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The efficacy and toxicity of the CHG priming regimen (low-dose cytarabine, homoharringtonine, and G-CSF) in higher risk MDS patients relapsed or refractory to decitabine

  • Original Article – Clinical Oncology
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Abstract

Purpose

Myelodysplastic syndromes (MDSs) refractory or relapsed after hypomethylating agents (HMAs) remain a therapeutic challenge. The CHG regimen has been demonstrated to be effective in initially treating higher risk MDS. The current study evaluated the efficacy and toxicity of the CHG regimen in patients who were resistant to decitabine.

Methods

Patients with higher risk MDS relapsed or refractory to decitabine were enrolled in this study. Each patient received the CHG regimen (cytarabine (25 mg/day, days 1–14) and homoharringtonine (1 mg/day, days 1–14) intravenously with G-CSF (300 μg/day) subcutaneously from day 0 until neutrophil count recovery to 2.0 × 109 cells/L). Next gene sequencing with a 31-gene panel was carried out in patients.

Results

Thirty-three patients were enrolled, including 12 relapsed and 21 refractory cases. The overall response rate (ORR) was 39.4% (13 of 33), with 9 (27.3%) achieving complete remission (CR), 2 having marrow CR (mCR), and 2 achieving partial remission (PR). The CR rate was higher in patients harboring fewer gene mutations (0–1) (55.6%) than in those with more gene mutations (> 1) (12.5%) (p = 0.021). The median overall survival (OS) of the 33 patients was 7.0 months. Patients who achieved a response had significantly longer survival times than were found in those without a response (21.0 M vs. 4.0 M, p < 0.0001). The regimen was endurable for most of the patients.

Conclusions

The CHG priming regimen provided a safe and effective salvage regimen for higher risk MDS patients who were resistant to decitabine. Further studies involving larger samples will be needed. Clinical trial No. ChiCTR-ONC-11001501.

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Funding

This work was supported by the National Science Foundation of China (81670121).

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Author notes

  1. Cai Xiu and Xiao Li are co-first authors.

Authors and Affiliations

  1. Department of Hematology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, 200233, China

    Cai Xiu, Xiao Li, Lingyun Wu, Feng Xu, Qi He, Zheng Zhang, Dong Wu, Luxi Song, Jiying Su, Liyu Zhou, Youshan Zhao, Ying Tao & Chunkang Chang

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  1. Cai Xiu
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  2. Xiao Li
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Corresponding authors

Correspondence to Xiao Li or Lingyun Wu.

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Conflict of interest

Lingyun Wu has received research grants from National Science Foundation of China and declares that she has no conflict of interest. Cai Xiu, Xiao Li, Feng Xu, Qi He, Zheng Zhang, Dong Wu, Luxi Song, Jiying Su, Liyu Zhou, Youshan Zhao, Ying Tao, and Chunkang Chang declare that they have no conflict of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed written consent was obtained from all individual participants included in the study.

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Xiu, C., Li, X., Wu, L. et al. The efficacy and toxicity of the CHG priming regimen (low-dose cytarabine, homoharringtonine, and G-CSF) in higher risk MDS patients relapsed or refractory to decitabine. J Cancer Res Clin Oncol 145, 3089–3097 (2019). https://doi.org/10.1007/s00432-019-03031-w

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  • DOI: https://doi.org/10.1007/s00432-019-03031-w

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