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

• Published in: Journal of hematology and oncology Vol. 8; no. 1; p. 84
• Main Authors: Chang, Ying-Jun, Zhao, Xiang-Yu, Xu, Lan-Ping, Zhang, Xiao-Hui, Wang, Yu, Han, Wei, Chen, Huan, Wang, Feng-Rong, Mo, Xiao-Dong, Zhang, Yuan-Yuan, Huo, Ming-Rui, Zhao, Xiao-Su, Y, Kong, Liu, Kai-Yan, Huang, Xiao-Jun
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 10.07.2015; BioMed Central
• Subjects: Adolescent; Adult; Analysis; Antibodies; Antigens; Blood platelets; Bone marrow; Bone Marrow Transplantation - methods; Child; Child, Preschool; Cohort Studies; Female; Graft versus host disease; Health aspects; Hematology; Hematopoietic Stem Cell Transplantation - methods; Histocompatibility antigens; HLA Antigens - immunology; HLA histocompatibility antigens; Humans; Leukocytes; Male; Middle Aged; Mortality; Neutrophils; Oncology; Patients; Prognosis; Prospective Studies; Stem cell transplantation; Stem cells; Tissue Donors; Transplantation; Transplantation Conditioning - methods; Transplantation, Homologous - methods; Treatment Outcome; Viral antibodies; Young Adult
• DOI: 10.1186/s13045-015-0182-9
• ISSN: 1756-8722

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. 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). 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 ± .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). 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.