Session: 722. Clinical Allogeneic Transplantation: Acute and Chronic GVHD, Immune Reconstitution: Poster I
Hematology Disease Topics & Pathways:
Leukemia, ALL, AML, Diseases, Non-Hodgkin Lymphoma, MDS, B-Cell Lymphoma, Technology and Procedures, Lymphoid Malignancies, Myeloid Malignancies, Clinically relevant, molecular testing
In present study, the influence of hematological and immunological hereditary predisposition genes on aGVHD after allo-HSCT in the patients with hematological malignancies was investigated.
Between February 2018 and August 2019, 92 patients with hematological malignancies who underwent allo-HSCT in Beijing Boren Hospital were enrolled. The median age was 17 (1 to 45) years old. The diagnoses included acute myeloid leukemia (37, 40.2%), acute lymphoblastic leukemia (36, 39.1%), non-Hodgkin's lymphoma (13, 14.1%), and myelodysplastic syndrome (6, 6.5%). The disease status before transplant was complete remission in 54 (58.7%), non-remission in 23 (25%), and relapse in 15 (16.3%). Before transplants, blood samples were collected from the patients, their parents and potential related donors to detect hematological and immunological hereditary predisposition genes with whole exon sequencing and validation by sanger sequencing. The donors were from identical siblings (4, 4.3%) or matched unrelated volunteers (8, 8.7%) or haploidentical family members (80, 86.9%). Myeloablative conditioning regimens with either total body irradiation/fludarabine-based or busulfan/fludarabine-based were applied. Anti-thymocyte globulin was used in haploidentical and unrelated transplants. GVHD prophylaxis was with cyclosporine, short-term methotrexate and mycophenolate mofetil. Methylprednisolong 1-2mg/kg daily was used for aGVHD treatment and basiliximab was administrated in severe aGVHD.
Forty-eight patients (52.2%) developed aGVHD as aGVHD group and 44 patients (47.8%) have no aGVHD as non-aGVHD group. IL7R gene heterozygous mutations in recipients significantly increased overall aGVHD and also severe aGVHD after allo-HSCT. IL7R gene heterozygous mutations were found in 7/48 patients in aGVHD group, but 0/44 in non-GVHD group (P = 0.041). The incidence of grade III-IV aGVHD in patients with IL7R gene heterozygous mutations was significantly higher than that without IL7R gene heterozygous mutations. (5/7 vs. 7/41, P=0.007). Among the patients with IL7R gene heterozygous mutations in aGVHD group, 5/7 patients (71.4%) had grade III-IV aGVHD. Three of them with grade III aGVHD had the same heterozygous mutation site: c.c1241t; p.t414m and rest 2 patients with grade IV aGVHD had the same heterozygous mutation site: c.g314a; p. S105n.
Our preliminary results have shown that IL7R gene heterozygous mutations in recipients have significantly increased the risk of overall aGVHD and severe aGVHD after allo-HSCT in the patients with hematological malignancies. Larger sample size is needed to address this issue.
Disclosures: No relevant conflicts of interest to declare.
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