TORNA ALL’ELENCO

Gvhd prophylaxis modulates the influence of HLA mismatches on the unshared haplotype on the outcomes after t-cell repleted haploidentical stem cell transplantation in HLA

2017
AOU Città della Salute di Torino

Tipo pubblicazione

Conference Abstract

Autori/Collaboratori (18)Vedi tutti...

Lorentino F

Labopin M

Fleischhauer K


et alii...

Abstract

Haploidentical hematopoietic stem cell transplantation (haplo- HSCT) with T-repleted grafts is an option for high risk acute leukemia patients (pts) who lack a matched donor, with GvHD prophylaxis mainly based on anti-thymocyte globulin (ATG) or post-transplant cyclophosphamide (PTCy). We aimed to evaluate if HaploSCT outcomes could be shaped by HLA mismatches (mm) on the unshared haplotype (UH) between pts and donors, possibly refining current criteria for donor selection. We included 509 pairs with HLA-A, -B, -C and -DRB1 typing at low (66%) or high (34%) resolution. A validated high-resolution imputation algorithm, developed by the German National Donor Registry, was used to impute allelelevel matching in 418 pairs. More than half of pts were in complete remission, and most transplants were performed with reduced intensity conditioning (52%). Stem cell source was peripheral blood (PB) for 61% of pts, bone marrow for 39%. ATG was used in 39% of cases, PTCy in 61%. In multivariate analysis (including center effect, pts age, donor gender, diagnosis, disease status, conditioning intensity, stem cells source) an antigenic but not an allelic mm at the DRB1 locus was an independent risk factor for aGvHD ?2 in PTCy (HR 2.0; 95% CI 1.2-4.0, p=0.02) but not in ATG regimens. Neither mm at any HLA locus nor predicted NK alloreactivity based on KIR ligand mm in the GvL vector influenced transplant-related mortality, relapse and disease-free survival. The influence of clinical variables on aGvHD was modulated by the adopted GvHD prophylaxis: PB as stem cell source, myeloablative conditioning and female donors were independently associated with the hazards of aGvHD in PTCy (HR 2.2, 95% CI 1.4-3, p<0.01; HR 1.7, 95% CI 1.1-2.5, p=0.04; HR 1.8, 95% CI 1-3.2, p=0.05, respectively) but not in ATG regimens. Our data suggest that HLA mm on the UH do not appear to be of prominent importance for haplo-donor selection. However, its role and other factors influencing alloreactiv

DOI : 10.1111/tan.13034

Keywords

multivariate analysis; mortality; male; human; haplotype; gender; female; donor selection; disease free survival; diagnosis; clinical study; bone marrow; alloimmunity; acute graft versus host disease; thymocyte antibody; ligand; HLA A antigen; endogenous compound; cyclophosphamide; myeloablative conditioning; prophylaxis; reduced intensity conditioning; register; relapse; remission; risk factor; stem cell transplantation; T lymphocyte;