Reduced-intensity and myeloablative conditioning allogeneic hematopoietic stem cell transplantation in patients with acute myeloid leukemia and myelodysplastic syndrome: a meta-analysis and systematic review.

BACKGROUND: We performed a systematic review and meta-analysis to compare the clinical outcomes and toxicity of reduced-intensity conditioning (RIC) and myeloablative conditioning (MAC) allogeneic hematopoietic stem cell transplantation (alloHSCT) in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).

EVIDENCE ACQUISITION: A comprehensive PubMed and Embase search was performed using the following keywords: "reduced-intensity", "myeloablative", "AML", and "MDS". The primary endpoints were overall survival (OS) and event-free survival (EFS), and the secondary endpoints were relapse incidence (RI), non-relapse mortality (NRM), grade II-IV acute graft-versus-host disease (aGVHD), and chronic GVHD (cGVHD).

RESULTS: Eight studies (2 prospective and 6 retrospective) involving 6464 patients who received RIC (n = 1571) or MAC (n = 4893) alloHSCT were included in the analysis. Median age and the number of patients with low hematopoietic cell transplantation-specific comorbidity index scores and who received ex vivo or in vivo T cell depletion were higher in the RIC arm than in the MAC arm. Significant heterogeneity was not found among the studies for any of the endpoints except for grade II-IV aGVHD. OS (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.84-1.08; p = 0.47) and EFS (OR, 0.88; 95% CI, 0.77-1.00; p = 0.05) were similar in the RIC and MAC arms, whereas RI (OR, 1.41; 95% CI, 1.24-1.59; p < 0.00001) was higher in the RIC arm than in the MAC arm. The incidence of grade II-IV aGVHD (OR, 0.59; 95% CI, 0.36-0.96; p = 0.03) was lower in the RIC arm than in the MAC arm; however, NRM (OR, 0.99; 95% CI, 0.87-1.13; p = 0.85), total cGVHD (OR, 1.10; 95% CI, 0.88-1.38; p = 0.38), and extensive cGVHD (OR, 1.01; 95% CI, 0.75-1.37; p = 0.95) were not significantly different between the two arms.

CONCLUSION: RIC alloHSCT may be an effective treatment strategy for AML/MDS patients who are not suitable candidates for MAC alloHSCT. However, heterogeneity in baseline patient characteristics and treatment protocols may have influenced the outcomes of RIC alloHSCT in our analysis. Future randomized controlled trials are needed to confirm our findings.