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Acute myeloid leukemia

Response kinetics and factors predicting survival in core-binding factor leukemia

Leukemia volume 32, pages 2698–2701 (2018)Cite this article

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Core-binding factor (CBF) acute myeloid leukemia (AML) is characterized by t(8;21)(q22;q22) and inv(16)(p13;q22)/t(16;16)(p13;q22) abnormalities, and despite mutational and cytogenetic heterogeneity among t(8;21) and inv(16), these entities share similarities in prognosis, are grouped together, and managed similarly [1]. Our historical data demonstrated that fludarabine-based (fludarabine, cytarabine, and G-CSF) frontline regimens may be superior to the traditional anthracycline and cytarabine combination regimen in treating CBF leukemia [2]. FLAG when combined either with gemtuzumab ozogamicin (FLAG-GO) [2] or idarubicin (FLAG-IDA) [3] has resulted in high remission rates and impressive long-term disease-free and overall survival when employed in the frontline setting.

The detection of RUNX1/RUNX1T1 (in t(8;21)) and CBFB/MYH11 (in inv(16)) gene-fusion transcripts by quantitative real-time PCR (qPCR) affords a highly sensitive and precise technique for disease monitoring and response to treatment [4]. Relevant cutoff levels predicting relapse vary based on cytogenetic subgroup, timing of the analyzed sample, and source (peripheral blood or bone marrow) [5,6,7,8,9,10,11,12,13]. Promising results using the FLAG-based treatment prompted us to assess the prognostic utility of depth and slope (rapidity) of reduction of qPCR levels on relapse and survival in this treatment setting.

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References

  1. Appelbaum FR, Kopecky KJ, Tallman MS, Slovak ML, Gundacker HM, Kim HT, et al. The clinical spectrum of adult acute myeloid leukaemia associated with core binding factor translocations. Br J Haematol. 2006;135:165–73.

    Article  Google Scholar 

  2. Borthakur G, Kantarjian H, Wang X, Plunkett WK Jr., Gandhi VV, Faderl S, et al. Treatment of core-binding-factor in acute myelogenous leukemia with fludarabine, cytarabine, and granulocyte colony-stimulating factor results in improved event-free survival. Cancer. 2008;113:3181–5.

    Article  Google Scholar 

  3. Borthakur G, Cortes JE, Estey EE, Jabbour E, Faderl S, O’Brien S, et al. Gemtuzumab ozogamicin with fludarabine, cytarabine, and granulocyte colony stimulating factor (FLAG-GO) as front-line regimen in patients with core binding factor acute myelogenous leukemia. Am J Hematol. 2014;89:964–8.

    Article  CAS  Google Scholar 

  4. Solh M, Yohe S, Weisdorf D, Ustun C. Core-binding factor acute myeloid leukemia: heterogeneity, monitoring, and therapy. Am J Hematol. 2014;89:1121–31.

    Article  Google Scholar 

  5. Schnittger S, Weisser M, Schoch C, Hiddemann W, Haferlach T, Kern W. New score predicting for prognosis in PML-RARA+, AML1-ETO+, or CBFBMYH11+ acute myeloid leukemia based on quantification of fusion transcripts. Blood. 2003;102:2746–55.

    Article  CAS  Google Scholar 

  6. Leroy H, de Botton S, Grardel-Duflos N, Darre S, Leleu X, Roumier C, et al. Prognostic value of real-time quantitative PCR (RQ-PCR) in AML with t(8;21). Leukemia. 2005;19:367–72.

    Article  CAS  Google Scholar 

  7. Stentoft J, Hokland P, Ostergaard M, Hasle H, Nyvold CG. Minimal residual core binding factor AMLs by real time quantitative PCR—initial response to chemotherapy predicts event free survival and close monitoring of peripheral blood unravels the kinetics of relapse. Leuk Res. 2006;30:389–95.

    Article  CAS  Google Scholar 

  8. Weisser M, Haferlach C, Hiddemann W, Schnittger S. The quality of molecular response to chemotherapy is predictive for the outcome of AML1-ETO-positive AML and is independent of pretreatment risk factors. Leukemia. 2007;21:1177–82.

    Article  CAS  Google Scholar 

  9. Lane S, Saal R, Mollee P, Jones M, Grigg A, Taylor K, et al. A or =1 log rise in RQ-PCR transcript levels defines molecular relapse in core binding factor acute myeloid leukemia and predicts subsequent morphologic relapse. Leuk Lymphoma. 2008;49:517–23.

    Article  CAS  Google Scholar 

  10. Narimatsu H, Iino M, Ichihashi T, Yokozawa T, Hayakawa M, Kiyoi H, et al. Clinical significance of minimal residual disease in patients with t(8;21) acute myeloid leukemia in Japan. Int J Hematol. 2008;88:154–8.

    Article  Google Scholar 

  11. Yin JA, O’Brien MA, Hills RK, Daly SB, Wheatley K, Burnett AK. Minimal residual disease monitoring by quantitative RT-PCR in core binding factor AML allows risk stratification and predicts relapse: results of the United Kingdom MRC AML-15 trial. Blood. 2012;120:2826–35.

    Article  CAS  Google Scholar 

  12. Zhu HH, Zhang XH, Qin YZ, Liu DH, Jiang H, Chen H, et al. MRD-directed risk stratification treatment may improve outcomes of t(8;21) AML in the first complete remission: results from the AML05 multicenter trial. Blood. 2013;121:4056–62.

    Article  CAS  Google Scholar 

  13. Krauter J, Gorlich K, Ottmann O, Lubbert M, Dohner H, Heit W, et al. Prognostic value of minimal residual disease quantification by real-time reverse transcriptase polymerase chain reaction in patients with core binding factor leukemias. J Clin Oncol. 2003;21:4413–22.

    Article  CAS  Google Scholar 

  14. Ragon BK, Daver N, Garcia-Manero G, Ravandi F, Cortes J, Kadia T, et al. Minimal residual disease eradication with epigenetic therapy in core binding factor acute myeloid leukemia. Am J Hematol. 2017;92:845–50.

    Article  CAS  Google Scholar 

  15. Marcucci G, Mrozek K, Ruppert AS, Maharry K, Kolitz JE, Moore JO, et al. Prognostic factors and outcome of core binding factor acute myeloid leukemia patients with t(8;21) differ from those of patients with inv(16): a cancer and leukemia group B study. J Clin Oncol. 2005;23:5705–17.

    Article  Google Scholar 

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Funding

This paper was supported in part by the MD Anderson Cancer Center Leukemia Support Grant CA016672 and generous philanthropic contributions to the MD Anderson Moon Shots Program.

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Authors and Affiliations

  1. Department of Leukemia, MD Anderson Cancer center, Houston, TX, USA

    Prajwal Boddu, Jorge Cortes, Mary Akosile, Farhad Ravandi, Guillermo Garcia-Manero, Tapan Kadia, Mark Brandt, Rita Maduike, Hagop Kantarjian & Gautam Borthakur

  2. UT school of medicine, UT Health sciences, Houston, TX, USA

    Christopher Gurguis

  3. Department of Hematology, University of British Columbia, Vancouver, BC, Canada

    David Sanford

  4. Department of Hematopathology, MD Anderson Cancer center, Houston, TX, USA

    Keyur P Patel

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  1. Prajwal Boddu
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Correspondence to Gautam Borthakur.

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Boddu, P., Gurguis, C., Sanford, D. et al. Response kinetics and factors predicting survival in core-binding factor leukemia. Leukemia 32, 2698–2701 (2018). https://doi.org/10.1038/s41375-018-0158-1

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