Grafts From HLA-Identical Siblings Versus HLA-Allelic-Matched Unrelated Donors (10/10) In Patients Undergoing Allogeneic Stem Cell Transplantation Following Reduced-Intensity Conditioning Regimen
Authors: De Berranger Eva , Wemeau Mathieu , Herbaux Charles , Pascale Cracco , Jouet Jean-Pierre , Yakoub-Agha Ibrahim 
Published: October 2019

Abstract
Abstract 2380
Nonmyeloablative, or reduced-intensity conditioning (RIC), regimens before allo-SCT have emerged as an attractive modality to decrease transplant-related toxicity while preserving the graft-versus-tumor effect. However, as for standard myeloablative allo-CST, only one third of patients have an HLA-identical sibling donor. Indeed, with the increase in the number of single-child families, stem cell grafts from unrelated donors are being increasingly used.
We have previously reported, that in patients with standard-risk malignancy undergoing allo-SCT with CPM and TBI as conditioning treatment, unmodified marrow as a source of graft, and Cs-A plus short-course MTX as GVHD prophylaxis, there were no significant differences between the outcomes of patients receiving graft from siblings and those from unrelated fully HLA-matched donors (Yakoub-Agha et al, JCO 2006). However, no conclusions can be drawn with certainty concerning patients with more advanced disease, those who received a peripheral blood graft or especially those with a non-myeloablative conditioning regimen.
Here we report a retrospective study of 58 consecutive patients who received RIC allo-CST. Donors were HLA-identical sibling (n=35) and unrelated molecularly HLA-identical donor.
All donor/recipient pairs were typed at the allelic level. They were first typed at 2-digit level for HLA class I (HLA-A, B and Cw) and class II (HLA-DRB1 and DQB1) using published HLA class I PCR-SSO and/or SSP typing protocols. For unrelated donors, HLA-A, B, Cw, DRB1, B3, B4, B5 and DQB1 subtyping was performed using different PCR-SSP kits. HLA typing was performed according to the current use of the EFI Histocompatibility Laboratory standards. Only donor/recipient unrelated pairs matched for both alleles were included in this study.
Diagnosis were AML (n=27), ALL (n=3), myelodysplastic syndrome (n=13), and myeloproliferative syndrome (n=15). Of the 32 (55%) males patients, 14 (43%) received graft from female donor (classical sex-mismatch). Medians age of recipients and donors at transplantation were 58 years (41.3-65.5) and 47.1 years (22.2-67.5), respectively. Patients received either low-dose TBI (2Gy) (n=46) or Busulfan-based (n=12) conditioning regimen. Antithymoglobulin was given to 12 patients. As usual in RIC setting, Peripheral Blood Stem Cells was the main source of graft (n=38; 65%), otherwise marrow graft (n=20).

Results:
with the median of follow-up of 27.2 months (range, 8.1–79.4), 24 patients died including 9 from TRM. Relapse was recorded in 21 patients. Eighteen patients experienced acute GVHD (aGVHD) including 12 with II-IV grades and 7 with III-IV grades. Contrary to what we have previously reported in myeloablative allo-CST sittings, patients who underwent RIC and received graft from unrelated HLA-matched (10/10) donor, experienced worse outcomes compared to those transplanted with an HLA-identical sibling. Indeed, in multivariate analyses, donor type (unrelated HLA-matched 10/10 vs HLA-identical sibling) was the most important risk factors negatively influenced the overall survival and EFS [p=.01; HR=3.068; [95%CI: 1.312–7.174]) and (p=.050; HR=2.081; [95%CI: 1.001–4.347]), respectively.
To our knowledge, this is the first study which compares results of sibling transplantation to HLA-allellically-matched (10/10) unrelated transplantation. Even though, results of the latter did not compare favorably to those obtained with an HLA-identical sibling donors, grafts from HLA-matched unrelated donors, are still an attractive option especially for patients with high-risk malignancy. Our data emphasis the need of prospective studies evaluating factors influencing outcomes of HLA-allellically-matched (10/10) unrelated transplantations.

Disclosures:
No relevant conflicts of interest to declare.