Prognostic Impact of Immunophenotyping for Normal Karyotype Acute Myeloid Leukemia in the Absence of FLT3-ITD Mutation
A Jiang, H Jiang, W Xu, J Brandwein, S Kamel-Reid, H Chang. University of Toronto, Toronto, Canada
Background: Patients with normal karyotype acute myeloid leukemia (NK-AML) comprise the largest subgroup which is considered to have an intermediate prognosis. Recent studies indicate that the FLT3-ITD mutation is the adverse risk factor for NK-AML. However, outcomes are still very heterogeneous among those patients without FLT3-ITD mutations. The objective of this study is to identify risk factors to further stratify patients with NK-AML in the absence of FLT3-ITD mutation.
Design: We evaluated a cohort of 196 NK-AML patients diagnosed and treated at our institute. Immunophenotype was assessed by multiparameter flow cytometry; FLT3-ITD, FLT3-TKD and Nucleophosmin genes (NPM1) mutation status were detected by RT-PCR. Patient's clinical and laboratory data were collected by chart review.
Results: FLT3-ITD was found in 18 (15%) of 118 evaluable cases. Consistent with previous reports, FLT3-ITD was associated with higher WBC counts (>30 billion/liter), NPM1 mutations, absence of CD34 expression and shorter relapse free (RFS), event free (EFS) and overall survivals (OS). We then focused on a subgroup of 100 patients who do not have the FLT3-ITD mutations; CD34 and CD56 were expressed in 57% and 11% cases respectively. Univariate analysis identified that CD34 expression and high WBC counts (>30) were associated with a worse RFS (12.0 months vs. not reached, p=0.025; and 12.4 months vs. not reached, p=0.031, respectively); CD34 expression and older age (> 60) were associated with a shorter EFS (5.8 vs. 18.3 months, p=0.002; and 9.4 vs. 13.6 months, p=0.02, respectively); and CD56 expression conferred a shorter OS (14.1 vs. 31.8 months, p=0.034). Multivariate analysis adjusting above risk factors revealed that CD34 expression and high WBC count (>30) were independent adverse factors for RFS (p=0.005 and 0.006, respectively), while CD34 and CD56 expression were independent adverse factors for both EFS (p=0.001 and 0.047, respectively) and OS (p=0.043 and 0.017, respectively). Other phenotypic markers such as CD7, CD15, CD11b, CD13/CD33, HLA-DR did not affect the outcome in this cohort.
Conclusions: Our data suggest that in the absence of FLT3-ITD, CD34 and CD56 expressions predict an adverse outcome in patients of NK-AML. Immunophenotyping may be a valuable tool for risk stratification of NK-AML patients who do not have the FLT3-ITD mutation. Larger prospective studies are warranted to confirm our findings.
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 185, Wednesday Afternoon