Session: 722. Allogeneic Transplantation: Acute and Chronic GVHD and Immune Reconstitution: Poster III
Hematology Disease Topics & Pathways:
Research, Clinical trials, Adult, Clinical Research, Patient-reported outcomes, Registries, Study Population, Human
To that end,
we studied 322 consecutive recipient/donor pairs who received HIDT with PTCY at our center between 2005-2020 with a median follow up of 57.2 months. In addition to HLA-DPB1 matching and vector, we calculated HED using the GRAHAM distance score within the recipient HLA-DPB1 loci. HLA-DPB1 mismatch vector was bidirectional (n=167), graft vs host (GVH only, n=49), host vs graft (HVG only, n=39) and matched (n=67). The median HED score in the HLA-DPB1 recipient was 4.06 (range 0-10.68). Recipients were grouped into 4 different cohort based on the direction of HLA-DPB1 mismatch and the HED score (high >4.06 vs low): matched (n=67), HLA-DPB1 mismatched GVH/bidirectional low divergence (n=104), HLA-DPB1 mismatched GVH/bidirectional high divergence (n=112) and HLA-DPB1 mismatch HVG (n=39).
Patient’s characteristics were median age 49.5 (19,80) years, male sex 58%, disease ( AML 38%, ALL 21%, MDS 12%, NHL 10%, other 19%); Cell source (PBSC 80%); regimen intensity ( myeloablative 49%); HCT-CI comorbidity index ≥3 in 50%; disease risk ( high/very high 35%); donor male sex 61% and female donor to male recipient (21%). Donor was a child, sibling/half sibling or parent in 47%, 38% and 14% respectively. In univariate analysis, high HED score in recipient HLA-DPB1 had no impact on OS, DFS, Relapse or NRM but was significant for all grade ( HR 2.10, p=0.005) and moderate-severe (HR 1.86, p=0.04) cGVHD compared to patients with low HED score. A subgroup analysis comparing cGVHD cumulative incidences based on vector and divergence score showed that HLA-DPB1 MM in GVH/bidirectional with high HED had higher all grade and moderate-severe cGHVD compared to matched recipients (P=0.01 and 0.004). Additionally, patients with HLA-DPB1 MM in GVH/bidirectional high HED score had higher all grade and moderate-severe cGVHD compared to MM in GVH/bidirectional with low HED score (p=0.005 and 0.013)
A multivariable analysis using cox model was performed on moderate-severe cGVHD and showed that in addition to black race and being transplanted in earlier years ( 2005-2013 vs later), patients with HLA-DPB1 mismatched in GVH/bidirectional with high divergence score had higher risk of mod-severe cGVHD ( HR 2.20, CI 1.09-4.43, p=0.028) than matched HLA-DPB1. Similarly, patients with HLA-DPB1 MM in the HVG direction had higher risk of mod-severe cGVHD compared to matched (HR 2.57, CI 1.15-5.74, p=0.002).
In conclusion, our analysis shows that in the context of PTCY-based HIDT, recipient with more divergent HLA-DPB1 alleles are at significantly higher risk of moderate-to-severe chronic GVHD when a HLA-DPB1 mismatch is present in the GVH/bidirectional direction, a result predicted by the divergent allele advantage hypothesis. Furthermore, the presence of an HLA-DPB1 mismatch in the HVG-only direction also resulted in more chronic GVHD, a finding requiring further mechanistic study. In recipients with more divergent HLA-DPB1 alleles by HED scoring, care will need to be taken in donor selection to balance the detrimental effects of HLA-DPB1 mismatch on chronic GVHD with the known beneficial effects of a TCE non-permissive HLA-DPB1 mismatch in terms of relapse reduction.
Disclosures: Solh: Sanofi: Consultancy; GlaxoSmithKline: Speakers Bureau; Bristol Myers Squibb: Consultancy, Speakers Bureau.