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Donor-specific anti-human leukocyte antigen antibodies were associated with primary graft failure after unmanipulated haploidentical blood and marrow transplantation: a prospective study with randomly assigned training and validation sets
Chang, Ying-Jun1,3; Zhao, Xiang-Yu1; Xu, Lan-Ping1; Zhang, Xiao-Hui1; Wang, Yu1; Han, Wei1; Chen, Huan1; Wang, Feng-Rong1; Mo, Xiao-Dong1; Zhang, Yuan-Yuan1; Huo, Ming-Rui1; Zhao, Xiao-Su1; Kong, Y.1; Liu, Kai-Yan1; Huang, Xiao-Jun1,2,3
刊名JOURNAL OF HEMATOLOGY & ONCOLOGY
2015-07-10
DOI10.1186/s13045-015-0182-9
8
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology ; Hematology
研究领域[WOS]Oncology ; Hematology
关键词[WOS]STEM-CELL TRANSPLANTATION ; BONE-MARROW ; HLA ANTIBODIES ; CORD BLOOD ; PHASE-II ; HEMATOLOGIC MALIGNANCIES ; HIGH-RISK ; HOST-DISEASE ; FOLLOW-UP ; LEUKEMIA
英文摘要

Background: Small studies suggest an association of donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) with primary graft failure (GF) following haploidentical stem cell transplantation, but primary graft rejection (GR) was not discriminated from primary poor graft function (PGF). In this study, we aimed to determine the association of DSAs with primary GF, including GR and PGF, in patients who underwent unmanipulated haploidentical blood and marrow transplantation.

Methods: A total of 345 subjects were prospectively recruited and randomly selected as training group (n = 173) and validation group (n = 172). Patient plasma/serum was screened. For HLA antibody positive samples with a median fluorescent intensity (MFI) >500, DSAs were further tested using a LABScreen Single Antigen Kit (One Lambda).

Results: A total of 342 patients (99.1 %) achieved sustained myeloid engraftment. The median times to neutrophil engraftment and platelet engraftment were 13 days (range, 8-28 days) and 18 days (range, 6-330 days), respectively. The cumulative incidence of primary GF was 6.4 +/- 1.3 % and included GR (0.9 +/- 0.5 %) and PGF (5.5 +/- 1.2 %). Of the 345 cases tested, 39 (11.3 %) were DSA positive. Multivariate models showed that DSAs (MFI >= 10,000) were correlated to primary GR (P < 0.001) and that DSAs (MFI >= 2000) were strongly associated with primary PGF (P = 0.005). All patients were classified into three groups for analysis. Group A included cases that were DSA negative and those with a DSA MFI <2000 (n = 316), group B included cases with a 2000 <= MFI < 10,000 (n = 19), and group C included cases with a MFI >= 10,000 (n = 10). The DSAs were associated with an increased incidence of the primary GF (3.2 vs. 31.6 vs. 60 %, for groups A, B, and C, respectively, P < 0.001), transplant-related mortality (TRM) rate (17.2 vs. 14.7 vs. 33.3 %, for groups A, B, and C, respectively, P = 0.022), and inferior overall survival (OS, 77.3 vs. 85.3 vs. 44.4 %, for groups A, B, and C, respectively, P = 0.015). The primary GF was independently associated with a higher incidence of TRM (P < 0.001), inferior disease-free survival (P < 0.001), and OS (P < 0.001).

Conclusions: The findings confirmed the effect of DSAs on primary GF, including GR and PGF, and survival. Our results suggest incorporating DSAs in the algorithm for haploidentical donor selection.

语种英语
WOS记录号WOS:000357644200002
项目编号2013AA020401 ; 81230013 ; 2011-4022-08
资助机构National High Technology Research and Development Program of China (Program 863) ; Milstein Medical Asian American Partnership Foundation ; Key Program of National Natural Science Foundation of China ; Scientific Research Foundation for Capital Medicine Development
引用统计
被引频次:38[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/59477
专题北京大学第二临床医学院_血液科
医学人文研究院/公共教学部_哲学与社会科学系
作者单位1.Peking Univ, Peoples Hosp, Inst Hematol, Beijing Key Lab Hematopoiet Stem Cell Transplanta, Beijing 100044, Peoples R China
2.Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China
3.Peking Univ, Collaborat Innovat Ctr Hematol, Beijing 100044, Peoples R China
推荐引用方式
GB/T 7714
Chang, Ying-Jun,Zhao, Xiang-Yu,Xu, Lan-Ping,et al. Donor-specific anti-human leukocyte antigen antibodies were associated with primary graft failure after unmanipulated haploidentical blood and marrow transplantation: a prospective study with randomly assigned training and validation sets[J]. JOURNAL OF HEMATOLOGY &amp; ONCOLOGY,2015,8.
APA Chang, Ying-Jun.,Zhao, Xiang-Yu.,Xu, Lan-Ping.,Zhang, Xiao-Hui.,Wang, Yu.,...&Huang, Xiao-Jun.(2015).Donor-specific anti-human leukocyte antigen antibodies were associated with primary graft failure after unmanipulated haploidentical blood and marrow transplantation: a prospective study with randomly assigned training and validation sets.JOURNAL OF HEMATOLOGY & ONCOLOGY,8.
MLA Chang, Ying-Jun,et al."Donor-specific anti-human leukocyte antigen antibodies were associated with primary graft failure after unmanipulated haploidentical blood and marrow transplantation: a prospective study with randomly assigned training and validation sets".JOURNAL OF HEMATOLOGY & ONCOLOGY 8(2015).
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