Allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission: systematic review and meta-analysis of prospective clinical trials.

Abstract

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.

• Authors: John Koreth, Richard Schlenk, Kenneth J Kopecky, Sumihisa Honda, Jorge Sierra, Benjamin J Djulbegovic, Martha Wadleigh, Daniel J DeAngelo, Richard M Stone, Hisashi Sakamaki, Frederick R Appelbaum, Hartmut Döhner, Joseph H Antin, Robert J Soiffer, Corey Cutler
• Journal: JAMA (JAMA) Vol. 301 Issue 22 Pg. 2349-61 (Jun 10 2009) ISSN: 1538-3598 [Electronic] United States
• PMID: 19509382 (Publication Type: Journal Article, Meta-Analysis, Review, Systematic Review)

Chemical References

• Antineoplastic Agents

Topics

• Antineoplastic Agents (therapeutic use)
• Clinical Trials as Topic
• Humans
• Leukemia, Myeloid, Acute (mortality, therapy)
• Remission Induction
• Risk Assessment
• Stem Cell Transplantation
• Survival Analysis
• Transplantation, Homologous