Research Paper Volume 13, Issue 8 pp 11120—11134
High-dose regimens of hypomethylating agents promote transfusion independence in IPSS lower-risk myelodysplastic syndromes: a meta-analysis of prospective studies
- 1 Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, China
Received: December 2, 2020 Accepted: January 14, 2021 Published: March 26, 2021
https://doi.org/10.18632/aging.202767How to Cite
Copyright: © 2021 Wan and Han. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
The hypomethylating agents (HMAs) azacytidine (AZA) and decitabine (DAC) are usually administered after the failure of erythropoietin-stimulating agents for lower-risk myelodysplastic syndromes (LR-MDS). However, it is unclear whether one of these HMAs has superior efficacy and safety. This was investigated in the present study by means of a meta-analysis of prospective studies published between January 1990 and July 2020 in PubMed, EMBASE, CENTRAL, and ClinicalTrials.gov databases; 19 studies with 1076 patients were included in the final analysis. The transfusion independence (TI) rate (66.7% [95% confidence interval: 41.7%–87.4%]) was higher with AZA 75 mg/m2/day for 7 days than with other regimens (all p<0.025). The proportion of patients with intermediate-1 risk influenced overall survival (p<0.05). There were no differences in treatment response, survival, and adverse event rates between patients treated with AZA (75 mg/m2/day for 5 days) and DAC (20 mg/m2/day for 3 days), although the latter group had a higher rate of grade 3/4 anemia (15.8% vs 0.0%; p<0.0001) and lower rate of diarrhea/constipation (6.9% vs 25.0%; p=0.002). Thus, both HMAs at high doses achieved reasonable response and TI rates with acceptable side effects, but did not prolong the overall survival in LR-MDS patients.
Abbreviations
5q-: deletion of 5q; AML: acute myeloid leukemia; ANC: absolute neutrophil count; AZA: azacytidine; BM: bone marrow; BSC: best supportive care; CR: complete remission; DAC: decitabine; EPO: erythropoietin; ESA: erythropoietin stimulating agents; Hb: hemoglobin; HI: hematologic improvement; HMAs: hypomethylating agents; IPSS: International Prognostic Scoring System; LR-MDS: lower-risk myelodysplastic syndromes; mCR: marrow complete remission; MDS: myelodysplastic syndromes; NHADE: adverse events; ORR: overall response rate; OS: overall survival; PR: partial remission; RA: refractory anemia; RAEB-1: refractory anemia with excess blasts-1; RARS: refractory anemia with ringed sideroblast; RCMD: refractory cytopenia with multilineage dysplasia; RCMD-RS: refractory cytopenia with multilineage dysplasia with ringed sideroblast; TD: transfusion-dependent; TI: transfusion independence.