗宿主病（GVHD）如何影响 HLA 风险关联尚不清楚：该研究纳入了17,292例进行了6个位点高分辨率HLA分型的非亲缘HCT，主要是在2016年至2020年间进行的急性白血病或相关髓系肿瘤移植，其中包括1,523例进行了PTCy的移植。以总生存期（OS）为主要终点，通过多变量考克斯回归模型评估了HLA风险关联：结果：与完全匹配的移植相比，HLA不匹配的移植患者的OS较低（危险比[HR]，1.23[99% CI, 1.14 to 1.33]；P < .001）。造成这种情况的原因是 I 类 HLA-A、HLA-B、HLA-C（HR，1.29 [99% CI，1.19 至 1.41]；P < .001），而非 II 类 HLA-DRB1 和 HLA-DQB1（HR，1.07 [99% CI，0.93 至 1.23]；P = .19）。与等位基因水平错配相比，I类抗原水平错配与更差的OS相关（HR，1.36 [99% CI，1.24至1.49]；P < .001），与匹配相比，I类移植物抗宿主肽结合基序（PBM）错配与更差的OS相关（HR，1.42 [99% CI，1.28至1.59]；P < .001）。在HLA匹配的移植中，与传统预防相比，使用PTCy可提高GVHD和无复发生存率（HR，0.77 [0.66 to 0.9]；P < .001）。HLA不匹配会增加PTCy移植患者的死亡率（HR，1.32 [1.04 至 1.68]；P = .003），与非PTCy移植患者类似（交互作用P = .43）：结论：第一类而非第二类 HLA 错配（尤其是抗原和 PBM 水平）与当代非亲缘 HCT 的低存活率有关。这些影响在非 PTCy 移植与 PTCy 移植之间没有明显差异。现代 HCT 仍应考虑优化 HLA 匹配。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Clinical Oncology 医学-肿瘤学

CiteScore

41.20

自引率

2.20%

发文量

8215

审稿时长

2 months

期刊介绍： The Journal of Clinical Oncology serves its readers as the single most credible, authoritative resource for disseminating significant clinical oncology research. In print and in electronic format, JCO strives to publish the highest quality articles dedicated to clinical research. Original Reports remain the focus of JCO, but this scientific communication is enhanced by appropriately selected Editorials, Commentaries, Reviews, and other work that relate to the care of patients with cancer.

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