Acute Myeloid Leukemia Arising from Chronic Myelomonocytic Leukemia Has Poor Prognosis and High Incidence of Normal Karyotype and NPM1 Mutation
Elizabeth Courville, Yue Wu, Jihen Kourda, Jillian Brockmann, Laurence de Leval, Attilio Orazi, Robert Hasserjian. Massachusetts General Hospital, Boston; Weill Cornell Medical College, New York; Institut Universitaire de Pathologie, Lausanne, Switzerland
Background: Chronic myelomonocytic leukemia (CMML) progresses to acute myeloid leukemia (AML) in 15-30% of patients; these cases are classified as AML with myelodysplasia-related changes (AML-MRC), an aggressive AML subtype in the current WHO Classification. However, the clinicopathologic features of AML arising from CMML have not been well-described.
Design: We reviewed 29 cases of AML arising in patients with a history of CMML (AML ex CMML) from 3 institutions. We reviewed the clincopathologic features, cytogenetics, and NPM1 mutation status (by PCR and/or NPM1 immunostaining) of the CMML and AML cases and evaluated patient outcome. For comparison, we reviewed 14 cases of CMML that did not transform to AML over a followup period of ≥ 12 months, 21 cases of AML arising from myelodysplastic syndromes (AML ex MDS), and 120 de novo AML cases.
Results: The CMML patients who progressed to AML were younger (p=0.002) and had higher bone marrow blast+monocyte counts (p=0.04), increased bone marrow reticulin grade (p=0.04), and greater erythroid dysplasia (p=0.01) compared to the non-progressors. 11/20 AML ex CMML cases were myelomonocytic type (M4), while 4/20 were monocytic (M5) and 5/20 were myeloid with maturation (M2). 14/21 (67%) of the AML ex CMML had normal karyotype compared with 7/17 (41%) of AML ex MDS; only 2/18 (11%) AML ex CMML cases showed karyotypic progression. 5/24 (17%) of the AML ex CMML, including 4/11 (36%) who progressed to AML in <12 months, had NPM1 mutation, compared with 0/10 CMML patients who did not progress (p=0.02, AML progression in <12 months versus others). In 3 NPM1 mutated cases, the mutation was present in the AML but not the CMML, suggesting secondary acquisition of this mutation coincident with AML progression; this contrasts with NPM1 mutations occurring in de novo AML, which appear to be early "founder" events in leukemogenesis. Median overall survival (OS) of the AML ex CMML patients was 6 months, similar to that of patients with AML ex MDS (8 months). AML ex CMML patients with normal karyotype had inferior OS (median 10 months) to normal karyotype de novo AML patients (28 months)(p= 0.04).
Conclusions: Our findings indicate that most cases of AML arising from CMML have normal karyotype, but show an inferior outcome compared with de novo AML and similar to AML post-MDS, validating their classification as AML-MRC. An NPM1 mutation was associated with cases that rapidly progressed to AML.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 237, Monday Morning