Prognostic Factors in Unfavourable-Risk Acute Myeloid Leukemia in the Absence of Monosomal Karyotype
Macy Chen, Joseph Brandwein, Kenneth J Craddock, Hong Chang. University Health Network, University of Toronto, Toronto, Canada
Background: Cytogenetics has been routinely utilized to stratify AML patients into favourable, intermediate, and high risk groups for therapeutic response and survival. Recently, the presence of monosomal karyotype (MK+), defined as two or more autosomal monosomies or one monosomy with structural aberrations, was found to be associated with extremely poor clinical outcome in AML patients with unfavourable-risk cytogenetics. However, patients without MK (MK-) constitute a sizable subset of unfavourable- risk AML but have a heterogeneous clinical course. The prognostic factors in this subgroup remained to be elucidated.
Design: We retrospectively examined 1656 adult de novo non-promyelocytic AML patients treated at University Health Network from 2000 to 2010. Multi-parameter flow cytometric immunophenotyping and conventional cytogenetics were performed for all at diagnosis. Patients with normal, missing/failed karyotype or favourable, intermediate risk cytogenetics were excluded. There were 233 patients classified as unfavourable-risk cytogenetics group by MRC criteria, and further analyzed for the monosomy status and correlated with their immunophenotype, clinical features, and survival outcomes.
Results: The 233 patients had a median age of 62 years (range 18-90), and overall survival (OS) of 8.2 months (95%CI: 6.0–10.4 months). MK+ patients (n=121) had significantly lower complete remission (CR) rate (p=0.009), shorter event-free survival (EFS, p<0.0001) and OS (p<0.0001) than those without MK. Among MK- patients (n=112, 48%), co-expression of CD11b and CD15 was present in 39% of the patients and was associated with significantly shorter OS (median 6.6 vs 17.7 months, p=0.008). None of the other immunophenotypic markers significantly impacted clinical outcome in this AML subgroup. In addition, older MK- patients (≥60 yrs) had poorer CR rate, EFS and OS (p=0.036, p=0.016, p=0.002, respectively). On multivariate analysis, age≥60 (HR=2.46, 95%CI: 1.42-4.26, p=0.001), CD11b+/CD15+ (HR=2.07, 95%CI: 1.21-3.55, p=0.008) and WBC>30 (HR=1.94, 95%CI: 1.10-3.41, p=0.022) emerged as independent prognostic factors for shorter OS in MK- AML. However, the presence of complex karyotype (≥3 genetic abnormalities) did not influence the survival in this cohort.
Conclusions: Our analysis validated the adverse influence of MK in AML patients and identified the poor prognostic impact of CD11b/CD15 co-expression in MK- AML with unfavorable cytogenetics. Thus, this study further strengthened the risk-stratification of unfavourable risk AML patients by incorporating immunophenotype as a risk parameter.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 222, Tuesday Morning