Department of Hematology, Catholic Hematology Hospital, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Leukemia Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Bone Marrow Transplant. 2021 Nov;56(11):2682-2689. doi: 10.1038/s41409-021-01384-w. Epub 2021 Jun 28.
Given the controversies in the prognostic value of KIT mutations and optimal thresholds and time points of MRD monitoring for AML with CBFB-MYH11, we retrospectively evaluated 88 patients who underwent allogeneic hematopoietic stem cell transplantation (Allo-HSCT, n = 60) or autologous HSCT (Auto-HSCT, n = 28). The D816V KIT mutation was significantly associated with post-transplant relapse, contrasting with other types of mutations in KIT. Pre- and post-transplant (3 months after transplant) CBFB-MYH11 MRD assessments were useful in predicting post-transplant relapse and poor survival. The optimal threshold was determined as a 2 log reduction at both time points. In multivariate analysis, the D816V KIT mutation and CBFB-MYH11 MRD assessments were independently associated with post-transplant relapse and survival. Stratification by D816V KIT and pre-transplant CBFB-MYH11 MRD status further distinguished the risk of relapse and survival. Auto-HSCT was superior to Allo-HSCT in MRD negative patients without D816V KIT, while Allo-HSCT trended to be superior to Auto-HSCT in patients with MRD positivity or the D816V KIT mutation. In conclusion, this study demonstrated the differentiated prognostic value of the D816V KIT mutation in AML with CBFB-MYH11 and clarified optimal time points and thresholds for CBFB-MYH11 MRD monitoring in the setting of HSCT.
鉴于 CBFB-MYH11 相关 AML 中 KIT 突变的预后价值以及 MRD 监测的最佳阈值和时间点存在争议,我们回顾性评估了 88 例接受异基因造血干细胞移植(Allo-HSCT,n=60)或自体 HSCT(Auto-HSCT,n=28)的患者。D816V KIT 突变与移植后复发显著相关,与 KIT 中的其他突变类型相反。移植前和移植后(移植后 3 个月)CBFB-MYH11 MRD 评估可用于预测移植后复发和不良生存。最佳阈值在两个时间点均确定为 2 个对数减少。多变量分析显示,D816V KIT 突变和 CBFB-MYH11 MRD 评估与移植后复发和生存独立相关。根据 D816V KIT 和移植前 CBFB-MYH11 MRD 状态进行分层,进一步区分了复发和生存的风险。在没有 D816V KIT 的 MRD 阴性患者中,Auto-HSCT 优于 Allo-HSCT,而在 MRD 阳性或 D816V KIT 突变患者中,Allo-HSCT 倾向于优于 Auto-HSCT。总之,本研究表明 D816V KIT 突变在 CBFB-MYH11 相关 AML 中具有不同的预后价值,并阐明了 HSCT 背景下 CBFB-MYH11 MRD 监测的最佳时间点和阈值。