title: Clinicopathologic analysis of acute myeloid leukemia arising from chronic myelomonocytic leukemia.
abstract: Acute myeloid leukemia arising from chronic myelomonocytic leukemia is currently classified as acute myeloid leukemia with myelodysplasia-related changes, a high-risk subtype. However, the specific features of these cases have not been well described. We studied 38 patients with chronic myelomonocytic leukemia who progressed to acute myeloid leukemia. We compared the clinicopathologic and genetic features of these cases with 180 patients with de novo acute myeloid leukemia and 34 patients with acute myeloid leukemia following myelodysplastic syndromes. We also examined features associated with progression from chronic myelomonocytic leukemia to acute myeloid leukemia by comparing the progressed chronic myelomonocytic leukemia cases with a cohort of chronic myelomonocytic leukemia cases that did not transform to acute myeloid leukemia. Higher white blood cell count, marrow cellularity, karyotype risk score, and Revised International Prognostic Scoring System score were associated with more rapid progression from chronic myelomonocytic leukemia to acute myeloid leukemia. Patients with acute myeloid leukemia ex chronic myelomonocytic leukemia were older (P<0.01) and less likely to receive aggressive treatment (P=0.02) than de novo acute myeloid leukemia patients. Most cases showed monocytic differentiation and fell into the intermediate acute myeloid leukemia karyotype risk group; 55% had normal karyotype and 17% had NPM1 mutation. Median overall survival was 6 months, which was inferior to de novo acute myeloid leukemia (17 months, P=0.002) but similar to post myelodysplastic syndrome acute myeloid leukemia. On multivariate analysis of all acute myeloid leukemia patients, only age and karyotype were independent prognostic variables for overall survival. Our findings indicate that acute myeloid leukemia following chronic myelomonocytic leukemia displays aggressive behavior and support placement of these cases within the category of acute myeloid leukemia with myelodysplasia-related changes. The poor prognosis of these patients may be related to an older population and lack of favorable-prognosis karyotypes that characterize many de novo acute myeloid leukemia cases.
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Courville
authors.forename: Yue
authors.initials: Y
authors.lastname: Wu
authors.forename: Jihen
authors.initials: J
authors.lastname: Kourda
authors.forename: Christine G
authors.initials: CG
authors.lastname: Roth
authors.forename: Jillian
authors.initials: J
authors.lastname: Brockmann
authors.forename: Alona
authors.initials: A
authors.lastname: Muzikansky
authors.forename: Amir T
authors.initials: AT
authors.lastname: Fathi
authors.forename: Laurence
authors.initials: L
authors.lastname: de Leval
authors.forename: Attilio
authors.initials: A
authors.lastname: Orazi
authors.forename: Robert P
authors.initials: RP
authors.lastname: Hasserjian
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000473:pathology; D001856:Bone Marrow Examination; D002454:Cell Differentiation; D016009:Chi-Square Distribution; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D015477:Leukemia, Myelomonocytic, Chronic / Q000235:genetics / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000473:pathology; D015999:Multivariate Analysis; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics; D000090243:Nucleophosmin; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D013557:Switzerland; D014481:United States; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3