Prospective evaluation of prognostic impact of KIT mutations on acute myeloid leukemia with RUNX1-RUNX1T1 and CBFB-MYH11

Ishikawa, Yuichi; Kawashima, Naomi; Atsuta, Yoshiko; Sugiura, Isamu; Sawa, Masashi; Dobashi, Nobuaki; Yokoyama, Hisayuki; Doki, Noriko; Tomita, Akihiro; Kiguchi, Toru; Koh, Shiro; Kanamori, Heiwa; Iriyama, Noriyoshi; Kohno, Akio; Moriuchi, Yukiyoshi; Asada, Noboru; Hirano, Daiki; Togitani, Kazuto; Sakura, Toru; Hagihara, Maki; Tomikawa, Tatsuki; Yokoyama, Yasuhisa; Asou, Norio; Ohtake, Shigeki; Matsumura, Itaru; Miyazaki, Yasushi; Naoe, Tomoki; Kiyoi, Hitoshi

doi:10.1182/bloodadvances.2019000709

Cited by 64 publications

(63 citation statements)

References 33 publications

(43 reference statements)

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“…Thus, they are not included in guidelines for risk stratification in the current ELN guideline [ 13 ]. However, recent studies have reported the prognostic importance of KIT mutations in AML with RUNX1–RUNX1T1, but not in those with CBFB-MYH11 [ 8 , 23 ]. Prognostic impacts of each type of KIT mutations may be different [ 8 , 9 , 14 ].…”

Section: Discussionmentioning

confidence: 99%

“…However, recent studies have reported the prognostic importance of KIT mutations in AML with RUNX1–RUNX1T1, but not in those with CBFB-MYH11 [ 8 , 23 ]. Prognostic impacts of each type of KIT mutations may be different [ 8 , 9 , 14 ]. Compared to other KIT mutations, exons 17 and/or 8 mutations are more likely to adversely affect survival [ 8 , 9 , 14 ].…”

Section: Discussionmentioning

confidence: 99%

“…However, it is also a heterogeneous disease entailing different prognoses [ 1 , 2 , 3 ]. Several prognostic factors, including KIT mutations and measurable residual disease (MRD) status, have been proposed [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 ]. Many types of KIT mutations have been identified in AML, and their prognostic significance has been conflicting so far [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

“…Thus, the current European Leukemia Net (ELN) guideline does not support the use of KIT mutational status in clinical guidance in terms of therapeutic intervention [ 13 ]. However, recent studies have suggested different prognostic significance of each type of KIT mutations [ 8 , 9 , 14 ]. A recent prospective study has demonstrated that KIT mutations in exon 17 among three mutation hot-spots (exon 8, exon 10–11, and exon 17) are only prognostic for AML with RUNX1-RUNX1T1 through evaluation of all types of KIT mutations [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

“…However, recent studies have suggested different prognostic significance of each type of KIT mutations [ 8 , 9 , 14 ]. A recent prospective study has demonstrated that KIT mutations in exon 17 among three mutation hot-spots (exon 8, exon 10–11, and exon 17) are only prognostic for AML with RUNX1-RUNX1T1 through evaluation of all types of KIT mutations [ 8 ]. RUNX1-RUNX1T1 quantification by real-time quantitative polymerase chain reaction (RT-qPCR) is useful as an MRD tool for predicting relapse [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

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Prognostic Impacts of D816V KIT Mutation and Peri-Transplant RUNX1–RUNX1T1 MRD Monitoring on Acute Myeloid Leukemia with RUNX1–RUNX1T1

Cho

Min

Park

et al. 2021

Cancers

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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-transplant relapse and poor survival, while other types of mutations in exons 17 and 8 were not associated with post-transplant relapse. Pre- and post-transplant RUNX1–RUNX1T1 MRD assessments were useful for predicting post-transplant relapse and poor survival with a higher sensitivity at later time points. Survival analysis for each stratified group by D816V KIT mutation and pre-transplant RUNX1–RUNX1T1 MRD status demonstrated that Auto-HSCT was superior to Allo-HSCT in MRD-negative patients without D816V KIT mutation, while Allo-HSCT was superior to Auto-HSCT in MRD-negative patients with D816V KIT mutation. Very poor outcomes of pre-transplant MRD-positive patients with D816V KIT mutation suggested that this group should be treated in clinical trials. Risk stratification by both D816V KIT mutation and RUNX1–RUNX1T1 MRD status will provide a platform for decision-making or risk-adapted therapeutic approaches.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Prognostic Impacts of D816V KIT Mutation and Peri-Transplant RUNX1–RUNX1T1 MRD Monitoring on Acute Myeloid Leukemia with RUNX1–RUNX1T1

Cho

Min

Park

et al. 2021

Cancers

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Acute Myeloid Leukemia in Adults: Mast Cell Leukemia and Other Mast Cell Neoplasms

Stone¹,

Schiffer²,

DeAngelo³

2022

Holland‐Frei Cancer Medicine

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Overview Acute myeloid leukemia (AML) is a heterogeneous disease characterized by unbridled proliferation of myeloid stem cells resulting in bone marrow failure and death without effective therapy. The median age of AML is approximately 70; predisposing factors include inherited mutations, exposure to industrial solvents, ionizing radiation, or certain chemotherapy given for other malignancies or conditions. The disease results from the accumulation of mutations in pathways that promote cellular proliferation or impairing differentiation. Prognosis is based on a combination of host and disease factors, especially diagnostic cytogenetics and genomics. In younger fit patients, therapy consists of myelosuppressive induction chemotherapy to minimize disease burden and allow restoration of normal hematopoiesis. Postremission chemotherapy with additional myelo‐intense chemotherapy and/or allogeneic stem cell transplant is required to potentiate cure. In older and less fit patients (perhaps those with adverse prognosis) the current standard is repetitive cycles of a hypomethylating agent or low‐dose cytarabine plus the BCL‐2 inhibitor, venetoclax. The application of molecularly targeted therapies at both diagnosis and relapse may change the natural history of the disease, the management of which requires a comprehensive integration of disparate fields including social work, nutrition, pharmacy, blood bank, and medical oncology.

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Lower relapse incidence with haploidentical versus matched sibling or unrelated donor hematopoietic cell transplantation for core‐binding factor AML patients in CR2: A study from the Global Committee and the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

Ye,

Labopin,

Gérard

et al. 2024

American J Hematol

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Allogeneic hematopoietic cell transplantation (allo‐HCT) is recommended for core‐binding factor mutated (CBF) AML patients achieving second complete remission (CR2). However, approximately 20% of patients may relapse after transplant and donor preference remains unclear. We compared in this EBMT global multicenter registry‐based analysis the allo‐HCT outcomes using either haploidentical (Haplo), matched siblings donors (MSD), or 10/10 matched unrelated donors (MUD). Data from 865 de novo adult CBF AML patients in CR2 receiving allo‐HCT in 227 EBMT centers from 2010 to 2022 were analyzed, in which 329 MSD, 374 MUD, and 162 Haplo‐HCTs were included. For the entire cohort, 503 (58%) patients were inv(16)/CBFB‐MYH11 and 362 patients (42%) were t(8;21)/RUNX1‐RUNX1T1 AML. On multivariate analysis, Haplo‐HCT was associated with a lower Relapse Incidence (RI) compared to either MSD (hazard ratio [HR] = 0.56, 95% CI 0.32–0.97; p < .05) or MUD (HR = 0.57, 95% CI: 0.33–0.99, p < .05). No significant difference was observed among the 3 types of donors on LFS, OS and GRFS. CBF‐AML with t(8;21) was associated with both higher RI (HR = 1.79, 95% CI 1.3–2.47; p < .01) and higher NRM (HR = 1.58, 95% CI 1.1–2.27; p < .01) than CBF‐AML with inv(16), which led to worse LFS, OS and GRFS. To conclude, for CBF‐AML patients in CR2, Haplo‐HCTs were associated with a lower RI compared to MSD and MUD allo‐HCTs. There was no difference on LFS, OS or GRFS. CBF AML patients with inv(16) had a better progonosis than those with t(8;21) after allo‐HCT in CR2.

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Prospective evaluation of prognostic impact of KIT mutations on acute myeloid leukemia with RUNX1-RUNX1T1 and CBFB-MYH11

Abstract: Key Points KIT exon 17 mutation is a poor prognostic factor in AML patients with RUNX1-RUNX1T1, but not in those with CBFB-MYH11. NRAS mutation is a poor prognostic factor in AML patients with CBFB-MYH11.

Cited by 64 publications

References 33 publications

Prognostic Impacts of D816V KIT Mutation and Peri-Transplant RUNX1–RUNX1T1 MRD Monitoring on Acute Myeloid Leukemia with RUNX1–RUNX1T1

Prognostic Impacts of D816V KIT Mutation and Peri-Transplant RUNX1–RUNX1T1 MRD Monitoring on Acute Myeloid Leukemia with RUNX1–RUNX1T1

Acute Myeloid Leukemia in Adults: Mast Cell Leukemia and Other Mast Cell Neoplasms

Lower relapse incidence with haploidentical versus matched sibling or unrelated donor hematopoietic cell transplantation for core‐binding factor AML patients in CR2: A study from the Global Committee and the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

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