title: Reproducibility and prognostic significance of morphologic dysplasia in de novo acute myeloid leukemia.
abstract: The 2008 WHO classification of acute myeloid leukemia includes a category of acute myeloid leukemia with myelodysplasia-related changes; however, the significance of multilineage dysplasia alone is controversial and its reproducibility has not been evaluated in acute myeloid leukemia. We performed an in-depth analysis of morphologic dysplasia in 159 de novo acute myeloid leukemia cases lacking myelodysplasia-related cytogenetic abnormalities. Using the 2008 WHO criteria, there were 89 acute myeloid leukemia-not otherwise specified (56%) and 43 acute myeloid leukemia with myelodysplasia-related changes (27%), while 27 cases were ambiguous as to myelodysplasia-related changes status due to limited maturing cells (acute myeloid leukemia-not evaluable, 17%). On multivariable analysis, neither acute myeloid leukemia with myelodysplasia-related changes nor acute myeloid leukemia-not evaluable showed significantly different event-free survival compared with acute myeloid leukemia-not otherwise specified in the 137 patients treated with induction chemotherapy. When individual dysplastic features were analyzed, only micromegakaryocytes and hypogranulated myeloid cells emerged as factors significantly associated with shorter event-free survival in a multivariable analysis that included the other significant covariates of age, white blood count, platelet count, abnormal karyotype and stem-cell transplantation. Our findings indicate that the current 2008 WHO definition of multilineage dysplasia in acute myeloid leukemia in its current form is not optimal, and that the use of a more restricted definition of morphologic dysplasia results in more relevant risk stratification that is independent of other conventional prognostic factors.
authors.affiliation: Department of Pathology, Children's Hospital Boston, Boston, MA, USA.
authors.forename: Olga K
authors.initials: OK
authors.lastname: Weinberg
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Pozdnyakova
authors.affiliation: Department of Biostatistics and Computational Biology, Dana Farber Cancer Institute, Boston, MA, USA.
authors.forename: Federico
authors.initials: F
authors.lastname: Campigotto
authors.affiliation: Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: DeAngelo
authors.affiliation: Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Stone
authors.affiliation: Department of Biostatistics and Computational Biology, Dana Farber Cancer Institute, Boston, MA, USA.
authors.forename: Donna
authors.initials: D
authors.lastname: Neuberg
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Hasserjian
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D048430:Cell Shape; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000473:pathology*; D008297:Male; D008533:Megakaryocytes / Q000473:pathology*; D008875:Middle Aged; D022423:Myeloid Cells / Q000473:pathology*; D011379:Prognosis; D015203:Reproducibility of Results; D055815:Young Adult