Novel Scoring System for Ranking Hematopoietic Stem Cell Transplantation

IF 1.9 4区医学 Q2 SURGERY Clinical Transplantation Pub Date : 2024-11-08 DOI:10.1111/ctr.15478

Lee Ann Baxter-Lowe, Tao Wang, Michelle Kuxhausen, Stephen R. Spellman, Martin Maiers, Stephanie Lee, Jennifer Saultz, Esteban Arrieta-Bolaños, Shahinaz M. Gadalla, Yung-Tsi Bolon, Brian C. Betts

{"title":"Novel Scoring System for Ranking Hematopoietic Stem Cell Transplantation","authors":"Lee Ann Baxter-Lowe, Tao Wang, Michelle Kuxhausen, Stephen R. Spellman, Martin Maiers, Stephanie Lee, Jennifer Saultz, Esteban Arrieta-Bolaños, Shahinaz M. Gadalla, Yung-Tsi Bolon, Brian C. Betts","doi":"10.1111/ctr.15478","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>When human leukocyte antigen (HLA)-matched donors are not available for hematopoietic stem cell transplants (HSCT), there are no well-accepted guidelines for ranking 7/8 HLA-matched unrelated donors to achieve optimal transplant outcomes. A novel scoring system for ranking HLA mismatches for these donors was investigated.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>High-resolution HLA types were used to determine amino acid mismatches located in the HLA antigen-recognition domain. The location and physicochemical properties of mismatched amino acids were used to assign scores for peptide binding, T-cell receptor docking, and HLA structure/function. The scores were tested using a cohort of 2319 patients with leukemia or myelodysplastic syndrome who received their first unrelated donor transplant using conventional graft-versus-host disease (GVHD) prophylaxis between 2000 and 2014. Donors were 7/8 HLA-matched with a single HLA Class I mismatch. Primary outcomes were overall survival and acute GVHD.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>The scores did not significantly (<i>p</i> < 0.01) associate with transplant outcomes, although a Peptide Score = 0 (i.e., no differences in peptide binding; <i>N</i> = 146, 6.3%) appears to have lower transplant-related mortality (TRM) compared to higher scores (<i>p</i> = 0.019). HLA mismatches with Peptide Score = 0 were predominately HLA-C*03:03/03:04 (62%), previously reported to be a permissive mismatch, and a group of 28 other HLA mismatches (38%) that showed similar associations with TRM.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>This study suggests that HLA mismatches that do not alter peptide binding or orientation (Peptide Score = 0) could expand the number of permissive HLA mismatches. Further investigation is needed to confirm this observation and to explore alternative scoring systems for ranking HLA mismatched donors.</p>\n </section>\n </div>","PeriodicalId":10467,"journal":{"name":"Clinical Transplantation","volume":"38 11","pages":""},"PeriodicalIF":1.9000,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Transplantation","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/ctr.15478","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"SURGERY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

When human leukocyte antigen (HLA)-matched donors are not available for hematopoietic stem cell transplants (HSCT), there are no well-accepted guidelines for ranking 7/8 HLA-matched unrelated donors to achieve optimal transplant outcomes. A novel scoring system for ranking HLA mismatches for these donors was investigated.

Methods

High-resolution HLA types were used to determine amino acid mismatches located in the HLA antigen-recognition domain. The location and physicochemical properties of mismatched amino acids were used to assign scores for peptide binding, T-cell receptor docking, and HLA structure/function. The scores were tested using a cohort of 2319 patients with leukemia or myelodysplastic syndrome who received their first unrelated donor transplant using conventional graft-versus-host disease (GVHD) prophylaxis between 2000 and 2014. Donors were 7/8 HLA-matched with a single HLA Class I mismatch. Primary outcomes were overall survival and acute GVHD.

Results

The scores did not significantly (p < 0.01) associate with transplant outcomes, although a Peptide Score = 0 (i.e., no differences in peptide binding; N = 146, 6.3%) appears to have lower transplant-related mortality (TRM) compared to higher scores (p = 0.019). HLA mismatches with Peptide Score = 0 were predominately HLA-C*03:03/03:04 (62%), previously reported to be a permissive mismatch, and a group of 28 other HLA mismatches (38%) that showed similar associations with TRM.

Conclusions

This study suggests that HLA mismatches that do not alter peptide binding or orientation (Peptide Score = 0) could expand the number of permissive HLA mismatches. Further investigation is needed to confirm this observation and to explore alternative scoring systems for ranking HLA mismatched donors.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

造血干细胞移植排名的新评分系统。

背景：当没有人类白细胞抗原（HLA）匹配的供者进行造血干细胞移植（HSCT）时，没有公认的指南对7/8 HLA匹配的非亲属供者进行排序，以获得最佳移植结果。方法：利用高分辨率HLA分型确定位于HLA抗原识别结构域的氨基酸错配。利用错配氨基酸的位置和理化性质为肽结合、T 细胞受体对接和 HLA 结构/功能分配分数。2000年至2014年期间，2319名白血病或骨髓增生异常综合征患者接受了首次非亲缘供体移植，并采用了传统的移植物抗宿主病（GVHD）预防措施。供体有7/8个HLA匹配，只有一个HLA I类不匹配。主要结果是总生存率和急性GVHD：结果：得分无明显差异（P这项研究表明，不改变肽结合或取向的 HLA 错配（肽得分 = 0）可增加允许的 HLA 错配的数量。需要进一步调查以证实这一观察结果，并探索对 HLA 错配供体进行排序的其他评分系统。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Clinical Transplantation 医学-外科

CiteScore

3.70

自引率

4.80%

发文量

286

审稿时长

2 months

期刊介绍： Clinical Transplantation: The Journal of Clinical and Translational Research aims to serve as a channel of rapid communication for all those involved in the care of patients who require, or have had, organ or tissue transplants, including: kidney, intestine, liver, pancreas, islets, heart, heart valves, lung, bone marrow, cornea, skin, bone, and cartilage, viable or stored. Published monthly, Clinical Transplantation’s scope is focused on the complete spectrum of present transplant therapies, as well as also those that are experimental or may become possible in future. Topics include: Immunology and immunosuppression; Patient preparation; Social, ethical, and psychological issues; Complications, short- and long-term results; Artificial organs; Donation and preservation of organ and tissue; Translational studies; Advances in tissue typing; Updates on transplant pathology;. Clinical and translational studies are particularly welcome, as well as focused reviews. Full-length papers and short communications are invited. Clinical reviews are encouraged, as well as seminal papers in basic science which might lead to immediate clinical application. Prominence is regularly given to the results of cooperative surveys conducted by the organ and tissue transplant registries. Clinical Transplantation: The Journal of Clinical and Translational Research is essential reading for clinicians and researchers in the diverse field of transplantation: surgeons; clinical immunologists; cryobiologists; hematologists; gastroenterologists; hepatologists; pulmonologists; nephrologists; cardiologists; and endocrinologists. It will also be of interest to sociologists, psychologists, research workers, and to all health professionals whose combined efforts will improve the prognosis of transplant recipients.