Both the subtypes of KIT mutation and minimal residual disease are associated with prognosis in core binding factor acute myeloid leukemia: a retrospective clinical cohort study in single center

Duan, Wenbing; Liu, Xiaohong; Zhao, Xiaosu; Jia, Jinsong; Wang, Jing; Gong, Lizhong; Jiang, Qian; Zhao, Ting; Wang, Yu; Zhang, Mengjie; Xu, Lei; Shi, Hong-Xia; Chang, Ying‐Jun; Liu, Kai-Yan; Huang, Xiao‐Jun; Qin, Ya‐Zhen; Jiang, Hao

doi:10.1007/s00277-021-04432-z

Cited by 11 publications

(13 citation statements)

References 20 publications

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“…Among our study subjects, KIT mutation and FLT3 mutation were the two most common types of kinase‐activating gene mutations. Further analysis indicated a correlation between KIT mutations and lower OS rates, which has also been reported in multiple previous studies 11,12,22,23 …”

Section: Discussionsupporting

confidence: 82%

“…Further analysis indicated a correlation between KIT mutations and lower OS rates, which has also been reported in multiple previous studies. 11,12,22,23 According to the latest ELN risk stratification, similar to NPM1 mutations and CEBPA double mutations, inv(16) and t(8;21) are still classified into the favorable category. 15 However, in our CBF-AML group, the 3-year OS was only 63.6%, compared to 77.3% in the control group.…”

Section: Discussionmentioning

confidence: 99%

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Clinical characteristics and prognostic factors analysis of core binding factor acute myeloid leukemia in real world

Zhai,

Wang,

et al. 2023

Cancer Medicine

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BackgroundChromosomal translocations involving core binding factor (CBF) genes account for 15% of adult acute myeloid leukemia (AML) cases in China. Despite being classified as favorable‐risk by European Leukemia Net (ELN), CBF‐AML patients have a 40% relapse rate. This study aims to analyze clinical characteristics and prognosis of CBF‐AML, compare its subtypes (inv(16) and t(8;21)), and validate prognostic factors.MethodsRetrospective analysis of 149 AML patients (75 CBF‐AML, 74 non‐CBF) at Peking University First Hospital (March 2012–March 2022).ResultsCBF‐AML patients have significantly lower disease‐free survival (DFS) (p = 0.005) and higher non‐relapse mortality (NRM) (p = 0.028) compared to non‐CBF AML. inv (16) and t(8;21) show distinct co‐occurring gene mutation patterns, with inv(16) being prone to central nervous system (CNS) leukemia. Multivariate analysis identifies age as a risk factor for overall survival (OS) and disease free survival (DFS), kinase mutation as a risk factor for DFS and Recurrence, while WT1 mutation as a risk factor for OS and non relapse mortality (NRM) risk in t(8;21) AML. Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) improves prognosis in low‐risk t(8;21).ConclusionPrognosis of CBF‐AML is poorer than ELN guidelines suggest. inv(16) and (8;21) are separate entities with relatively poor prognoses, requiring rational risk stratification strategies. Allo‐HSCT may benefit low‐risk t(8;21), but further research is needed for conclusive evidence.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Clinical characteristics and prognostic factors analysis of core binding factor acute myeloid leukemia in real world

Zhai,

Wang,

et al. 2023

Cancer Medicine

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“…Accordingly, the French AML Intergroup [16] demonstrated that a more than 3-log MRD reduction after first consolidation, such as an absolute MRD2 level < or =0.1%, could be used to differentiate low-risk from high-risk patients. Moreover, the threshold of 0.1% resulted to impact on survival also at the end of the second consolidation cycle, as reported by the studies of Duan et al [31,32] Corbaciouglu et al [81] underlined the importance of MRD detection in the time window of consolidation and early months after the end of treatment: this timing turns out to be the most informative, in accordance with the median time of relapse occurrence. An early prediction of prognosis allows the clinicians to propose alternative strategies of consolidation.…”

Section: After Two Cycles Of Standard Induction/consolidation Chemotherapysupporting

confidence: 61%

“…Due to the debatable negative impact attributed to KIT mutation, CBF AML with KIT mutation was formerly assigned to the intermediate category, whereas more recent guidelines only stated that prognosis may be less favorable than CBF AML without such a mutation. When the two subtypes of CBF AML are considered, the majority of reports agree in conferring adverse prognosis in terms of relapse and sometimes [17,27] OS, mainly due to exon 17 mutation, in t(8:21) AML, as documented in some analyses restricted to D816 alteration, compared to other KIT mutations [14,26,32,41,46]. On the contrary, the impact of KIT mutations on inv( 16) is less well concerted (Table 2).…”

Section: Secondary Additional Genetic Abnormalitiesmentioning

confidence: 99%

“…Jourdan et al [16] recognized in MRD2 the timepoint to evaluate patients for transplant options. Qin et al [84] recommended allogeneic stem cell transplantation, if CBFB-MYH11 levels could not decrease to <0.2% after two courses of consolidation, improving RFS and OS [31,32] in these patients at high risk of relapse.…”

Section: After Two Cycles Of Standard Induction/consolidation Chemotherapymentioning

confidence: 99%

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How to Improve Prognostication in Acute Myeloid Leukemia with CBFB-MYH11 Fusion Transcript: Focus on the Role of Molecular Measurable Residual Disease (MRD) Monitoring

et al. 2021

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Acute myeloid leukemia (AML) carrying inv(16)/t(16;16), resulting in fusion transcript CBFB-MYH11, belongs to the favorable-risk category. However, even if most patients obtain morphological complete remission after induction, approximately 30% of cases eventually relapse. While well-established clinical features and concomitant cytogenetic/molecular lesions have been recognized to be relevant to predict prognosis at disease onset, the independent prognostic impact of measurable residual disease (MRD) monitoring by quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR), mainly in predicting relapse, actually supersedes other prognostic factors. Although the ELN Working Party recently indicated that patients affected with CBFB-MYH11 AML should have MRD assessment at informative clinical timepoints, at least after two cycles of intensive chemotherapy and after the end of treatment, several controversies could be raised, especially on the frequency of subsequent serial monitoring, the most significant MRD thresholds (most commonly 0.1%) and on the best source to be analyzed, namely, bone marrow or peripheral blood samples. Moreover, persisting low-level MRD positivity at the end of treatment is relatively common and not predictive of relapse, provided that transcript levels remain stably below specific thresholds. Rising MRD levels suggestive of molecular relapse/progression should thus be confirmed in subsequent samples. Further prospective studies would be required to optimize post-remission monitoring and to define effective MRD-based therapeutic strategies.

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Comparison of efficacy between homoharringtonine, aclarubicin, cytarabine (HAA) and idarubicin, cytarabine (IA) regimens as induction therapy in patients with de novo core binding factor acute myeloid leukemia

Duan,

Yang,

Zhao

et al. 2023

Ann Hematol

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Both the subtypes of KIT mutation and minimal residual disease are associated with prognosis in core binding factor acute myeloid leukemia: a retrospective clinical cohort study in single center

Cited by 11 publications

References 20 publications

Clinical characteristics and prognostic factors analysis of core binding factor acute myeloid leukemia in real world

Clinical characteristics and prognostic factors analysis of core binding factor acute myeloid leukemia in real world

How to Improve Prognostication in Acute Myeloid Leukemia with CBFB-MYH11 Fusion Transcript: Focus on the Role of Molecular Measurable Residual Disease (MRD) Monitoring

Comparison of efficacy between homoharringtonine, aclarubicin, cytarabine (HAA) and idarubicin, cytarabine (IA) regimens as induction therapy in patients with de novo core binding factor acute myeloid leukemia

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