Impact of HLA Allele Mismatch on the Outcome of Patients with Reduced-Intensity Allogeneic Haematopoietic Stem Cell Transplantation from Unrelated Donors: Analysis of 103 Patients of the French Registry.

Reduced-intensity conditioning regimens (RIC) had become a classical strategy of allogeneic hematopoietic stem cell transplantation (HSCT) and many patients are now transplanted with unrelated donor. The aim of this restrospective study was to evaluate the impact of HLA mismatches between donor (D) and recipient (R) at the allelic level on survival after RIC. We analyzed 103 patients registered in France from Jan 1999 to Dec 2003 with a median age of 46 years (18–67). All patients had hematologic malignancies: AL (n=35), MM (n=18), CLL (n=5), NHL (n=11), HD (n=9), CML (n=12), MDS (n=9), and MPS (n=4). 39% of the patients were in an advanced phase of the disease at time of HSCT. Anti-thymocytes globulins (ATG) were part of the conditioning regimen for 77% of patients. The main source of stem cells was PBSC (n=65). Seventy-one D/R pairs (69%) were 10/10 HLA match at the allelic level. Mismatches concerned 5, 6, 15, 2 and 7 D/R pairs for HLA-A, -B, -C, -DRB1 and -DQB1, respectively. The results showed that 96% of patients engrafted. Acute GVHD grade II to IV and grade III/IV occurred in 46% and 19% of patients, respectively. The risk of developing cGvHD was 45% at 2 years. Overall survival (OS) was 42% at five years. Among the 47 patients alive, the median disease free survival (DFS) was 28 months. Among non-HLA parameters studied, the only factor associated with a good OS was the diagnosis of lymphoid disease (HD or NHL or CLL) (p=0.003). Recipient age <46y was only associated with less acute GvHD grade II to IV (p=0.008). Among HLA mismatches, we found that HLA-A and/or -B allelic mismatches had a negative impact on OS (p=0.006), DFS (p=0.006), acute GvHD grade II to IV (p=0.05). On the other hand, HLA-C or -DQB1 mismatches did not impact on OS, DFS, acute or chronic GvHD. We could not analyze DRB1 mismatch since there was only 2 patients reported. In conclusion, HSCT following RIC, with match or mismatch unrelated donors, is a feasible approach with best results observed for patients with lymphoid malignancies (NHL, CLL or HD). Among allelic HLA mismatches, HLA-A and/or -B seemed to be deleterious as compared to HLA-C or DQB1. These results help to identify most suitable donors and patients who are likely to benefit from RIC with unrelated donors when there is not a fully HLA match donor available.