Validation of the prognostic value of the knowledge bank approach to determine AML prognosis in real life

Huet, Sarah; Lours, Camille; Grange, Béatrice; Courtois, Lucien; Chabane, Kaddour; Charlot, Carole; Mosnier, Isabelle; Simonet, Thomas; Hayette, Sandrine; Tigaud, Isabelle; Thomas, Xavier; Salles, Gilles; Subtil, Fabien; Sujobert, Pierre

doi:10.1182/blood-2018-03-840348

Cited by 19 publications

(25 citation statements)

References 6 publications

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“…As an example, in a simulation with the developed algorithm, allogeneic HSCT could savely be omitted in 25% of the patients resulting in the same OS rate. These results have also recently been confirmed by Huet et al [41] and indicate that a refined treatment approach accounting for a patient’s individual risk may be feasible in the future when broad application of NGS will be standardized for daily clinical practice.…”

Section: Prognostic Implication Of Gene Mutations In Amlsupporting

confidence: 69%

Next Generation Sequencing in AML—On the Way to Becoming a New Standard for Treatment Initiation and/or Modulation?

Leisch

Jansko

Zaborsky

et al. 2019

Cancers

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Acute myeloid leukemia (AML) is a clonal disease caused by genetic abberations occurring predominantly in the elderly. Next generation sequencing (NGS) analysis has led to a deeper genetic understanding of the pathogenesis and the role of recently discovered genetic precursor lesions (clonal hematopoiesis of indeterminate/oncogenic potential (CHIP/CHOP)) in the evolution of AML. These advances are reflected by the inclusion of certain mutations in the updated World Health Organization (WHO) 2016 classification and current treatment guidelines by the European Leukemia Net (ELN) and National Comprehensive Cancer Network (NCCN) and results of mutational testing are already influencing the choice and timing of (targeted) treatment. Genetic profiling and stratification of patients into molecularly defined subgroups are expected to gain ever more weight in daily clinical practice. Our aim is to provide a concise summary of current evidence regarding the relevance of NGS for the diagnosis, risk stratification, treatment planning and response assessment in AML, including minimal residual disease (MRD) guided approaches. We also summarize recently approved drugs targeting genetically defined patient populations with risk adapted- and individualized treatment strategies.

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Section: Prognostic Implication Of Gene Mutations In Amlsupporting

confidence: 69%

Next Generation Sequencing in AML—On the Way to Becoming a New Standard for Treatment Initiation and/or Modulation?

Leisch

Jansko

Zaborsky

et al. 2019

Cancers

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“…Testing of several machine learning models revealed that inclusive, multistage statistical models scored best in predicting OS and probabilities of non-remission death, relapse death, and death in CR1. Although a relatively small study [ 4 ] confirmed prognostic usefulness of KB approach, to our knowledge, it has not been hitherto validated in a large, independent patient cohort. Therefore, we applied the KB algorithm to 1612 adults with de novo AML and investigated whether additional cytogenetic and molecular alterations might improve its accuracy.…”

Section: To the Editormentioning

confidence: 99%

Precision oncology in AML: validation of the prognostic value of the knowledge bank approach and suggestions for improvement

et al. 2021

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Recently, a novel knowledge bank (KB) approach to predict outcomes of individual patients with acute myeloid leukemia (AML) was developed using unbiased machine learning. To validate its prognostic value, we analyzed 1612 adults with de novo AML treated on Cancer and Leukemia Group B front-line trials who had pretreatment clinical, cytogenetics, and mutation data on 81 leukemia/cancer-associated genes available. We used receiver operating characteristic (ROC) curves and the area under the curve (AUC) to evaluate the predictive values of the KB algorithm and other risk classifications. The KB algorithm predicted 3-year overall survival (OS) probability in the entire patient cohort (AUCKB = 0.799), and both younger (< 60 years) (AUCKB = 0.747) and older patients (AUCKB = 0.770). The KB algorithm predicted non-remission death (AUCKB = 0.860) well but was less accurate in predicting relapse death (AUCKB = 0.695) and death in first complete remission (AUCKB = 0.603). The KB algorithm’s 3-year OS predictive value was higher than that of the 2017 European LeukemiaNet (ELN) classification (AUC2017ELN = 0.707, p < 0.001) and 2010 ELN classification (AUC2010ELN = 0.721, p < 0.001) but did not differ significantly from that of the 17-gene stemness score (AUC17-gene = 0.732, p = 0.10). Analysis of additional cytogenetic and molecular markers not included in the KB algorithm revealed that taking into account atypical complex karyotype, infrequent recurrent balanced chromosome rearrangements and mutational status of the SAMHD1, AXL and NOTCH1 genes may improve the KB algorithm. We conclude that the KB algorithm has a high predictive value that is higher than those of the 2017 and 2010 ELN classifications. Inclusion of additional genetic features might refine the KB algorithm.

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“…Due to a better biomolecular definition and recent approval of various targeted therapies, the overall prognosis of acute myeloid leukemia (AML) is moving toward tremendous improvement. Recent advances in the discovery of the genomic landscape of the disease, in the development of assays for genetic testing and for detecting minimal residual disease (MRD), have recently modified AML management [ 1 , 2 , 3 ]. Rearrangement involving the Lysine (K)-specific Methyltransferase 2A ( KMT2A ) gene located at 11q23, formerly known as the mixed lineage leukemia ( MLL ) gene, is found in approximatively 3% of de novo AML [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Allogenic Stem Cell Transplantation Abrogates Negative Impact on Outcome of AML Patients with KMT2A Partial Tandem Duplication

Antherieu

Bidet

Huet

et al. 2021

Cancers

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Recently, a new subset of acute myeloid leukemia (AML) presenting a direct partial tandem duplication (PTD) of the KMT2A gene was described. The consequences of this alteration in terms of outcome and response to treatment remain unclear. We analyzed retrospectively a cohort of KMT2A-PTD-mutated patients with newly diagnosed AML. With a median follow-up of 3.6 years, the median overall survival was 12.1 months. KMT2A-PTD-mutated patients were highly enriched in mutations affecting epigenetic actors and the RTK/RAS signaling pathway. Integrating KMT2A-PTD in ELN classification abrogates its predictive value on survival suggesting that this mutation may overcome other genomic marker effects. In patients receiving intensive chemotherapy, hematopoietic stem cell transplantation (HSCT) significantly improved the outcome compared to non-transplanted patients. In the multivariate analysis, only HSCT at any time in complete remission (HR = 2.35; p = 0.034) and FLT3-ITD status (HR = 0.29; p = 0.014) were independent variables associated with overall survival, whereas age was not. In conclusion, our results emphasize that KMT2A-PTD should be considered as a potential adverse prognostic factor. However, as KMT2A-PTD-mutated patients are usually considered an intermediate risk group, upfront HSCT should be considered in first CR due to the high relapse rate observed in this subset of patients.

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Validation of the prognostic value of the knowledge bank approach to determine AML prognosis in real life

Cited by 19 publications

References 6 publications

Next Generation Sequencing in AML—On the Way to Becoming a New Standard for Treatment Initiation and/or Modulation?

Next Generation Sequencing in AML—On the Way to Becoming a New Standard for Treatment Initiation and/or Modulation?

Precision oncology in AML: validation of the prognostic value of the knowledge bank approach and suggestions for improvement

Allogenic Stem Cell Transplantation Abrogates Negative Impact on Outcome of AML Patients with KMT2A Partial Tandem Duplication

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