Prognostic Impact of Immunophenotyping in Elderly Acute Myeloid Leukemia with Normal Karyotype.
Allan Jiang, Joseph Brandwein, Hong Chang. University Health Network, Toronto, Canada
Background: Acute myeloid leukemia (AML) patients 60 years and older have a particularly short survival, and thus are difficult to treat. Prognostic markers are required to better stratify these patients. Two recent studies have shown that parameters such as CD34 expression and complex karyotype correlated with the adverse outcome of elderly AML. However, little is known about prognostic factors in elderly normal karyotype (NK) AML, the largest AML cytogenetic risk group with a high degree of clinical heterogeneity. We therefore evaluated the prognostic relevance of immunophenotypic markers, in the context of genetic and clinical features, on a large cohort of elderly NK-AML patients.
Design: Of 518 elderly patients diagnosed with de novo AML between Jan 2005 and Mar 2010 at UHN, 203 were uniformly treated with cytosine arabinoside and daunorubicin as per institutional protocol. 103 of these patients were classified as NK-AML, and were entered into our study. FLT3 and NPM1 status were evaluated by multiplex RT-PCR, and immunophenotypes were determined by multi-parameter flow cytometry.
Results: CD7 was expressed in 23 of 97 (24%) patients; CD15 in 47 of 99 (47%); CD34 in 50 of 100 (50%), CD56 in 14 of 97 (14%); and HLA-DR in 71 of 98 (72%). 63 (61%) patients achieved complete remission (CR) following induction therapy; the median event-free survival (EFS) was 8.2 months, and the median overall survival (OS) was 15.4 months. CD56 positivity correlated with lower CR rate (29% vs. 67%, p=0.008). Patients expressing CD56 (median 1.1 vs. 8.8 months, p=0.021) and CD34 (median 6.1 vs. 10.5 months, p=0.008) had shorter EFS, as did patients lacking CD15 (median 7.1 vs. 9.4 months, p=0.050). In addition, leukocyte count >30x109/L (median 12.1 vs. 18.3 months, p=0.039), FLT3-ITD mutation (median 10.1 vs. 26.6 months, p=0.002), and CD34 expression (median 13.0 vs. 20.5 months, p=0.042) conferred a shorter OS. Other parameters such as age, FAB subtype, CD7, and HLA-DR, did not significantly impact outcome. Multivariate analysis adjusting for leukocyte count, CD15, CD34, and CD56 expression revealed that CD34 is an independent predictor of lower CR rate (HR=0.21, p=0.003), EFS (HR=2.17, p=0.003), and OS (HR=1.84, p=0.026). CD56 predicted an inferior CR rate (HR=0.06, p<0.001) and EFS (HR=3.00, p=0.002), while high leukocyte count predicted shorter OS (HR=1.95, p=0.012).
Conclusions: Our data indicate that CD34, CD56 and high leukocyte count are adverse prognostic factors in elderly NK-AML. Further studies are warranted to confirm the impact of these immunophenotypes, and may lead to a better therapeutic management of elderly AML.
Monday, February 28, 2011 1:00 PM
Poster Session II # 187, Monday Afternoon