denotes an abstract that is clinically relevant.
denotes that this is a recommended PHD Trainee Session.
denotes that this is a ticketed session.Session: 723. Allogeneic Transplantation: Long-term Follow-up, Complications, and Disease Recurrence: Poster III
Hematology Disease Topics & Pathways:
AML, Diseases, Lymphoid Malignancies, Myeloid Malignancies, Measurable Residual Disease
Objective: In current study, the influence of somatic and germline gene variants on the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with hematological malignancies was studied.
Methods: Between October 2017 and April 2024, we retrospectively enrolled 797 patients with hematological malignancies who underwent allo-HSCT in our hospital. The median age was 17.84 years (range: 0.33-71.4 years). Diagnosis included B-ALL (39.6%), B-NHL (3.6%), T-ALL (7.5%), T-LBL/ALL (6.4% s), AML (29.0%), MDS (2.6%) and others. Total 491 patients had relapsed history, and 201 cases had received allo-HSCT before. Four hundred and seventy-two patients achieved complete remission before transplants. The types of transplants were haploidentical (68.9%), identical siblings (9.3%) and unrelated (21.8%). 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. Graft-versus-host disease (GVHD) prophylaxis was with cyclosporine, short-term methotrexate and mycophenolate mofetil. Total 408 patients were analyzed for somatic gene variants. Bone marrow or tissue samples at diagnosis or relapse were detected for 339 kinds of somatic gene variants by Illumina next generation sequencing (NGS). Total 558 patients were analyzed for germline gene variants before transplant. Genomic DNA was extracted from blood (patients, parents) and tested using NGS. More than 900 germline susceptibility gene variants were screened.
Results: Median follow-up was 34.5 months (range: 0.59-80.4 months). The three-year overall survival (OS) was 66.1%. Three-year cumulative incidence of relapse (CIR) was 29.9%. Three-year non-relapse mortality (NRM) was 11.1%. The top five somatic gene variants were TP53 (14.5%), NRAS (14.2%), PTPN11 (9.8%), KRAS (9.1%) and KMT2D (7.1%). The top five germline gene variants were BTLA (15.6%), TNFAIP3 (14%), MPEG1 (12.7%), EP300 (11.8%), MLH1 (9.0%). Somatic TP53, IKZF1 and GATA2 gene variants, and germline POLD1 and G6PD gene variants were all risk factors for HSCT outcomes. Somatic TP53 gene variants were significantly associated with relapse and death after HSCT (TP53-MUT, n = 59; OS: HR = 2.5, p < 0.0001; Relapse: HR = 2.8, p < 0.0001). Somatic IKZF1 gene variants were significantly associated with post-transplant death (IKZF1-MUT, n = 14; OS: HR = 2.2, p = 0.021; Relapse: HR = 2, p = 0.082). Somatic GATA2 gene variants were risk factor for recurrence and death (GATA2-MUT, n = 7; OS: HR = 3.4, p = 0.0032; Relapse: HR = 3.4, p = 0.0017). Germline POLD1 gene variants were significant risk factors for OS and recurrence (POLD1-MUT, n = 10; OS: HR = 2.6, p = 0.019; Relapse: HR = 2.4, p = 0.033). Germline G6PD gene variants were significant risk factor for recurrence (G6PD-MUT, n = 8; OS: HR = 2.1, p = 0.094; Relapse: HR = 3.3, p = 0.0067). On this basis, a multivariate cox regression analysis was conducted. After adjusting for age and disease type, somatic TP53 and GATA2 gene variants were still observed as significant independent prognostic factors for OS, and there was a trend for germline POLD1 gene variants increased the risk of death (somatic TP53: HR = 2.90, p < 0.0001; somatic GATA2: HR = 2.92, p = 0.017; germline POLD1: HR = 2.62, p = 0.085; Global p = 0.0003, C-index = 0.69).
Conclusions: Our study has demonstrated that both somatic and germline gene variants could have impact on the outcomes of allo-HSCT in patients with hematological malignancies. Somatic TP53, IKZF1, and GATA2 gene variants and germline POLD1 and G6PD gene variants were associated with poorer prognosis post-HSCT. Somatic TP53 and GATA2 gene variants were independent risk factors for OS after transplant.
Disclosures: No relevant conflicts of interest to declare.