Minimal residual disease eradication with epigenetic therapy in core binding factor acute myeloid leukemia

Brittany Knick Ragon, Naval Daver, Guillermo Garcia-Manero, Farhad Ravandi, Jorge Cortes, Tapan Kadia, Betul Oran, Maro Ohanian, Alessandra Ferrajoli, Naveen Pemmaraju, Hagop M. Kantarjian, Gautam Borthakur

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Recurrent translocations, t(8;21) or inv(16), in core binding factor acute myeloid leukemia (CBF-AML) are amenable to monitoring for minimal residual disease (MRD) with reverse transcriptase polymerase chain reaction (RTPCR). Despite a favorable prognosis, disease relapse remains the single cause of treatment failure in CBF-AML. Fusion products of these translocations recruit epigenetic silencing complexes resulting in hematopoietic maturation arrest. We hypothesized that maintenance therapy with hypomethylating agents (HMA), including decitabine (DAC) and azacitidine (AZA) after induction/consolidation, can be used for MRD elimination to ultimately prolong relapse free survival. Real-time quantitative (RTPCR) trends were reviewed in 23 patients (median age 53 years) with CBF-AML that received HMA therapy following induction/consolidation with fludarabine, cytarabine, and G-CSF (FLAG) with low dose gemtuzumab or idarubicin (NCT00801489). Of the 23 patients evaluated, 17 had a detectable RTPCR at HMA initiation. Five patients had progressive disease and a notable increase in RTPCR values over 1-2 cycles of HMA therapy. Twelve patients did not fail HMA and had a median RTPCR at HMA initiation of 0.06 (range, 0.01-0.91). Unlike the HMA failure subset, 11 of these patients had a reduction in RTPCR after the first or second cycle of HMA. Our data suggests that CBF-AML patients with low levels of RTPCR (between 0.01 and 0.05) at the conclusion of induction/consolidation chemotherapy benefit most from maintenance HMA, particularly those that have a reduction in the RTPCR within the first two cycles of HMA therapy.

Original languageEnglish (US)
Pages (from-to)845-850
Number of pages6
JournalAmerican Journal of Hematology
Volume92
Issue number9
DOIs
StatePublished - Sep 2017
Externally publishedYes

ASJC Scopus subject areas

  • Hematology

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    Ragon, B. K., Daver, N., Garcia-Manero, G., Ravandi, F., Cortes, J., Kadia, T., Oran, B., Ohanian, M., Ferrajoli, A., Pemmaraju, N., Kantarjian, H. M., & Borthakur, G. (2017). Minimal residual disease eradication with epigenetic therapy in core binding factor acute myeloid leukemia. American Journal of Hematology, 92(9), 845-850. https://doi.org/10.1002/ajh.24782