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

Published on Jun 28, 2021in Bone Marrow Transplantation4.725
· DOI :10.1038/S41409-021-01384-W
Byung-Sik Cho19
Estimated H-index: 19
(Catholic University of Korea),
Gi-June Min2
Estimated H-index: 2
(Catholic University of Korea)
+ 16 AuthorsKi-Seong Eom18
Estimated H-index: 18
(Catholic University of Korea)
Sources
Abstract
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.
📖 Papers frequently viewed together
201317.54Blood
14 Authors (Hao Jiang, ..., Xiao-Jun Huang)
1 Citations
1 Citations
References33
Newest
#1Byung-Sik Cho (Catholic University of Korea)H-Index: 19
#2Gi-June Min (Catholic University of Korea)H-Index: 2
Last. Hee-Je Kim (Catholic University of Korea)H-Index: 25
view all 19 authors...
The prognostic significance of KIT mutations and optimal thresholds and time points of measurable residual disease (MRD) monitoring for acute myeloid leukemia (AML) with RUNX1-RUNX1T1 remain controversial in the setting of hematopoietic stem cell transplantation (HSCT). We retrospectively evaluated 166 high-risk patients who underwent allogeneic (Allo-HSCT, n = 112) or autologous HSCT (Auto-HSCT, n = 54). D816V KIT mutation, a subtype of exon 17 mutations, was significantly associated with post-...
1 CitationsSource
#1Wenbing Duan (PKU: Peking University)H-Index: 1
#2Xiaohong Liu (PKU: Peking University)H-Index: 1
Last. Hao Jiang (PKU: Peking University)H-Index: 68
view all 16 authors...
No consensus has been reached on the relationship between CBFB-MYH11 copies and prognosis. Of 1525 acute myeloid leukemia (AML) patients, 58 with CBFB-MYH11-positive AML (16/58 patients with c-kit mutation) were retrospectively analyzed with a median follow-up duration of 29.8 (range: 4.8-74.4) months. Of these, 25/58 (43.1%) patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), 10 of whom had the c-kit mutation. Of the 33 patients who did not undergo allo-HSCT, recu...
6 CitationsSource
#1Martin Sula (University of Bern)H-Index: 1
#2Ulrike Bacher (University of Bern)H-Index: 21
Last. Thomas Pabst (University of Bern)H-Index: 50
view all 6 authors...
4 CitationsSource
#1Yuichi Ishikawa (Nagoya University)H-Index: 16
#2Naomi Kawashima (Nagoya University)H-Index: 5
Last. Hitoshi Kiyoi (Nagoya University)H-Index: 65
view all 28 authors...
The prognostic impact of KIT mutation on core-binding factor acute myeloid leukemia (CBF-AML) remains controversial. We registered 199 newly diagnosed de novo CBF-AML patients, aged 16 to 64 years, who achieved complete remission. They received 3 courses of high-dose cytarabine therapy and no further treatment until hematological relapse. Mutations in exons 8, 10-11, and 17 of the KIT gene were analyzed. Furthermore, we analyzed mutations in 56 genes that are frequently identified in myeloid mal...
17 CitationsSource
#1Sabrina OpatzH-Index: 6
#2Stefanos A. Bamopoulos (LMU: Ludwig Maximilian University of Munich)H-Index: 6
Last. Philipp A. GreifH-Index: 25
view all 31 authors...
The fusion genes CBFB/MYH11 and RUNX1/RUNX1T1 block differentiation through disruption of the core binding factor (CBF) complex and are found in 10–15% of adult de novo acute myeloid leukemia (AML) cases. This AML subtype is associated with a favorable prognosis; however, nearly half of CBF-rearranged patients cannot be cured with chemotherapy. This divergent outcome might be due to additional mutations, whose spectrum and prognostic relevance remains hardly defined. Here, we identify nonsilent ...
24 CitationsSource
#1Jochen Greiner (University of Ulm)H-Index: 27
#2Marlies Götz (University of Ulm)H-Index: 12
Last. Verena Wais (University of Ulm)H-Index: 5
view all 5 authors...
Allogeneic stem cell transplantation (allo-SCT) is the preferred curative treatment for several hematological malignancies. The efficacy of allo-SCT depends on the graft-versus-leukemia (GvL) effect. However, the prognosis of patients with relapsed acute myeloid leukemia (AML) following allo-SCT is poor. Donor lymphocyte infusion (DLI) is utilized after allo-SCT in this setting to prevent relapse, to prolong progression free survival, to establish full donor chimerism and to restore the GvL effe...
9 CitationsSource
#1Guopan Yu (Southern Medical University)H-Index: 9
#2Changxin Yin (Southern Medical University)H-Index: 8
Last. Fan-Yi Meng (Southern Medical University)H-Index: 30
view all 10 authors...
Gene mutations play an important role in the development and progression of AML1-ETO-positive acute myeloid leukemia (AE-AML). Nevertheless, the gene mutation profile in this subtype of leukemia remains unclear. In addition, the clinical and prognostic effects of different mutant genes may be underestimated. In the present study, gene sequencing was conducted at diagnosis and relapse with next-generation sequencing (NGS) in 64 patients with newly diagnosed AE-AML, and 44/64 (68.8%) patients were...
5 CitationsSource
#1Panupong Hansrivijit (University of Texas MD Anderson Cancer Center)H-Index: 8
#2Robert Peter Gale (Imperial College London)H-Index: 137
Last. Stefan O. Ciurea (University of Texas MD Anderson Cancer Center)H-Index: 40
view all 4 authors...
Abstract Acute myeloid leukemia (AML) is a disease most commonly affecting older individuals with a high mortality. Despite the recent introduction of many novel agents, only a few were shown to significantly impact the outcome of this disease. Recent advances using chimeric antigen receptor (CAR) T-cells for B-cell acute lymphoblastic leukemia and non-Hodgkin's lymphoma have generated a tremendous interest for this strategy. Moreover, early results using high-dose natural killer (NK) cell thera...
26 CitationsSource
#1Katherine Tarlock (UW: University of Washington)H-Index: 10
#2Todd A. Alonzo (SC: University of Southern California)H-Index: 69
Last. Jessica A. Pollard (Harvard University)H-Index: 18
view all 18 authors...
Purpose:KIT mutations (KIT+) are common in core binding factor (CBF) AML and have been associated with varying prognostic significance. We sought to define the functional and clinical significance of distinct KIT mutations in CBF pediatric AML. Patients and Methods: Following transfection of exon 17 (E17) and exon 8 (E8) mutations into HEK293 and Ba/F3 cells, KIT phosphorylation, cytokine-independent growth, and response to tyrosine kinase inhibitors (TKI) were evaluated. Clinical outcomes of pa...
17 CitationsSource
#1Ho-Jin Shin (PNU: Pusan National University)H-Index: 17
#2Woo-Sung Min (Catholic University of Korea)H-Index: 23
Last. Hee-Je Kim (Catholic University of Korea)H-Index: 25
view all 14 authors...
Core-binding factor acute myeloid leukemia (CBF-AML) data in Asian countries has been rarely reported. We analyzed 392 patients with CBF-AML [281 with t(8;21), 111 with inv.(16)/t(16;16)] among data from 3041 patients with AML from the Korean AML Registry. Interestingly, del(9q) was less frequently detected in Korean than in German patients with t(8;21) (7.5% vs. 17%), and del(7q) was more frequently detected in Korean patients with inv(16). Overall survival (OS) was similar between patients in ...
6 CitationsSource
Cited By1
Newest
#1Xiao-Hui Zhang (PKU: Peking University)H-Index: 31
#2Jing ChenH-Index: 10
Last. Ting Liu (Sichuan University)H-Index: 18
view all 20 authors...
The consensus recommendations in 2018 from The Chinese Society of Hematology (CSH) on indications, conditioning regimens and donor selection for allogeneic hematopoietic stem cell transplantation (allo-HSCT) facilitated the standardization of clinical practices of allo-HSCT in China and progressive integration with the world. There have been new developments since the initial publication. To integrate recent developments and further improve the consensus, a panel of experts from the CSH recently...
Source