title: Donors with HLA-B*58:01/TNFα − 308A haplotype are unfavorable to haploidentical hematopoietic stem cell transplantation in acute lymphoblastic leukemia.
abstract: We investigated the clinical characteristics of acute lymphoblastic leukemia (ALL) patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) using haploidentical donors carrying HLA-B*58:01/TNFα − 308A (B*58:01-TNF2) haplotype. A total of 136 B-ALL and 29T/NK-ALL cases were recruited. DNA samples from the patients and their family members were assayed for HLA typing and genotyping of TNFα -308 (rs1800629). The B*58:01-TNF2 haplotype in related donors was determined by their family relationships. Outcomes within 2 years, disease course, and complications within 100 days were compared among patients using haploidentical donors carrying B*58:01-TNF2 haplotype (21 cases), those using haploidentical donors without B*58:01-TNF2 haplotype (100 cases), and those using HLA-identical sibling donors with or without B*58:01-TNF2 haplotype (44 cases). Compared with the other two groups, patients using haploidentical donors carrying B*58:01-TNF2 haplotype had higher overall mortality (adjusted P = 0.039) and non-relapse mortality (adjusted P = 0.001) within 2 years, delayed platelet engraftment (adjusted P < 0.0001), higher incidences of severe acute graft-versus-host disease (aGVHD) (P = 0.007), severe late-onset hemorrhagic cystitis (P = 0.002), blood stream infection (P = 0.017), and invasive fungal disease (P = 0.004) within 100 days. Therefore, donors carrying the B*58:01-TNF2 haplotype may cause more serious complications and poorer outcomes to ALL recipients.
authors.affiliation: Department of Hematology, Peking University First Hospital, China.
authors.forename: Liyun
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Hematology, Peking University First Hospital, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Chen
authors.affiliation: Ludaopei Hematology and Oncology Center, Hebei Yanda Hospital, China.
authors.forename: Hongxing
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Pediatrics, Zunyi Medical College Affiliated Hospital, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department Of Laboratory Medicine, General Hospital of Armed Police, China.
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Central Laboratory, Peking University First Hospital, China.
authors.forename: Dingfang
authors.initials: D
authors.lastname: Bu
authors.affiliation: Department of Hematology, Peking University First Hospital, China. Electronic address: zhuping@bjmu.edu.cn.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhu
mesh_terms: D000293:Adolescent; D000328:Adult; D064591:Allografts; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology / Q000401:mortality; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology; D006239:Haplotypes / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000473:pathology; D035781:Siblings; D015996:Survival Rate; D014019:Tissue Donors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
chemical_list: D015235:HLA-B Antigens; C500126:HLA-B*58:01 antigen; D014409:Tumor Necrosis Factor-alpha
keywords: Acute lymphoblastic leukemia; HLA-B*58:01/TNFα −308A (B*58:01-TNF2) haplotype; Haploidentical allergenic hematopoietic stem cell transplantation