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CAG (cytarabine, aclarubicin and granulocyte colony-stimulating factor) regimen for core binding factor acute myeloid leukaemia with measurable residual disease

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Abstract

Acute myeloid leukaemia (AML) with t (8;21) or inv (16), called core binding factor (CBF) AML, has a favourable prognosis. However, some CBF-AML patients have persistent measurable residual disease (MRD) and are more likely to relapse after standard chemotherapy treatment. The CAG regimen, composed of cytarabine, aclarubicin and granulocyte colony-stimulating factor, has been proven to be effective and safe in treating refractory AML patients. We performed a retrospective study to evaluate the efficacy of the CAG regimen to eliminate MRD detected by RUNX1::RUNX1T1 and CBFβ::MYH11 transcript levels by quantitative polymerase chain reaction (Q-PCR) among 23 patients. Molecular response was defined as the ratio of fusion transcript after treatment to that before treatment less than or equal to 0.5. The molecular response rate and median decrease ratio of fusion transcripts at the molecular level of the CAG regimen were 52% and 0.53, respectively. The median fusion transcripts before CAG treatment was 0.25% whereas after CAG was 0.11%. Among the 15 patients who had a poor molecular response to the high/intermediate-dose cytarabine regimen, the median decrease ratios of transcripts at the molecular level of high/intermediate-dose cytarabine and CAG were 1.55 and 0.53 (P = 0.028), respectively, and 6 of 15 patients achieved a molecular response to CAG (40%). The median disease-free survival was 18 months, and the overall survival rate at 3 years among all patients was 72.7% ± 10.7%. The common grades 3–4 adverse events were nausea (100%), thrombocytopenia (39%) and neutropenia (37.5%). The CAG regimen may have activity in CBF-AML patients and could provide a new option for patients who have a poor molecular response to high/intermediate-dose cytarabine.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

We thank the faculty and staff of the Clinical Unit of the Department of Haematology, the First Affiliated Hospital, Zhejiang University. We also appreciate Zhejiang Province Key Laboratory of Haematology Oncology Diagnosis and Treatment for their services in Q-PCR and quality control.

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Author notes

  1. Yao-jia Shen, Yi Zhang and Jie Chang have contributed equally to this work and share first authorship.

Authors and Affiliations

  1. Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China

    Yao-jia Shen, Jie Chang, Jie Jin & Hong-hu Zhu

  2. Department of Haematology, the First Affiliated Hospital, Zhejiang University School of Medicine, No.79 Qingchun Road, 310003, Hangzhou, Zhejiang Province, People’s Republic of China

    Yao-jia Shen, Yi Zhang, Jie Chang, Hua-feng Wang, Xing-nong Ye, Li Zhu, Jie Jin & Hong-hu Zhu

  3. Zhejiang Provincial Clinical Research Center for Haematological Disorders, Hangzhou, People’s Republic of China

    Yi Zhang, Hua-feng Wang, Xing-nong Ye, Li Zhu, Jie Jin & Hong-hu Zhu

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  1. Yao-jia Shen
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Contributions

ZH designed and supervised the clinical study. WH, ZL, YX and JJ enrolled patients and took care of the patients; SY and CJ collected and analysed the clinical data; SY performed statistical analysis. ZH, SY and ZY drafted and revised the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Hong-hu Zhu.

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This study was approved by the Institute Research Ethics Committee of the first Affiliated Hospital, College of Medicine, Zhejiang University.

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Written informed consent for publication was obtained.

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The authors declare no competing interests.

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Shen, Yj., Zhang, Y., Chang, J. et al. CAG (cytarabine, aclarubicin and granulocyte colony-stimulating factor) regimen for core binding factor acute myeloid leukaemia with measurable residual disease. Ann Hematol 102, 1731–1738 (2023). https://doi.org/10.1007/s00277-023-05213-6

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  • DOI: https://doi.org/10.1007/s00277-023-05213-6

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