Prognostic values of D816V KIT mutation and peri-transplant CBFB-MYH11 MRD monitoring on acute myeloid leukemia with CBFB-MYH11

• Published in: Bone marrow transplantation (Basingstoke) Vol. 56; no. 11; pp. 2682 - 2689
• Main Authors: Cho, Byung-Sik, Min, Gi-June, Park, Sung-Soo, Park, Silvia, Jeon, Young-Woo, Shin, Seung-Hwan, Yahng, Seung-Ah, Yoon, Jae-Ho, Lee, Sung-Eun, Eom, Ki-Seong, Kim, Yoo-Jin, Lee, Seok, Min, Chang-Ki, Cho, Seok-Goo, Kim, Dong-Wook, Lee, Jong Wook, Kim, Myungshin, Kim, Yonggoo, Kim, Hee-Je
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.11.2021; Nature Publishing Group
• Subjects: 45/23; 45/77; 631/208/69; 631/67/1990/283/1897; 692/308/575; 692/699/1541/1990/283/1897; Acute myeloid leukemia; Assessments; Autografts; Cell Biology; Core Binding Factor beta Subunit - genetics; Gene mutations; Health aspects; Hematology; Hematopoietic Stem Cell Transplantation; Hematopoietic stem cells; Humans; Internal Medicine; Leukemia; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - therapy; Medicine; Medicine & Public Health; Monitoring; Multivariate analysis; Mutation; Myeloid leukemia; Myosin Heavy Chains - genetics; Neoplasm, Residual - diagnosis; Neoplasm, Residual - genetics; Prognosis; Public Health; Retrospective Studies; Stem cell transplantation; Stem Cells; Survival; Thresholds; Transplantation; Transplants & implants; South Korea
• ISSN: 0268-3369; 1476-5365; 1476-5365
• DOI: 10.1038/s41409-021-01384-w

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.