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Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia in First Complete Remission Systematic Review and Meta-analysis of Prospective Clinical Trials

John Koreth, MBBS, DPhil; Richard Schlenk, MD; Kenneth J. Kopecky, PhD; Sumihisa Honda, PhD; Jorge Sierra, MD, PhD; Benjamin J. Djulbegovic, MD, PhD; Martha Wadleigh, MD; Daniel J. DeAngelo, MD, PhD; Richard M. Stone, MD; Hisashi Sakamaki, MD, PhD; Frederick R. Appelbaum, MD; Hartmut Döhner, MD; Joseph H. Antin, MD; Robert J. Soiffer, MD; Corey Cutler, MD, MPH, FRCPC
JAMA. 2009;301(22):2349-2361. doi:10.1001/jama.2009.813.
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Context The optimal treatment of acute myeloid leukemia (AML) in first complete remission (CR1) is uncertain. Current consensus, based on cytogenetic risk, recommends myeloablative allogeneic stem cell transplantation (SCT) for poor-risk but not for good-risk AML. Allogeneic SCT, autologous transplantation, and consolidation chemotherapy are considered of equivalent benefit for intermediate-risk AML.

Objective To quantify relapse-free survival (RFS) and overall survival benefit of allogeneic SCT for AML in CR1 overall and also for good-, intermediate-, and poor-risk AML.

Methods Systematic review and meta-analysis of prospective trials evaluating allogeneic SCT vs nonallogeneic SCT therapies for AML in CR1. The search used the combined search terms allogeneic; acut* and leukem*/leukaem*/leucem*/leucaem*/aml; myelo* or nonlympho* in the PubMed, Embase, and Cochrane Registry of Controlled Trials databases in March 2009. The search identified 1712 articles.

Study Selection Prospective trials assigning adult patients with AML in CR1 to undergo allogeneic SCT vs nonallogeneic SCT treatment(s) based on donor availability and trials reporting RFS and/or overall survival outcomes on an intention-to-treat, donor vs no-donor basis were identified.

Data Extraction Two reviewers independently extracted study characteristics, interventions, and outcomes. Hazard ratios (HRs) with 95% confidence intervals (CIs) were determined.

Data Synthesis Overall, 24 trials and 6007 patients were analyzed (5951 patients in RFS analyses and 5606 patients in overall survival analyses); 3638 patients were analyzed by cytogenetic risk (547, 2499, and 592 with good-, intermediate-, and poor-risk AML, respectively). Interstudy heterogeneity was not significant. Fixed-effects meta-analysis was performed. Compared with nonallogeneic SCT, the HR of relapse or death with allogeneic SCT for AML in CR1 was 0.80 (95% CI, 0.74-0.86). Significant RFS benefit of allogeneic SCT was documented for poor-risk (HR, 0.69; 95% CI, 0.57-0.84) and intermediate-risk AML (HR, 0.76; 95% CI, 0.68-0.85) but not for good-risk AML (HR, 1.06; 95% CI, 0.80-1.42). The HR of death with allogeneic SCT for AML in CR1 was 0.90 (95% CI, 0.82-0.97). Significant overall survival benefit with allogeneic SCT was documented for poor-risk (HR, 0.73; 95% CI, 0.59-0.90) and intermediate-risk AML (HR, 0.83; 95% CI, 0.74-0.93) but not for good-risk AML (HR, 1.07; 95% CI, 0.83-1.38).

Conclusion Compared with nonallogeneic SCT therapies, allogeneic SCT has significant RFS and overall survival benefit for intermediate- and poor-risk AML but not for good-risk AML in first complete remission.

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Figure 1. Search Strategy
Graphic Jump Location

ITT indicates intention-to-treat; SCT, stem cell transplantation.
aThe most updated report was included.

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Figure 2. Relapse-Free Survival (RFS) Benefit of Allogeneic SCT for AML in First Complete Remission
Graphic Jump Location

Black rectangles indicate summary effects estimates (hazard ratios [HRs]) for individual study reports. Sizes of data markers are proportional to the study weights. Error bars indicate 95% confidence intervals (CIs). AML indicates acute myeloid leukemia; RFS, relapse-free survival.
aStudies only reporting RFS end points.

Place holder to copy figure label and caption
Figure 3. Overall Survival Benefit of Allogeneic SCT for AML in First Complete Remission
Graphic Jump Location

Black rectangles indicate summary effects estimates (hazard ratios [HRs]) for individual study reports. Sizes of data markers are proportional to the study weights. Error bars indicate 95% confidence intervals (CIs). AML indicates acute myeloid leukemia.

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