Investigators attempted to address this issue with a meta-analysis using data from 18 separate prospective trials of AML patients using the donor-no donor design, with data from an additional six trials included for sensitivity analysis. The trials included in this meta-analysis enrolled adult patients aged 60 and younger during the years 1982 to 2006. Median follow-up ranged from 42 months to 142 months. Preparative regimens were similar among the different trials. Allogeneic transplant was compared with autologous transplant (6 trials) or with a variety of consolidation chemotherapy regimens, with high-dose cytarabine being the most common.
Treatment-related mortality ranged from 5% to 42% in the donor groups compared with 3% to 27% in the no-donor group. Of 18 trials reporting RFS across all cytogenetic risk groups, the combined hazard ratio (HR) for overall RFS benefit with allogeneic transplant was 0.80, indicating a statistically significant reduction in death or relapse in a first CR. Of the 15 trials reporting OS across all cytogenetic risk groups, the combined HR for OS was 0.90, again indicating a statistically significant reduction in death or relapse in a first CR.
In subgroup analysis according to cytogenetic risk category, there was no RFS or OS benefit of allogeneic transplant for patients with good-risk AML (RFS: HR, 1.07; 95% confidence interval [CI], 0.83–1.38; P = .59; OS: HR, 1.06; 95% CI, 0.64–1.76; P = .81). However, a transplant benefit was seen for patients with intermediate (RFS: HR, 0.83; 95% CI, 0.74–0.93; P < .01; OS: HR, 0.84; 95% CI, 0.71–0.99; P = .03) or poor-risk cytogenetics (RFS: HR, 0.73; 95% CI, 0.59–0.90; P < .01; OS: HR, 0.60; 95% CI, 0.40–0.90; P = .01). The conclusion from this meta-analysis was that allogeneic transplant from a sibling donor in a first CR is justified on the basis of improved RFS and OS for patients with intermediate- or poor-risk, but not good-risk, cytogenetics.[Level of evidence: 2A]
An important caveat to this analysis is that induction and postremission strategies for AML among studies included in the meta-analysis were not uniform; nor were definitions of cytogenetic risk groups uniform. This may have resulted in inferior survival rates among chemotherapy-only treated patients. Most U.S. leukemia physicians agree that transplantation should be offered to AML patients in first CR in the setting of poor-risk cytogenetics and should not be offered to patients in first CR with good-risk cytogenetics.