Allogeneic Stem Cell Transplantation From Unrelated One-Antigen HLA-Mismatched Donor, Increases Acute II-IV Gvhd Incidence without Interfering with Other Post-Transplant Complications
Authors: De Berranger Eva , Terriou Louis , Coiteux Valérie , Magro Leonardo , Dufossé Françoise , Jouet Jean-Pierre , Yakoub-Agha Ibrahim 
Published: October 2019

Abstract
Abstract 2378
Allogeneic stem cell transplantation (allo-SCT) offers potential curative treatment of for a wide range of otherwise fatal hematological diseases. However, only one third of patients have an HLA-identical sibling donor. We have previously reported that in patients with standard risk malignancy, transplantation from unrelated HLA-allellically matched donors (10/10) led to outcomes similar to those from HLA-identical sibling donors (Yakoub-Agha et al, JCO 2006). Indeed, with the increase in the number of single-child families, stem cell grafts from unrelated donors are being increasingly used and more than 30% of patients eligible for allo-CST, are still lacking a well-matched donor. In the attempt to investigate the impact of unrelated one-antigen HLA-mismatched graft, we report a single center retrospective study on 209 patients who underwent allo-CST from identical HLA-sibling donor (n=123), unrelated HLA-matched donor (10/10) (n=73) and unrelated one-antigen-HLA-mismatched donor (9/10) (n=13) over the last 5 years. In order to homogenize our cohort, patients with CML, aplastic anemia or lymphoproliferative disorder were excluded from the study. Therefore, underlying diseases were AML (n=104), ALL (n=54), myelodysplastic syndrome (n=30), and myeloproliferative syndrome (n=21). Of the 117 (56%) males patients, 49 (23%) received graft from female donor (classical sex-mismatch). Medians age of recipients and donors at transplantation were 45.2 years (4.4-65.5) and 40.8 years (2.0-67.5), respectively. Patients received conditioning regimens using either myeloablative (n=149) including 81 who received High-dose TBI (12Gy) or nonmyeloablative (n=60) including 48 who received low-dose TBI (2Gy). Antithymoglobulin was given to 25 pts. Bone marrow was the main source of stem cells (n=150; 72%).

Results:
with the median of follow-up of 37.9 months, 78 patients died including 25 from TRM. Relapse was recorded in 70 patients. Seventy-two patients experienced acute GVHD (aGVHD) including 47 with II-IV grades and 30 with III-IV grades. In multivariate analyses, donor type (unrelated regardless the degree of HLA-matching vs related) and conditioning (nonmyeloablative vs myeloablative) were the most important risk factors negatively influencing the overall survival [p=.002; HR=2.038 and p=.016; HR=1.81, respectively) and event-free survival (p=.005; HR=1.783 and p=.015; HR=1.728, respectively). As expected, the only factor that influenced the risk of relapse was the conditioning type (nonmyeloablative vs myeloablative) (p=.048; HR=1.699) while donor type was found to influence TRM (p=.030; HR=2.428). Graft from unrelated one-antigen HLA-mismatched donor (9/10) was the foremost risk factor for acute grade II-IV GVHD (p=.019; HR=2.663; [95%CI: 1.178–6.019]).
In conclusion, except for acute II-IV GHVD, allo-CST from unrelated one-antigen HLA-mismatched donor (9/10), seemed to led to outcomes similar to those from HLA-identical unrelated donor (10/10) and may be considered as an alternative option for patients without a full-matched donor. Prospective studies are warranted, however, to confirm our data in larger cohort of patients.

Disclosures:
No relevant conflicts of interest to declare.