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.

Figure 1. Search strategy flow chart

The Embase, Pubmed, Cochrane and Abstract search, and the process of identifying relevant clinical trials for inclusion in the meta-analysis are shown. * the most updated report was included

Figure 2. Forrest plot of relapse-free survival (RFS) benefit of alloSCT in AML-CR1

The individual reports are indicated on the Y-axis. The summary effect estimate (HR) for individual study reports are indicated by black rectangles (the size of the rectangle is proportional to the study weight), with the lines representing 95% CI. The overall summary effect estimate (HR) and 95% CI are indicated by the diamond. Overall estimates after additional sensitivity and sub-group analyses are shown below. The corresponding values for number of patients at-risk in the donor versus no-donor arm and HR (95% CI) are indicated alongside. The number trials combined per pooled estimate are also indicated. * studies only reporting RFS endpoints

Figure 3. Forrest plot of overall survival (OS) benefit of alloSCT in AML-CR1

The individual reports are indicated on the Y-axis. The summary effect estimate (HR) for individual study reports are indicated by black rectangles (the size of the rectangle is proportional to the study weight), with the lines representing 95% CI. The overall summary effect estimate (HR) and 95% CI are indicated by the diamond below. Overall estimates after sensitivity and sub-group analyses are shown below. The corresponding values for number of patients at-risk in the donor versus no-donor arm and HR (95% CI) are indicated alongside. The number trials combined per pooled estimate are also indicated.