Classifying AML Patients with Inv(16) into High-Risk and Low-Risk Relapsed Patients Based on Peritransplantation Minimal Residual Disease Determined By CBFβ/MYH11 Gene Expression

• Published in: Blood 2018-11, Vol.132 (Supplement 1), p.4593-4593
• Main Authors: Zhao, Xiaosu, Cao, Leqing, Qin, Yazhen, Zhang, Xiaohui, Xu, Lanping, Huang, Xiaojun, Chang, Ying-Jun
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2018-99-114261

A subtype of patients with core binding factor acute myeloid leukemia (AML) is characterized by the presence of the presence of inv(16)(p13q22) and rarely by a translocation t(16;16)(p13;q22). The final genetic product is the fusion of the CBFβ gene at 16q22 to the smooth muscle myosin heavy chain (MYH11) at 16p13, which is termed as CBFβ/MYH11 fusion gene. Although this type of AML is considered a favorable cytogenetic subgroup both in NCCN guideline or ELN classification, in particular with the application of high-dose cytarabine-based consolidation chemotherapy regimens, disease relapse remains one of the most important causes leading to death, occurring in around 35% of patients. Thus, for this cohort of patients, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is needed to as salvage treatment to improve the overall survival. It has been reported that when patients achieved hematological remission, the MRD prior to transplantation (pre-MRD) has been demonstrated to be a useful parameter to predict leukemia relapse after allo-HSCT. Evaluating minimal residual disease (MRD) by real-time quantitative reverse transcriptase polymerase chain reaction (RQ-PCR) can quantify the expression level of fusion transcript at different time points along with the treatment. More recently, CBFβ/MYH11 fusion gene has been confirmed to be a good MRD marker and further screening out the patients in high-risk of relapse either during the treatment or after transplantation. However, due to the limit number of patients, there has been no studies about predictive value of CBFβ/MYH11expression after allo-HSCT. Therefore, in this study, we attempted to investigate the impact of pre-MRD determined by RQ-PCR-based CBFβ/MYH11 gene expression on transplant outcomes of AML patients with inv(16)(p13q22) or t(16;16)(p13;q22). Besides, our previous studies has demonstrated that in compared to HLA-identical transplantation, haplo-identical allo-HSCT had superior graft-versus-leukemia (GVL) effect in AML patients with standard-risk. Thus, here we also wanted to know whether the level of CBFβ/MYH11 pretransplant could further divide this form of AML into high-risk and low-risk relapse patients before allo-HSCT. Ninety AML patients with inv(16) in complete remission (CR) were monitored CBFβ/MYH11 transcript before and after allo-HSCT as MRD. A total of 23 patients received HLA-matched sibling donor transplantation (MSDT) and 67 patients received unmanipulated haploidentical