Allogeneic hematopoietic cell transplantation can overcome the adverse prognosis indicated by secondary-type mutations in de novo acute myeloid leukemia

Song, Ga‐Young; Kim, TaeHyung; Ahn, Seo-Yeon; Jung, Sung-Hoon; Kim, Mi-Hee; Yang, Deok‐Hwan; Lee, Je‐Jung; Choi, Seung Hyun; Kim, Mi Yeon; Jung, Chul Won; Jang, Jun‐Ho; Kim, Hee‐Je; Moon, Joon Ho; Sohn, Sang Kyun; Won, Jong-Ho; Park, Seong-Kyu; Kim, Sung-Hyun; Zhang, Zhaolei; Ahn, Jae‐Sook; Kim, HyeoungJoon; Kim, Dennis Dong Hwan

doi:10.1038/s41409-022-01817-0

Cited by 11 publications

(11 citation statements)

References 26 publications

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“…Previous studies that showed a potential adverse prognostic impact of myelodysplasia-related gene mutations all included less than 50% of patients receiving a consolidating allogeneic HSCT [12,24,25]. Furthermore, two independent studies indicated that patients with myelodysplasiarelated gene mutations might have improved outcomes with consolidating allogeneic HSCT, as compared to chemotherapy alone [12,26]. Similarly, in our transplanted patient population, myelodysplasia-related gene mutations did not associate with adverse outcomes when no other adverse risk characteristics were present.…”

Section: Discussionsupporting

confidence: 48%

Prognostic impact of the AML ELN2022 risk classification in patients undergoing allogeneic stem cell transplantation

et al. 2022

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For most patients with acute myeloid leukemia (AML), an allogeneic hematopoietic stem cell transplantation (HSCT) offers the highest chance of cure. Recently, the European LeukemiaNet (ELN) published updated recommendations on the diagnosis and risk classification in AML based on genetic factors at diagnosis as well as a dynamic adjustment (reclassification) according to the measurable residual disease (MRD) status for the favorable and intermediate risk groups. Validation of the ELN2022 risk classification has not been reported. We retrospectively analyzed 522 AML patients who received an HSCT at a median age of 59 (range 16–76) years. For patients with adequate material available and in remission prior to HSCT (n = 229), the MRD status was evaluated. Median follow-up after HSCT was 3.0 years. ELN2022 risk at diagnosis was in 22% favorable, in 26% intermediate, and in 52% adverse. ELN2022 risk at diagnosis is associated with the cumulative incidence of relapse/progression (CIR), event-free survival (EFS), and overall survival (OS) in the whole patient cohort, as well as the subgroup of patients transplanted in first remission. However, the risk stratification based on the ELN2022 classification did not significantly improve outcome prognostication in comparison to the ELN2017 classification. In our study, the newly added group of patients with myelodysplasia-related gene mutations did not have adverse outcomes. Re-classifying these patients into the intermediate risk group and adjusting the grouping for all AML patients by MRD at HSCT, led to a refined and improved risk stratification, which should be validated in independent studies.

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Section: Discussionsupporting

confidence: 48%

Prognostic impact of the AML ELN2022 risk classification in patients undergoing allogeneic stem cell transplantation

et al. 2022

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“…Several studies have demonstrated inferior outcomes in AML with MR gene mutations, but its independent prognostic value in de novo AML has been controversial [21][22][23]44 . Recent studies have shown that MR gene mutations in a favorable-risk group (mostly de novo) do not affect outcome 30,45 .…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, while WHO still retains ontogeny in the diagnostic hierarchy 18 , genomic features override ontogeny in ICC which means that ICC abandons t-AML and AML-MRC WHO2016 as diagnostic entities 19 . Concurrently, a few studies have shown inferior outcomes in AML patients carrying MR gene mutations 16,[20][21][22][23] . Therefore, these mutations have been universally added to the adverse-risk group by the ELN2022 2 .…”

Section: Introductionmentioning

confidence: 99%

Interaction between myelodysplasia-related gene mutations and ontogeny in acute myeloid leukemia: an appraisal of the new WHO and IC classifications and ELN risk stratification

McCarter

Nemirovsky

Famulare

et al. 2022

Preprint

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Accurate classification and risk stratification is critical for clinical decision making in AML patients. In the newly proposed World Health Organization (WHO) and International Consensus classifications (ICC) of hematolymphoid neoplasms, the presence of myelodysplasia-related (MR) gene mutations is included as one of the diagnostic criteria of AML, myelodysplasia-related (AML-MR), largely based on the assumption that these mutations are specific for AML with an antecedent myelodysplastic syndrome. ICC also prioritizes MR gene mutations over ontogeny (as defined by clinical history). Furthermore, European LeukemiaNet (ELN) 2022 stratifies these MR gene mutations to the adverse-risk group. By thoroughly annotating a cohort of 344 newly diagnosed AML patients treated at Memorial Sloan Kettering Cancer Center (MSKCC), we show that ontogeny assignment based on database registry lacks accuracy. MR gene mutations are frequently seen in de novo AML. Among MR gene mutations, only EZH2 and SF3B1 were associated with an inferior outcome in a univariate analysis. In a multivariate analysis, AML ontogeny had independent prognostic values even after adjusting for age, treatment, allo-transplant and genomic classes or ELN risks. Ontogeny also stratified the outcome of AML with MR gene mutations. Finally, de novo AML with MR gene mutations did not show an adverse outcome. In summary, our study emphasizes the importance of accurate ontogeny designation in clinical studies, demonstrates the independent prognostic value of AML ontogeny and questions the current classification and risk stratification of AML with MR gene mutations.

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“…The poor prognostic impact of myelodysplasia-related mutations in AML can be overcome by allogeneic stem cell transplantation. 100 The ICC also includes as an entity the AML with myelodysplasiarelated cytogenetic abnormalities, which is defined by a complex karyotype (≥3 unrelated clonal chromosomal abnormalities in the absence of other class-defining recurring genetic abnormalities), del(5q)/t(5q)/add(5q), À7/del(7q), + 8, del(12p)/t(12p)/add(12p), i(17q), À 17/add(17p) or del(17p), del(20q), or idic(X)(q13) clonal abnormalities (Figure 2) but lacking TP53 or myelodysplasia-related mutations. 101 This ICC entity retains the prior unbalanced cytogenetic abnormalities of AML-MRC, adding +8 and del(20q) because, in the presence of increased blasts, the latter abnormalities are regarded as myelodysplasia-related.…”

Section: Aml With Recurrent Genetic Abnormalitiesmentioning

confidence: 99%

“…Because cases with RUNX1 mutation almost always show mutations in the other genes characterizing AML with myelodysplasia‐related mutations, they are automatically included in this category and are not missed. The poor prognostic impact of myelodysplasia‐related mutations in AML can be overcome by allogeneic stem cell transplantation 100 …”

Section: Acute Myeloid Leukemiasmentioning

confidence: 99%

Comparison of the International Consensus and 5th WHO edition classifications of adult myelodysplastic syndromes and acute myeloid leukemia

Falini

Martelli

2023

American J Hematol

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Several editions of the World Health Organization (WHO) classifications of lympho‐hemopoietic neoplasms in 2001, 2008, and 2016 served as the international standard for diagnosis. Since the 4th WHO edition, here referred as WHO‐HAEM4, significant clinico‐pathological, immunophenotypic, and molecular advances have been made in the field of myeloid neoplasms, which have contributed to refine diagnostic criteria, to upgrade entities previously defined as provisional and to identify new entities. This process has resulted in two recent classification proposals of myeloid neoplasms: the International Consensus Classification (ICC) and the 5th edition of the WHO classification (WHO‐HAEM5). In this paper, we review and compare the two classifications in terms of diagnostic criteria and entity definition, with a focus on adult myelodysplastic syndromes/neoplasms (MDS) and acute myeloid leukemia (AML). The goal is to provide a tool to facilitate the work of pathologists, hematologists and researchers involved in the diagnosis and treatment of these hematological malignancies.

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Allogeneic hematopoietic cell transplantation can overcome the adverse prognosis indicated by secondary-type mutations in de novo acute myeloid leukemia

Cited by 11 publications

References 26 publications

Prognostic impact of the AML ELN2022 risk classification in patients undergoing allogeneic stem cell transplantation

Prognostic impact of the AML ELN2022 risk classification in patients undergoing allogeneic stem cell transplantation

Interaction between myelodysplasia-related gene mutations and ontogeny in acute myeloid leukemia: an appraisal of the new WHO and IC classifications and ELN risk stratification

Comparison of the International Consensus and 5th WHO edition classifications of adult myelodysplastic syndromes and acute myeloid leukemia

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