Is the Use of 9/10 HLA Unrelated Donors Still Acceptable in Allogeneic Hematopoietic Stem Cell Transplantation for Hematological Malignancies? Comparison with Transplants From 10/10 HLA Unrelated Donors and Siblings
Authors: Michallet Mauricette , Sobh Mohamad , Morisset Stephane , Detrait Marie Y. , Labussiere Helene , Ducastelle Sophie , Barraco Fiorenza , Fattoum Jihane , Chelghoum Youcef , Thomas Xavier , Nicolini Franck E. 
Published: October 2019

Abstract
Abstract 3087

Introduction
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents the only potential to cure wide types of hematological diseases. A patient has 30% of chance to find a HLA-identical sibling donor while the rest of patients should find an alternative unrelated donor. The use of 10/10 HLA matched unrelated transplants has been used as a main alternative and with its unavailability, when available, a 9/10 HLA mismatched unrelated transplant has been used. The outcome of this last mismatched transplant is not very clear and its use according to patient and disease conditions has not been well defined yet.

Aims
To evaluate the outcome of allo-HSCT from 9/10 HLA mismatched unrelated donors compared to those from 10/10 HLA identical unrelated donors and siblings; and to define which category of patients can benefit the more in each alternative.

Material and methods
We have retrospectively studied the outcome of 213 patients who received allo-HSCT for different hematological malignancies, 121 (57%) from HLA identical siblings, 63 (29%) from 10/10 HLA identical unrelated donors and 29 (14%) from 9/10 HLA mismatched unrelated donors treated during the same period of time between 2006 and 2011 at our institution. In the mismatched group, 12 patients had the mismatch at HLA-A locus, 7 at the HLA-B, 7 at the HLA-C and 3 at the HLA-DQ. Characteristics between the 3 groups were comparable except for: disease type between the 2 unrelated groups, sex-matching, CMV-matching and ABO-matching. The different characteristics are detailed in Table 1.

Results
After HSCT, engraftment was significantly lower in the 9/10 HLA group (90%) than in the 10/10 HLA group (95%) than in the sibling group (99%), (p=0.03); the cumulative incidence of acute GVHD ≥2 at 3 months was 32% (23–41), 20% (15–26) and 27% (23–32) respectively; the cumulative incidence of extensive chronic GVHD at one year was 21% (13–30), 9% (5–13) and 17% (14–21) for the 3 groups respectively. After a median follow-up of 8 months (0–54) in the 9/10 HLA group, 10 months (0–60) in the 10/10 HLA group and 18 months in the siblings group, the median overall survival (OS) was 10 months (5–21), 18 months (11-NR) and 60 months (31-NR) respectively with a 2-years probability of 19% (8–44), 43% (31–59) and 63% (54–74) respectively. There was a higher but not significant relapse incidence at one year in the 9/10 HLA group compared to other groups while the transplant related mortality was significantly higher with a cumulative incidence at 1 year of 45% (35–55), (p<0.001) (Table1-results). In multivariate analysis, OS was negatively affected by unrelated donors [9/10 HR=5 (2.7–10), p=0.0001; 10/10 HR=2 (1.2–4), p=0.01], female donors [HR=2 (1.4–4), p=0.03] and disease status < CR1 or <chronic phase (CP) 1 [HR=3 (1.4–6), p=0.003]; while the TRM was negatively affected by unrelated donors [9/10 HR=9 (4–20), p<0.001; 10/10 HR=4 (1.2–10), p=0.03], female donors [HR=3 (1.2–7); p=0.01] and ABO minor incompatibility [HR=2.5 (1.2–5), p=0.01]. The funnel plot showing the adjusted TRM according to all covariates and comparing to the global population death rate, shows that the 9/10 HLA group has the worse TRM independently of any other factor.

Conclusion
We showed that allo-HSCT from 9/10 HLA mismatched unrelated donors have a significantly worse OS than those from matched unrelated donors and siblings; this was mainly due to an increased TRM in this group. Patients in first CR or CP could benefit the more from matched or 9/10 unrelated allo-HSCT while the use of transplants from 9/10 HLA unrelated donors in patients not in CR1 or CP1 should be limited to clinical trials. In view of these results, we should consider and evaluate the use of cord blood as an alternative source of transplant according to patient and disease conditions.

Disclosures:
No relevant conflicts of interest to declare.