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学科主题: 临床医学
题名:
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
作者: 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
发表日期: 2015-07-10
DOI: 10.1186/s13045-015-0182-9
卷: 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
所属项目编号: 2013AA020401 ; 81230013 ; 2011-4022-08
项目资助者: 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
WOS记录号: WOS:000357644200002
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内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/59477
Appears in Collections:北京大学第二临床医学院_血液科_期刊论文

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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

Recommended Citation:
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.
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