Journal of Cancer Research and Clinical Oncology

, Volume 145, Issue 12, pp 3089–3097 | Cite as

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

  • Cai Xiu
  • Xiao LiEmail author
  • Lingyun WuEmail author
  • Feng Xu
  • Qi He
  • Zheng Zhang
  • Dong Wu
  • Luxi Song
  • Jiying Su
  • Liyu Zhou
  • Youshan Zhao
  • Ying Tao
  • Chunkang Chang
Original Article – Clinical Oncology



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.


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.


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.


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.


Myelodysplastic syndromes Decitabine Cytarabine Homoharringtonine Granulocyte colony-stimulating factor (G-CSF) 



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

Compliance with ethical standards

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.

Ethical approval

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.

Informed consent

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


  1. Bejar R, Steensma DP (2014) Recent developments in myelodysplastic syndromes. Blood 124:2793–2803CrossRefGoogle Scholar
  2. Bennett JM, Catovsky D, Daniel MT (1976) Proposals for the classification of the acute leukaemias: French-American-British Cooperative Group. Br J Haematol 33:451–458CrossRefGoogle Scholar
  3. Brunning R, Orazi A, Germing U et al (2008) Myelodysplastic syndromes. In: Swerdlow SH, Campo E, Harris NL et al (eds) WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th edn. IARC Press, Lyon, pp 87–104Google Scholar
  4. Cheson BD, Greenberg PL, Bennett JM et al (2006) Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood 108:419–425CrossRefGoogle Scholar
  5. Craddock C, Quek L, Goardon N et al (2013) Azacitidine fails to eradicate leukemic stem/progenitor cell populations in patients with acute myeloid leukemia and myelodysplasia. Leukemia 27:1028–1036CrossRefGoogle Scholar
  6. Feldman E, Arlin Z, Ahmed T et al (1992) Homoharringtonine in combination with cytarabine for patients with acute myelogenous leukemia. Leukemia 6:1189–1191PubMedGoogle Scholar
  7. Fenaux P, Mufti GJ, Hellstrom-Lindberg E et al (2009) Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 10:223–232CrossRefGoogle Scholar
  8. Germing U, Hildebrandt B, Pfeilstöcker M et al (2005) Refinement of the international prognostic scoring system (IPSS) by including LDH as an additional prognostic variable to improve risk assessment in patients with primary myelodysplastic syndromes (MDS). Leukemia 19:2223–2231CrossRefGoogle Scholar
  9. Greenberg P, Cox C, LeBeau MM et al (1997) International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 89:2079–2088CrossRefGoogle Scholar
  10. Greenberg PL, Tuechler H, Schanz J et al (2012) Revised international prognostic scoring system (IPSS-R) for myelodysplastic syndromes. Blood 120:2454–2465CrossRefGoogle Scholar
  11. Issa JP, Kantarjian HM (2009) Targeting DNA methylation. Clin Cancer Res 15:3938–3946CrossRefGoogle Scholar
  12. Jie H, Donghua H, Xingkui X et al (2007) Homoharringtonine-induced apoptosis of MDS cell line MUTZ-1 cells is mediated by the endoplasmic reticulum stress pathway. Leuk Lymphoma 48:964–977CrossRefGoogle Scholar
  13. Kantarjian H, Issa JP, Rosenfeld CS et al (2006) Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer 106:1794–1803CrossRefGoogle Scholar
  14. Li X, Chang C, He Q et al (2013) Cytogenetic response based on revised IPSS cytogenetic risk stratification and minimal residual disease monitoring by FISH in MDS patients treated with low-dose decitabine. Leuk Res 37:1516–1521CrossRefGoogle Scholar
  15. Saito K, Nakamura Y, Aoyagi M et al (2000) Low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor (CAG regimen) for previously treated patients with relapsed or primary resistant acute myelogenous leukemia (AML) and previously untreated elderly patients with AML, secondary AML, and refractory anemia with excess blasts in transformation. Int J Hematol 71:238–244PubMedGoogle Scholar
  16. Santini V (2012) Novel therapeutic strategies: hypomethylating agents and beyond. Hematology Am Soc Hematol Educ Program. 2012:65–73CrossRefGoogle Scholar
  17. Santini V (2019) How I treat MDS after hypomethylating agent failure. Blood 133:521–529CrossRefGoogle Scholar
  18. Tefferi A, Vardiman JW (2009) Myelodysplastic syndromes. N Engl J Med 361:1872–1885CrossRefGoogle Scholar
  19. Trotti A, Colevas AD, Setser A et al (2003) CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol 13:176–181CrossRefGoogle Scholar
  20. Wu L, Li X, Su J et al (2009) Effect of low-dose cytarabine, homoharringtonine and granulocyte colony-stimulating factor priming regimen on patients with advanced myelodysplastic syndrome or acute myeloid leukemia transformed from myelodysplastic syndrome. Leukemia Lymphoma 50:1461–1467CrossRefGoogle Scholar
  21. Wu L, Li X, Su J et al (2011) Efficacy and safety of CHG regimen (low-dose cytarabine, homoharringtonine with G-CSF priming) as induction chemotherapy for elderly patients with high-risk MDS or AML transformed from MDS. J Cancer Res Clin Oncol 137:1563–1569CrossRefGoogle Scholar
  22. Wu L, Li X, Chang C et al (2016) Efficacy and toxicity of decitabine versus CHG regimen (low-dose cytarabine, homoharringtonine and granulocyte colony-stimulating factor) in patients with higher risk myelodysplastic syndrome: a retrospective study. Leuk Lymphoma 57:1367–1374CrossRefGoogle Scholar
  23. Xie M, Jiang Q, Li L et al (2016) HAG (Homoharringtonine, Cytarabine, G-CSF) regimen for the treatment of acute myeloid leukemia and myelodysplastic syndrome: a meta-analysis with 2314 participants. PLoS One 11:e0164238CrossRefGoogle Scholar
  24. Xu F, Wu LY, Chang CK et al (2015) Whole-exome and targeted sequencing identify ROBO1 and ROBO2 mutations as progression-related drivers in myelodysplastic syndromes. Nat Commun 6:8806CrossRefGoogle Scholar
  25. Yamada K, Furusawa S, Saito K et al (1995) Concurrent use of granulocyte colony stimulating factor with low-dose cytosine arabinoside and aclarubicin for previously treated acute myelogenous leukemia: a pilot study. Leukemia 9:10–14PubMedGoogle Scholar
  26. Zhou JY, Chen DL, Shen ZS, Koeffler HP (1990) Effect of homoharringtonine on proliferation and differentiation of human leukemic cells in vitro. Cancer Res 50:2031–2035PubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of HematologyShanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghaiChina

Personalised recommendations