Session: 732. Allogeneic Transplantation: Disease Response and Comparative Treatment Studies: Poster II
Hematology Disease Topics & Pathways:
Research, Clinical Research, patient-reported outcomes
To study the effect of HED among recipients of haplo HCT, we analyzed 322 consecutive recipient/donor pairs who received their transplant at our center with a median follow up of 57.2 months (range 18-196). HED was calculated as pairwise differences using two methods: a Grantham distance metric using a perl Script ( https://sourceforge.net/projects/granthamdist/) and manual calculation of one random sample from each analysis to verity results. Data were collected from our database where it was prospectively entered. Patient diagnosis included AML (n=122), ALL (n=68), MDS (n=41), NHL (n=50), other (n=41). Baseline recipient characteristics included a median age of 50 years (19,80), 53% white, HCT-CI≥3 in 50%, Disease risk (intermediate 53%, high/very high 33%), PBSC graft 80% and myeloablative conditioning 49%. Donor characteristics were median age 37 years (13,73), CMV positive 61%, male 61% and female donor to male recipient 21%. Pairwise divergence of HLA class I and class II showed differences in values with HLA-B, DRB1 and DQB1 contributing most to mean HED class I and II. The HED values for recipient included mean HLA class I 6.85 (HLA-A 7.08, B 8.24 and C 3.47), class II 8.58 (DRB1 10.97, DQB1 10.06 and DPB1 4.06). Donor mean HED HLA-class I was 6.5 (HLA-A 6.43, B7.93 and C 4.61), mean HLA-class II was 8.84 (DRB1 10.93, DQB1 11.24 and DPB1 4.06). The mean HEDs for the mismatched haplotype between donor and recipient were class I 6.49 (A 6.43, B 7.8, C4.94) and Class II 8.74 (DRB1 10.48, DQB1 10.06, DPB1 4.06). Next, we performed a univariate Cox model to identify HED variables that are associated with OS, DFS, NRM and relapse. Based on continuous and dichotomized divergence (median cutoff) univariate cox, a high HED in class I mismatched donor-recipient haplotype was significant for worse DFS (HR 1.11, p=0.020), and relapse (HR 1.11, p=0.02). Also, high HED in HLA B in mismatched haplotype was significant for worse OS (HR 1.07, p=0.02), DFS (HR 1.09, p=0.002), higher relapse (HR 1.10, p=0.003) and similar NRM to low HED. AS HLA-B was the biggest contributor to class I HED mean and the only predictor of outcomes in a univariate cox, we evaluated HLA-B in mismatched haplotype ( donor-recipient) further in a Multivariate analysis using dichotomization based on median level. Variables in the analysis included were age (<55, ≥55), gender, race, diagnosis, cell source, regimen intensity, HCT-CI (0-2, ≥3), DRI (low/intermediate, high/very high), CMV status; donor age (<38, ≥38), donor gender, female-donor-to-male-recipient, donor CMV status, year of transplant. The multivariate cox analysis showed that high HED (≥7.8 vs <7.8) was significant for worse DFS ( HR 1.53, 95% CI 1.09-2.16; p=0.01), higher relapse (HR 1.61, CI 1.07-2.44, p=0.024) and similar NRM and OS (table 1) . The significance was reproduced in the lymphoid and myeloid lineages. In Summary, among patients receiving haplo with PTCY, a high divergence in HLA-B mismatch haplotype increases relapse risk and worsens DFS. In addition to this being the first analysis to assess HED in a large haplo cohort, the negative consequences of HED can be mitigated by selecting donors with lower HED in the mismatched haplotype at HLA-B.
Disclosures: Solh: Partner Therapeutics: Research Funding; ADC Therapeutics: Research Funding.
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