Predictive Value of Cytogenetics on Outcomes of Stem Cell Transplantation in Acute Myeloid Leukemia.

Abstract

Cytogenetic analysis performed at diagnosis is generally recognized as the single most valuable prognostic factor in AML. Several reports have suggested that cytogenetic characteristics present at diagnosis are associated not only with response to induction therapy for adult AML but also with the outcomes of postremission therapy. Our aim in this study was to examine the relationship of disease karyotypes at diagnosis with the outcomes of stem cell transplantation (SCT) as a postremission therapy in the first remission (CR1) of AML. To describe the differences and similarities used by different cooperative groups and to guide future investigations, the cytogenetic data presented in this study were coded and analyzed using two different classification schemes, SWOG and MRC. Forty-six AML patients younger than 56 years old who had undergone allogeneic or autologous SCT as postremission therapy were analyzed. Patients were categorized into favorable, intermediate, unfavorable, and unknown cytogenetic risk groups based on pretreatment karyotypes according to SWOG and MRC criteria. Prior to SCT, all patients received induction and consolidation chemotherapy consisting of idarubicin and cytarabine. Eight patients died during the median follow-up of 37.8 months (range, 7.6–91.8). The 3-year disease-free survival (DFS) and overall survival (OS) rates were 70.9% and 76.2% for all patients (n = 46). In univariate and multivariate analyses, cytogenetic risk status as grouped by the SWOG criteria was a significant prognostic factor for OS in patients with AML in CR1 who underwent SCT as postremission therapy (P = 0.017, P = 0.009). These data suggest that the pretreatment cytogenetic risk factor is the most valuable prognostic factor for OS in patients with AML in CR1 who undergo SCT as a postremission therapy. In particular, the SWOG criteria are superior in predicting OS and survival in our analysis. However, the unknown risk group in the SWOG criteria and the intermediate risk group in the MRC criteria are heterogeneous, and analyses that are more extensive are required. What is clearly needed is a generally accepted cytogenetic classification system and a leukemia cytogenetic database to provide prognostic scoring and real-time data updates, principally for the less frequent and secondary cytogenetic aberrations. Since the current analysis contains only data from patients who received SCT, this analysis has the possibility of being biased due to selection of patients with good performance and the exclusion of those with early relapses. However, the strengths of this trial included its well-defined eligibility criteria, including pretreatment cytogenetic studies, uniform treatment regimens for induction and postremission therapies, and the time between CR1 and SCT.