1. Monitoring of post-transplant MLL-PTD as minimal residual disease can predict relapse after allogeneic HSCT in patients with acute myeloid leukemia and myelodysplastic syndrome.
- Author
-
Kong J, Gao MG, Qin YZ, Wang Y, Yan CH, Sun YQ, Chang YJ, Xu LP, Zhang XH, Liu KY, Huang XJ, and Zhao XS
- Subjects
- Disease-Free Survival, Female, Follow-Up Studies, Gene Rearrangement genetics, Hematopoietic Stem Cell Transplantation, Humans, Leukemia, Myeloid, Acute mortality, Leukemia, Myeloid, Acute surgery, Male, Middle Aged, Myelodysplastic Syndromes mortality, Myelodysplastic Syndromes surgery, Neoplasm Recurrence, Local mortality, Neoplasm, Residual, Postoperative Period, Predictive Value of Tests, Prognosis, Progression-Free Survival, Recurrence, Retrospective Studies, Transplantation, Homologous, Tumor Burden genetics, Histone-Lysine N-Methyltransferase genetics, Leukemia, Myeloid, Acute genetics, Myelodysplastic Syndromes genetics, Myeloid-Lymphoid Leukemia Protein genetics, Neoplasm Recurrence, Local genetics, Oncogene Proteins, Fusion genetics
- Abstract
Background: The mixed-lineage leukemia (MLL) gene is located on chromosome 11q23. The MLL gene can be rearranged to generate partial tandem duplications (MLL-PTD), which occurs in about 5-10% of acute myeloid leukemia (AML) with a normal karyotype and in 5-6% of myelodysplastic syndrome (MDS) patients. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently one of the curative therapies available for AML and MDS with excess blasts (MDS-EB). However, how the prognosis of patients with high levels of MLL-PTD after allo-HSCT, and whether MLL-PTD could be used as a reliable indicator for minimal residual disease (MRD) monitoring in transplant patients remains unknown. Our study purposed to analyze the dynamic changes of MLL-PTD peri-transplantation and the best threshold for predicting relapse after transplantation., Methods: We retrospectively collected the clinical data of 48 patients with MLL-PTD AML or MDS-EB who underwent allo-HSCT in Peking University People's Hospital. The MLL-PTD was examined by real-time quantitative polymerase chain reaction (RQ-PCR) at the diagnosis, before transplantation and the fixed time points after transplantation. Detectable MLL-PTD/ABL > 0.08% was defined as MLL-PTD positive in this study., Results: The 48 patients included 33 AML patients and 15 MDS-EB patients. The median follow-up time was 26(0.7-56) months after HSCT. In AML patients, 7 patients (21.2%) died of treatment-related mortality (TRM), 6 patients (18.2%) underwent hematological relapse and died ultimately. Of the 15 patients with MDS-EB, 2 patients (13.3%) died of infection. The 3-year cumulative incidence of relapse (CIR), overall survival (OS), disease-free survival (DFS) and TRM were 13.7 ± 5.2, 67.8 ± 6.9, 68.1 ± 6.8 and 20.3% ± 6.1%, respectively. ROC curve showed that post-transplant MLL-PTD ≥ 1.0% was the optimal cut-off value for predicting hematological relapse after allo-HSCT. There was statistical difference between post-transplant MLL-PTD ≥ 1.0% and MLL-PTD < 1.0% groups (3-year CIR: 75% ± 15.3% vs. 0%, P < 0.001; 3-year OS: 25.0 ± 15.3% vs. 80.7% ± 6.6%, P < 0.001; 3-year DFS: 25.0 ± 15.3% vs. 80.7 ± 6.6%, P < 0.001; 3-year TRM: 0 vs. 19.3 ± 6.6%, P = 0.277). However, whether MLL-PTD ≥ 1% or MLL-PTD < 1% before transplantation has no significant difference on the prognosis., Conclusions: Our study indicated that MLL-PTD had a certain stability and could effectively reflect the change of tumor burden. The expression level of MLL-PTD after transplantation can serve as an effective indicator for predicting relapse., (© 2021. The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF