Authors:
S. Ducreux (LYON, FR)
V. Dubois (LYON, FR)
P. Loiseau (Paris, FR)
I. Yakoub-Agha (Lille, FR)
M. Labalette (Lille, FR)
M. Michallet (LYON, FR)
M. Rubio (NANCY, FR)
A. Kennel (NANCY, FR)
N. Milpied (Bordeaux, FR)
X. Lafarge (BORDEAUX, FR)
J. Cahn (GRENOBLE, FR)
D. Masson (La Tronche, FR)
E. Daguindau (BESANCON, FR)
A. Dormoy (BESANCON, FR)
N. Maillard (POITIERS, FR)
I. Jollet (POITIERS, FR)
P. Chevallier (NANTES, FR)
A. Cesbron (FR)
J. Bay (CLERMONT FERRAND, FR)
F. Quainon (CLERMONT FERRAND, FR)
K. Amokrane (PARIS, FR)
F. Garnier (SAINT DENIS, FR)
G. Socie (PARIS, FR)
R. Porcher (PARIS, FR)
R. Peffault de la Tour (PARIS, FR)
Matching for HLA-A, -B, -C, –DRB1 loci (8/8 match) is associated with the highest overall survival (OS) rates after unrelated donor (URD) hematopoietic stem cell transplantation (HSCT). A detrimental role of additional HLA-DQB1, HLA-DPB1 and HLA-DRB3/4/5 mismatches (MM) has been recently identified on OS. We investigated the impact of HLA-DPB1 and HLA-DRB3/4/5 MM on outcomes in a large cohort of 10/10 matched URD HSCTs. 2,393 patients who received an initial HSCT from a 10/10 matched URD in 35 French centers were included between January 2000 and October 2012. High-resolution typing was performed for HLA-A, -B, -C, -DRB1, -DQB1, -DPB1 and -DRB3/4/5 loci for all donor/recipient pairs. Clinical data were obtained through ProMISe. Patients were classified into 5 different groups according to their global matching level for the 7 considered loci (10/14 to 14/14). HLA-DPB1 MM were classified as permissive or non-permissive. The primary composite endpoint for the analysis was GvH disease (GvHD)-free and relapse-free survival (GRFS). Acute GvHD (aGvHD), chronic GvHD, relapse and OS were also studied. The median follow-up was 59 months. Compared to 14/14 pairs, a significantly lower early GRFS (within 3 months after HSCT) was observed for patients who received a 10-11/14 (Hazard Ratio (HR) 2.0, 95% CI 1.4 to 2.9, p=0.0003) or a 12/14 URD HSCT (HR 1.4, 95% CI 1.1 to 1.8, p=0.01). This was related to an increased risk of grade III-IV aGvHD associated with 10-11/14 (HR 2.3, 95% CI 1.5 to 3.7, p=0.0004) and 12/14 pairs (HR 1.7, 95% CI 1.2 to 2.4, p=0.003). 10-11/14 pairs were also associated with a higher risk of death at 3 months (HR 2, 95% CI 1.1 to 3.6, p=0.024). In patients matched for HLA-DRB3/4/5 but MM for HLA-DPB1 (n=1846, 77.1%), two HLA-DPB1 MM and non-permissive HLA-DPB1 MM were associated with a lower early GRFS (HR 1.4, 95% CI 1.1 to 1.9, p=0.01 and HR 1.3, 95% CI 1.0 to 1.7, p=0.02 respectively) due to an increased risk of aGvHD (HR 1.7, 95% CI 1.2 to 2.5, p=0.002 and HR 1.50, 95% CI 1.08 to 2.08, p= 0.017 respectively). Only 19 pairs (0.8%) were DPB1 matched and DRB3/4/5 mismatched; HLA-DRB3/4/5 MM could thus not be analyzed. Multiple HLA-DPB1 and HLA-DRB3/4/5 MM have an early impact after 10/10 matched URDs HSCT. Prospective evaluation of matching for HLA-DPB1 and HLA-DRB3/4/5 is warranted to reduce early post-HSCT toxicity in donor-recipient 10/10 matched pairs.