Donor-specific antibodies and primary graft failure in allo-hematopoietic stem cell transplant: a systematic review and meta-analysis: DSA and primary graft failure in allo-HSCT.

Abstract

BACKGROUND\nWith increase in the number of non-matched hematopoietic stem cell transplants (HSCT), there has been growth in evidence regarding factors affecting graft outcomes. One of the factors affecting graft outcomes that are currently being evaluated is anti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs).\n\n\nOBJECTIVE\nWe designed our study to analyze the clinical relevance of anti-HLA DSAs in patients who have undergone hematopoietic stem cell transplant at a population level by conducting a systematic review of existing literature.\n\n\nSTUDY DESIGN\nA comprehensive search was conducted through PUBMED, Embase, Cochrane library and Web of Science from inception to January 1, 2021. A meta-analysis was performed of the association between anti-HLA DSAs and primary graft failure with further subgroup analyses. It was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.\n\n\nRESULTS\nA total of 920 eligible citations were identified out of which 15 studies were included in the final meta-analyses after application of rigorous selection criteria and independent review. A total of 2436 patients were included. Patients with anti-HLA DSAs prior to HSCT had a 7.47-fold increased risk of primary graft failure compared to patients without DSA (OR 7.47, 95%CI 4.54-12.28, p<0.001; I2= 28.91%, P\u202f=\u202f0.1315). In subgroup and meta-regression analyses, areas, NOS, mean fluorescence intensity (MFI) cut off, primary diseases, HSCT types, graft sources, and pre-transplant desensitization did not affect the impact of anti-HLA DSAs on primary graft failure (PGF). There was no significant difference between the impact of HLA class I and II on PGF as well.\n\n\nCONCLUSION\nWe conclude that prior presence of anti-HLA DSAs had negative impact on graft outcomes in patients with haploidentical and umbilical cord blood hematopoietic stem cell transplants.