Adult Acute Myeloid Leukemia Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Adult Acute Myeloid Leukemia in Remission
A common clinical trial design used to evaluate the benefit of allogeneic transplant as consolidation therapy for AML in first remission is the so-called donor-no donor comparison. In this design, newly diagnosed AML patients who achieve a complete remission (CR1), have one or more siblings, and are deemed medically eligible for allogeneic transplant undergo HLA typing. If a sibling donor is identified, the patient is allocated to the transplantation arm. Analysis of outcome is by intention to treat; that is, patients assigned to the donor arm who do not receive a transplant are grouped in the analysis with the patients who did actually receive a transplant. Relapse-free survival (RFS) is the usual endpoint for this type of trial. Overall survival (OS) from the time of diagnosis is less frequently reported in these trials. Results of these trials have been mixed, with some trials showing a clear benefit across all cytogenetic subgroups, and others showing no benefit.
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 to autologous transplant (6 trials) or to 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 CR1. 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 CR1.
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 CR1 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]