Decitabine priming prior to low-dose chemotherapy improves patient outcomes in myelodysplastic syndromes-RAEB: a retrospective analysis vs. chemotherapy alone

Li Ye; Yanling Ren; Xinping Zhou; Chen Mei; Liya Ma; Xingnong Ye; Juying Wei; Weilai Xu; Haitao Meng; Wenbin Qian; Wenyuan Mai; Yinjun Lou; Gaixiang Xu; Jiejing Qian; Yejiang Lou; Yingwan Luo; Lili Xie; Peipei Lin; Chao Hu; Jie Jin; Hongyan Tong

doi:10.1007/s00432-016-2331-0

Decitabine priming prior to low-dose chemotherapy improves patient outcomes in myelodysplastic syndromes-RAEB: a retrospective analysis vs. chemotherapy alone

J Cancer Res Clin Oncol. 2017 May;143(5):873-882. doi: 10.1007/s00432-016-2331-0. Epub 2017 Jan 20.

Authors

Li Ye^{1

2

3}, Yanling Ren^{1

2

3}, Xinping Zhou^{1

2

3}, Chen Mei^{1

2

3}, Liya Ma^{1

2

3}, Xingnong Ye^{1

2

3

4}, Juying Wei^{1

2}, Weilai Xu^{1

2}, Haitao Meng^{1

2}, Wenbin Qian^{1

2}, Wenyuan Mai^{1

2}, Yinjun Lou^{1

2}, Gaixiang Xu^{1

2}, Jiejing Qian^{1

2}, Yejiang Lou^{1

2}, Yingwan Luo^{1

2

3}, Lili Xie^{1

2

3}, Peipei Lin^{1

2

3}, Chao Hu^{1

2

3}, Jie Jin^{1

2}, Hongyan Tong^{5

6

7}

Affiliations

¹ Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang, China.
² Institute of Hematology, Zhejiang University, Hangzhou, 310009, Zhejiang, China.
³ Myelodysplastic Syndromes Diagnosis and Therapy Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang, China.
⁴ Department of Hematology, The Fourth Affiliated Hospital, College of Medicine, Zhejiang University, Yiwu, 322000, Zhejiang, China.
⁵ Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang, China. zjuhongyantong@163.com.
⁶ Institute of Hematology, Zhejiang University, Hangzhou, 310009, Zhejiang, China. zjuhongyantong@163.com.
⁷ Myelodysplastic Syndromes Diagnosis and Therapy Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang, China. zjuhongyantong@163.com.

Abstract

Purpose: The aim of this study was to examine whether decitabine priming prior to low-dose chemotherapeutic regimens could improve outcomes in patients with myelodysplastic syndromes-refractory anemia with excess of blasts (MDS-RAEB).

Methods: The current retrospective analysis included all MDS-RAEB patients receiving idarubicin/cytarabine (IA) or aclacinomycin/cytarabine (AA), with or without decitabine priming during a period from February 2010 to May 2015. Treatment response and toxicity were compared between patients receiving decitabine priming and those who did not. A panel of 6 MDS-related genes was examined using bone marrow specimens.

Results: A total of 81 patients were included in the analysis: 40 received decitabine priming prior to chemotherapy (decitabine priming group). The median follow-up was 10.9 months (IQR: 6.2-21.9). The rate of overall response (OR) and complete remission (CR) was significantly higher in the decitabine priming group than in the chemotherapy group (OR: 75.0 vs. 51.2%, p = 0.027; CR: 55.0 vs. 29.3%, p = 0.019). Overall survival (OS) did not differ significantly between the two groups (19.5 vs. 14.7 months, p = 0.082). In a subgroup analysis that included only patients at < 60 years of age, the CR rate in the decitabine priming group was significantly higher than in the chemotherapy group (65.5 vs. 31.0%, p = 0.009). Survival benefit of decitabine priming was apparent in patients at < 60 years of age (22.4 months with 95% CI of 6.7-38.1 vs. 14.7 months with 95% CI of 11.4-18.0 months in the chemotherapy group, p = 0.028), patients with intermediate and unfavorable karyotypes (22.4 months with 95% CI of 15.1-29.7 vs. 11.9 months with 95% CI of 4.0-19.8 months in the chemotherapy group, p = 0.042), and patients with mutated splicing factor genes (35.3 months with 95% CI of 21.4-49.2 vs. 17.8 months with 95% CI of 13.8-21.8 months in the chemotherapy group, p = 0.039). Grade 3-4 hematological and non-hematological toxicities were not significantly different between the two groups.

Conclusions: Decitabine priming prior to low-dose chemotherapy could improve treatment responses in patients with MDS-RAEB.

Keywords: Chemotherapy; Decitabine; Myelodysplastic syndromes.

Publication types

Comparative Study

MeSH terms

Aclarubicin / administration & dosage
Aclarubicin / analogs & derivatives
Adult
Anemia, Refractory, with Excess of Blasts / drug therapy*
Anemia, Refractory, with Excess of Blasts / genetics
Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
Azacitidine / administration & dosage
Azacitidine / analogs & derivatives
Cytarabine / administration & dosage
Decitabine
Dose-Response Relationship, Drug
Drug Administration Schedule
Female
Humans
Idarubicin / administration & dosage
Karyotype
Male
Middle Aged
Mutation
Retrospective Studies

Substances

aclacinomycins
Cytarabine
Aclarubicin
Decitabine
Azacitidine
Idarubicin