J Cancer 2020; 11(17):5223-5235. doi:10.7150/jca.46081

Research Paper

Reduced-intensity versus Myeloablative Conditioning Regimens for Younger Adults with Acute Myeloid Leukemia and Myelodysplastic Syndrome: A systematic review and meta-analysis

Shengling Ma1*, Wei Shi1,2*, Ziying Li1, Liang Tang1, Huafang Wang1, Linghui Xia1, Yu Hu1✉

1. Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
2. Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
*These authors contributed equally to this work.

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Citation:
Ma S, Shi W, Li Z, Tang L, Wang H, Xia L, Hu Y. Reduced-intensity versus Myeloablative Conditioning Regimens for Younger Adults with Acute Myeloid Leukemia and Myelodysplastic Syndrome: A systematic review and meta-analysis. J Cancer 2020; 11(17):5223-5235. doi:10.7150/jca.46081. Available from https://www.jcancer.org/v11p5223.htm

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Abstract

Background: Historically, reduced-intensity conditioning (RIC) was recommended to be performed for older patients who were considered ineligible for myeloablative conditioning (MAC) before allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the evidence regarding the optimal conditioning intensity in younger patients with AML or MDS is weak and contradictory.

Methods: PubMed, Medline, Embase, and other online sources were searched from the initial period to February 25, 2020. Odds ratios and 95% confidence intervals were calculated to estimate pooling effects.

Results: Four randomized controlled trials (RCTs) about conditioning intensity involving 633 patients were included. There were no significant differences of 1/2/4/5 years progression-free survival (PFS) and relapse incidence (RI) between two conditioning intensities. Overall survival (OS) was similar at 1/2/4 years, but patients receiving RIC had a higher OS at 5 years. Additionally, RIC were associated with lower non-relapse mortality, less grade II-IV and grade III-IV acute graft-versus-host disease (GVHD), and lower incidence of chronic GVHD compared with MAC regimens. Subgroup analysis showed similar OS and RI for AML patients, and there was a trend towards lower NRM and grade II-IV aGVHD in RIC group. Available data for MDS indicated that OS, PFS, and RI were comparable. For intermediate-risk patients, there was no evidence that RIC is inferior to MAC. However, for high-risk patients, MAC tends to perform better.

Conclusions: Based on the above results, it might be concluded that RIC is a feasible treatment option for adults with AML or MDS younger than 66 years, particularly those with intermediate-risk disease. Future RCTs incorporating of risk stratifications are warranted to guide the optimal decision under certain conditions.

Keywords: myeloablative, stem cell, acute myeloid leukemia