Acute Myeloid Leukemia with Myelodysplasia-Related Changes as Defined by the 2008 WHO Classification System
OK Weinberg, M Seetharam, L Ren, L Ma, K Seo, J Merker, J Gotlib, J Zehnder, DA Arber. Stanford University, Stanford, CA
Background: The 2008 WHO classification system has created a new category Acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) that includes 1) AML arising from myelodysplastic syndrome (MDS), 2) AML with MDS-related cytogenetic abnormalities and/or 3) AML with multilineage dysplasia. The goal of this study is to characterize the newly defined AML-MRC group.
Design: One-hundred AML patients, including 57 males and 43 females diagnosed at Stanford University, were tested for NPM, FLT3 (ITD and D835) and CEBPA mutations and stratified into cytogenetic risk groups. Overall survival (OS), progression free survival (PFS) and complete remission (CR) rates were retrospectively determined and compared using Kaplan-Meier and multivariate Cox proportional hazards regression.
Results: Using the 2008 WHO criteria, there were 48 AML-MRC (16 with prior MDS; 14 with MDS-related cytogenetics; 32 with multilineage dysplasia), 40 AML not otherwise specified (AML-NOS), 9 AML with either t(8;21), inv(16) or t(15;17) and 3 therapy-related AMLs. Clinically, patients with AML-MRC, compared to AML-NOS, were significantly older (59 vs 51 years, p=0.014) and presented with lower hematocrit (28 vs 33%, p=0.014). AML-MRC, compared to AML-NOS, was also associated with unfavorable cytogenetics (14/48 vs 3/36, p=0.014) and a lower frequency of CEBPA mutations (0/46 vs 7/40, p=0.001), but no difference in NPM1 or FLT3 mutations. Patients with AML-MRC had significantly worse OS, PFS and CR compared to AML-NOS (all p<0.0001). To evaluate the significance of multilineage dysplasia, 14 patients with unfavorable cytogenetics were excluded from the AML-MRC group and the remaining patients with AML-MRC still had worse outcomes compared to all AML-NOS (OS p=0.013; PFS p=0.012; CR p=0.008). Within the AML-MRC group, low platelets (<20K/m3), FLT3-D835 and MDS-related cytogenetics correlated with worse OS (p=0.045, p=0.026, p=0.002). Multivariate Cox proportional hazard analysis performed on all cases identified unfavorable cytogenetics, age >60y, FLT3-ITD and AML-MRC status as predictors of worse OS (hazard ratios: 2.82, 2.11, 1.98, 1.92).
Conclusions: The newly defined WHO category of AML-MRC, when compared to AML-NOS, is significantly associated with advanced age, lower hematocrit, lack of CEPBA mutation, presence of high risk cytogenetics and worse clinical outcome. The poor overall survival of this group in all AML, independent of age or cytogenetic risk group, supports the clinical relevance of AML-MRC.
Tuesday, March 10, 2009 1:45 PM
Platform Session: Section D, Tuesday Afternoon