Allele-level HLA matching for umbilical cord blood transplantation for non-malignant diseases in children: a retrospective analysis.
Allele-level HLA matching for umbilical cord blood transplantation for non-malignant diseases in children: a retrospective analysis.
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DOI：
10.1016/s2352-3026(17)30104-7
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发表时间：
2017-07
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影响因子：
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通讯作者：
Ruggeri A
中科院分区：
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作者：
Eapen M;Wang T;Veys PA;Boelens JJ;St Martin A;Spellman S;Bonfim CS;Brady C;Cant AJ;Dalle JH;Davies SM;Freeman J;Hsu KC;Fleischhauer K;Kenzey C;Kurtzberg J;Michel G;Orchard PJ;Paviglianiti A;Rocha V;Veneris MR;Volt F;Wynn R;Lee SJ;Horowitz MM;Gluckman E;Ruggeri A
选择用于移植治疗非恶性疾病的无关脐带血单位的标准依赖于HLA-A和-B的抗原水平（较低分辨率）人类白细胞抗原（HLA）分型以及HLA-DRB 1的等位基因水平。我们的目的是研究HLA-A、-B、-C和-DRB 1等位基因水平匹配对脐带血移植治疗非恶性疾病的影响。我们回顾性研究了1199例等位基因水平HLA配型的儿童供受者对，他们因非恶性疾病接受了单单位脐带血移植，报告给国际血液和骨髓移植研究中心或Eurocord/欧洲血液和骨髓移植组。移植发生在2000年1月1日至2012年12月31日之间。主要结局是总生存期。使用考克斯回归模型研究HLA配型对生存率的影响。与HLA匹配的移植相比，两个月后移植不匹配的死亡率更高，（风险比[HR] 1.55，95%CI 1.08 - 2.21，p = 0.018），3个（HR 2.04，95%CI 1.44 - 2.89，p = 0.0001）和≥ 4个等位基因（HR 3.15，95%CI 2.16 - 4.58，p <0.0001）。在一个等位基因匹配和不匹配的移植之间，死亡率没有显著差异（HR 1.18，95% CI 0.80 - 1.72，p = 0.388）。其他与高死亡率相关的因素包括受体巨细胞病毒血清阳性（HR 1.40，95% CI 1.13 - 1.74，p = 0.002），与清髓性预处理方案相比强度降低（HR 1.36，95% CI 1.10 - 1.68，p = 0.004），移植单位总有核细胞剂量> 21 × 107/kg与≤> 21 × 107/kg相比（HR 1.47，95% CI 1.11 - 1.95，p = 0.008），2000 - 2005年与2006 - 2012年相比进行的移植（HR 1.64，95% CI 1.31 - 2.04，p <0.0001）。根据受者巨细胞病毒血清状态、预处理方案强度、总有核细胞剂量和移植时间调整后的5年总生存率为79%（95% CI 74 - 85）HLA匹配后，76%（95% CI 71 - 81）1个等位基因错配后，70%在2个等位基因错配后为62%（95% CI 57 - 68），在≥ 4个等位基因错配移植后为49%（95% CI 41 - 57）。移植失败是死亡的主要原因。这些数据支持从目前的做法，选择无关的脐带血单位移植的非恶性疾病必须考虑等位基因水平的HLA匹配在HLA-A，-B，-C和-DRB 1的变化。国家癌症研究所、国家心肺血液研究所、国家过敏和传染病研究所、美国卫生与公众服务部-卫生资源和服务管理局和美国海军部
The standard for selecting unrelated umbilical cord blood units for transplantation for nonmalignant diseases rely on antigen-level (lower resolution) human leukocyte antigen (HLA) typing for HLA-A and –B and allele-level for HLA-DRB1. Our aim was to study the effects of allele-level matching at HLA-A, -B, -C and –DRB1, the standard for adult unrelated volunteer donor transplantation for nonmalignant diseases for umbilical cord blood transplantation. We retrospectively studied 1199 pediatric donor-recipient pairs with allele-level HLA matching who received a single unit umbilical cord blood transplant for nonmalignant diseases reported to the Center for International Blood and Marrow Transplant Research or Eurocord/European Group for Blood and Marrow Transplant. Transplantations occurred between January 1, 2000 and December 31, 2012. The primary outcome was overall survival. The effect of HLA matching on survival was studied using a Cox regression model. Compared to HLA-matched transplants, mortality was higher with transplants mismatched at two (hazard ratio [HR] 1·55, 95% CI 1·08 – 2·21, p=0·018), three (HR 2·04, 95% CI 1·44 – 2·89, p=0·0001) and ≥four alleles (HR 3·15, 95% CI 2·16 – 4·58, p<0·0001). There were no significant differences in mortality between transplants that were matched and mismatched at one allele (HR 1·18, 95% CI 0·80 – 1·72, p=0·388). Other factors associated with higher mortality included recipient cytomegalovirus seropositivity (HR 1·40, 95% CI 1·13 – 1·74, p=0·002), reduced intensity compared to myeloablative conditioning regimens (HR 1·36, 95% CI 1·10 – 1·68, p=0·004), transplantation of units with total nucleated cell dose >21 × 107/kg compared to ≤>21 × 107/kg (HR 1·47, 95% CI 1·11 – 1·95, p=0·008) and transplants performed in 2000 – 2005 compared to 2006 – 2012 (HR 1·64, 95% CI 1·31 – 2·04, p<0·0001). The 5-year overall survival adjusted for recipient cytomegalovirus serostatus, conditioning regimen intensity, total nucleated cell dose and transplant period was 79% (95% CI 74 – 85) after HLA matched, 76% (95% CI 71 – 81) after 1 allele mismatched, 70% (95% CI 65 – 75) after 2 allele mismatched, 62% (95% CI 57 – 68) after 3 allele mismatched and 49% (95% CI 41 – 57) after ≥4 allele mismatched transplants. Graft failure was the predominant cause of mortality. These data support a change from current practice in that selection of unrelated umbilical cord blood units for transplantation for nonmalignant diseases must consider allele-level HLA matching at HLA-A, -B, -C and –DRB1. National Cancer Institute, National Heart, Lung, and Blood Institute, National Institute for Allergy and Infectious Diseases, US Department of Health and Human Services - Health Resources and Services Administration and US Department of Navy