Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Oct 7:11:708727.
doi: 10.3389/fonc.2021.708727. eCollection 2021.

Reduced Intensity Conditioning Followed by Allogeneic Hematopoietic Stem Cell Transplantation Is a Good Choice for Acute Myeloid Leukemia and Myelodysplastic Syndrome: A Meta-Analysis of Randomized Controlled Trials

Yanzhi Song  1 , Zhichao Yin  1 , Jie Ding  2 , Tong Wu  1
Affiliations

Reduced Intensity Conditioning Followed by Allogeneic Hematopoietic Stem Cell Transplantation Is a Good Choice for Acute Myeloid Leukemia and Myelodysplastic Syndrome: A Meta-Analysis of Randomized Controlled Trials

Yanzhi Song et al. Front Oncol. .

Abstract

Background: Reduced intensity conditioning (RIC) before allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been reported to have the same overall survival (OS) as myeloablative conditioning (MAC) for patients with acute myeloid leukemia (AML) in complete remission (CR) and myelodysplastic syndrome (MDS). However, results from different studies are conflicting. Therefore, we conducted a systematic review and meta-analysis guided by PRISMA 2009 to confirm the efficacy and safety of RIC vs. MAC for AML in CR and MDS.

Methods: We search PubMed, Web of Science, Embase, Cochrane central, clinical trial registries and related websites, major conference proceedings, and field-related journals from January 1, 1980, to July 1, 2020, for studies comparing RIC with MAC before the first allo-HSCT in patients with AML in CR or MDS. Only randomized controlled trials (RCTs) were included. OS was the primary endpoint and generic inverse variance method was used to combine hazard ratio (HR) and 95% CI.

Results: We retrieved 7,770 records. Six RCTs with 1,413 participants (711 in RIC, 702 in MAC) were included. RIC had the same OS (HR = 0.95, 95% CI 0.64-1.4, p = 0.80) and cumulative incidence of relapse as MAC (HR = 1.18, 95% CI 0.88-1.59, p = 0.28). Furthermore, RIC significantly reduced non-relapse mortality more than total body irradiation/busulfan-based MAC (HR = 0.53, 95% CI 0.36-0.80, p = 0.002) and had similar long-term OS and graft failure as MAC.

Conclusion: RIC conditioning regimens are recommended as an adequate option of preparative treatment before allo-HSCT for patients with AML in CR or MDS.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=185436.

Keywords: acute myeloid leukemia; myelodysplastic syndrome; non-relapse mortality (NRM); overall survival; reduced intensity conditioning (RIC).

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flow diagram of screening studies for inclusion in systematic review. AML, acute myeloid leukemia; CR, complete remission; MDS, myelodysplastic syndrome; RCTs, randomized controlled trials; RIC, reduced intensity conditioning; MAC, myeloablative conditioning.
Figure 2
Figure 2
Results of meta-analyses of OS, CIR, and LFS endpoints. The forest plots showed that RIC had the same OS (A), CIR (B), and LFS (C) as MAC. RIC, reduced intensity conditioning; MAC, myeloablative conditioning; TBI, total body irradiation; Bu, busulfan.
Figure 3
Figure 3
Result of meta-analysis of long-term OS data. The forest plot showed that RIC had the same long-term OS as TBI/Bu-based MAC. OS, overall survival; RIC, reduced intensity conditioning; MAC, myeloablative conditioning; TBI, total body irradiation; Bu, busulfan.
Figure 4
Figure 4
Results of meta-analyses of NRM, aGVHD, and cGVHD endpoints. The forest plots showed that RIC significantly decreased NRM than TBI/Bu-based MAC (A). RIC showed a trend to decrease aGVHD, but it was not statistically significant (B). RIC had the same cGVHD as MAC (C). RIC, reduced intensity conditioning; MAC, myeloablative conditioning; TBI, total body irradiation; Bu, busulfan.
See this image and copyright information in PMC

References

    1. Horowitz MM, Gale RP, Sondel PM, Goldman JM, Kersey J, Kolb HJ, et al. . Graft-Versus-Leukemia Reactions After Bone Marrow Transplantation. Blood (1990) 75:555–62. doi: 10.1182/blood.V75.3.555.555 - DOI - PubMed
    1. Marks DI, Cullis JO, Ward KN, Lacey S, Syzdlo R, Hughes TP, et al. . Allogeneic Bone Marrow Transplantation for Chronic Myeloid Leukemia Using Sibling and Volunteer Unrelated Donors. A Comparison of Complications in the First 2 Years. Ann Intern Med (1993) 119:207–14. doi: 10.7326/0003-4819-119-3-199308010-00005 - DOI - PubMed
    1. Bacigalupo A, Ballen K, Rizzo D, Giralt S, Lazarus H, Ho V, et al. . Defining the Intensity of Conditioning Regimens: Working Definitions. Biol Blood Marrow Transplant (2009) 15:1628–33. doi: 10.1016/j.bbmt.2009.07.004 - DOI - PMC - PubMed
    1. Martino R, Iacobelli S, Brand R, Jansen T, van Biezen A, Finke J, et al. . Retrospective Comparison of Reduced-Intensity Conditioning and Conventional High-Dose Conditioning for Allogeneic Hematopoietic Stem Cell Transplantation Using HLA-Identical Sibling Donors in Myelodysplastic Syndromes. Blood (2006) 108:836–46. doi: 10.1182/blood-2005-11-4503 - DOI - PubMed
    1. Sugita J, Kagaya Y, Miyamoto T, Shibasaki Y, Nagafuji K, Ota S, et al. . Myeloablative and Reduced-Intensity Conditioning in HLA-Haploidentical Peripheral Blood Stem Cell Transplantation Using Post-Transplant Cyclophosphamide. Bone Marrow Transplant (2019) 54:432–41. doi: 10.1038/s41409-018-0279-1 - DOI - PubMed

Publication types