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

• Published in: BMC cancer 2022-01, Vol.22 (1), p.11-11, Article 11
• Main Authors: Kong, Jun, Gao, Meng-Ge, Qin, Ya-Zhen, Wang, Yu, Yan, Chen-Hua, Sun, Yu-Qian, Chang, Ying-Jun, Xu, Lan-Ping, Zhang, Xiao-Hui, Liu, Kai-Yan, Huang, Xiao-Jun, Zhao, Xiao-Su
• Format: Article
• Language: English
• Subjects: Acute myeloid leukemia; Allogeneic hematopoietic stem cell transplantation; Bone marrow; Care and treatment; Chemotherapy; Chromosome 11; Complications and side effects; Disease-Free Survival; Female; Follow-Up Studies; Gene Rearrangement - genetics; Hematology; Hematopoietic Stem Cell Transplantation; Hematopoietic stem cells; Histone-Lysine N-Methyltransferase - genetics; Humans; Karyotypes; Leukemia; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - mortality; Leukemia, Myeloid, Acute - surgery; Male; Medical prognosis; Middle Aged; Minimal residual disease; MLL protein; MLL-PTD; Myelocytic leukemia; Myelodysplastic syndrome; Myelodysplastic syndromes; Myelodysplastic Syndromes - genetics; Myelodysplastic Syndromes - mortality; Myelodysplastic Syndromes - surgery; Myeloid-Lymphoid Leukemia Protein - genetics; Neoplasm Recurrence, Local - genetics; Neoplasm Recurrence, Local - mortality; Neoplasm, Residual; Neutrophils; Nonlymphoid leukemia; Oncogene Proteins, Fusion - genetics; Patient outcomes; Patients; Polymerase chain reaction; Postoperative care; Postoperative Period; Predictive Value of Tests; Prognosis; Progression-Free Survival; Recurrence; Relapse; Remission (Medicine); Retrospective Studies; Stem cell transplantation; Transplantation; Transplantation, Homologous; Transplants & implants; Tumor Burden - genetics; Tumors
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-021-09051-5

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. 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. 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