How to improve prognostication in acute myeloid leukemia with cbfb‐myh11 fusion transcript: Focus on the role of molecular measurable residual disease (mrd) monitoring

Annalisa Talami, Francesca Bettelli, Valeria Pioli, Davide Giusti, Andrea Gilioli, Corrado Colasante, Laura Galassi, Rachele Giubbolini, Hillary Catellani, Francesca Donatelli, Rossana Maffei, Silvia Martinelli, Patrizia Barozzi, Leonardo Potenza, Roberto Marasca, Tommaso Trenti, Enrico Tagliafico, Patrizia Comoli, Mario Luppi, Fabio Forghieri

Research output: Contribution to journalArticlepeer-review

Abstract

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 postremission monitoring and to define effective MRD‐based therapeutic strategies.

Original languageEnglish
Article number953
JournalBiomedicines
Volume9
Issue number8
DOIs
Publication statusPublished - Aug 2021

Keywords

  • Acute myeloid leukemia
  • CBFB‐MYH11 fusion transcript
  • Clinical outcomes
  • Intensive chemotherapy
  • Molecular measurable residual disease monitoring
  • Prognostic thresholds and timepoints

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)

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