Atypical Chronic Myeloid Leukemia Versus Myelodysplastic/Myeloproliferative Neoplasm-Unclassifiable
Jesse M Jaso, Bin Fu, L Jeffrey Medeiros, Sa A Wang. University of Texas MD Anderson Cancer Center, Houston, TX
Background: Myelodysplastic/Myeloproliferative neoplasms (MDS/MPN) in adults include chronic myelomonocytic leukemia (CMML), refractory anemia with ring sideroblasts with marked thrombocytosis (RARS-T), atypical chronic myeloid leukemia (aCML) and MDS/MPN-unclassifiable. In contrast to CMML and RARS-T, the clinical and genetic features of aCML and MDS/MPN-U are less well defined and they are often classified under the umbrella term of MDS/MPN. We present a series of 66 cases comparing the clinicopathologic features of aCML and MDS/MPN-U.
Design: We searched our hospital database for cases of MDS/MPN from 2003 to 2012. Clinical data were obtained from review of medical records. We excluded cases of CMML, RARS-T, cases with a documented history of MPN or MDS, and cases with molecular genetic abnormalities characteristic of well-defined entities. We used the 2008 WHO criteria for classification of aCML: marked leukocytosis, significant dysgranulopoiesis, and ≥10% myeloid precursors in peripheral blood (PB). Cases that failed to meet all three criteria were designated as MDS/MPN-U.
Results: From a denominator of 670 MDS/MPN patients, we identified 27 (4%) aCML and 39 (6%) MDS/MPN-U. The common features shared by aCML and MDS/MPN-U patients were older age (71 vs 72 years; range, 47-88); frequent organomegaly (48% vs 37%), elevated LDH (82% vs 73%), anemia (9.4 vs 9.6 g/dL), myelofibrosis (> MF-1) (37% vs 39%) and karyotypic abnormalities (44% vs 39%). aCML patients, however, had significantly higher WBC, ANC, PB blasts and myeloid precursors, worse thrombocytopenia, and a higher bone marrow myeloid:erythroid ratio. JAK-2 V617F mutation was detected in 13/49 cases (26%) showing no difference between aCML and MDS/MPN-U (17% vs 32%, p=0.322), but correlated with myelofibrosis (≤MF-1 vs >MF-1, 55% vs 9%, p<0.001). RAS and JAK-2 V617 mutations were mutually exclusive, and a higher frequency of RAS mutation was detected in aCML (8/18 vs 2/26 p=0.008). With a median follow-up of 34 months, aCML patients showed a shorter disease specific survival than MDS/MPN-U patients (32 vs 41 months, p=0.029).
Conclusions: aCML and MDS/MPN-U are infrequent subtypes of MDS/MPN in adults. aCML and MDS/MPN-U share many overlapping features; however, the WHO criteria for aCML define a subgroup of MDS/MPN characterized by a prominent proliferation of the granulocytic lineage with marked dysgranulopoiesis, high frequency of RAS mutations, and an inferior outcome.
Tuesday, March 5, 2013 11:15 AM
Proffered Papers: Section C, Tuesday Morning