Prognostic significance of dysplastic features of hematopoiesis in patients with de novo acute myelogenous leukemia

Abstract

The detection of dysplastic features of hematopoiesis in de novo acute myeloid leukemia (AML) by light microscopy is defined as AML with trilineage myelodysplasia (AML/TLMD). The prognostic relevance of these dysplastic features for patients with de novo AML remains unclear. In order to evaluate the role of dysplasia in de novo AML, bone marrow aspirates from 69 patients were analyzed prospectively and investigated separately for erythropoiesis, granulopoiesis and megakaryopoiesis by three independent investigators. The overall complete remission (CR) rate was 48.8% and partial remission (PR) or nonresponders constituted 52.2% of the patients investigated. The median overall survival time was 5 months with a disease-free interval of 3.5 months for all patients. Dysgranulopoiesis (DysG) was observed in 30.4%, dysmegakaryopoiesis (DysM) in 50.7%, and dyserythropoiesis (DysE) in 43.5%. Of all patients, 26.0% showed trilineage dysplastic features and were thus classified as AML/TLMD. A significantly worse prognosis (Kaplan-Meyer plot, Student's t-test) was calculated for those patients with detection of only DysG (p = 0.002), DysM (p = 0.02), DysE (p = 0.04) as compared with patients without any dysplastic signs. An unfavorable karyotype was correlated with patients showing DysG (P = 0.02) and DysM (P = 0.04). For these patients with an unfavorable karyotype, the occurrence of any dysplastic features had no additional prognostic impact. Dysplastic features (DysG, DysM, DysE) seem to be an important prognostic factor in de novo AML correlating with short overall survival. DysG and DysM correlated well with the appearance of unfavorable chromosomal abnormalities. It may be reasonable to assume that patients with dysplastic features should be considered for more aggressive treatment schedules at the time of diagnosis.

Characteristics of acute myeloid leukemia with myelodysplasia‐related changes: A retrospective analysis in a cohort of Chinese patients

“…It still remains controversial whether OS and DFS will be affected by MLD. We can found some other reports [6,[9][10][11][12][13][14][15] supporting that MLD affected the prognosis of AML patients. However, if looking carefully into their results, they did not show that MLD was an independent prognostic factor in patient with AML.…”

Low expression of the myeloid differentiation antigen CD65s, a feature of poorly differentiated AML in older adults: study of 711 patients enrolled in ECOG trials

“…24 Head 25 developed a classification of AML by dividing into true de novo AML and AML related to myelodysplasia (MDS-related AML), in which the majority of AML in older adults was included in the MDS-related group. The rationale of his model, among other considerations, was based on common cytogenetic abnormalities shared by MDS and older AML, in particular, aberrations of chromosomes 5 and 7, an observation made earlier by Rowley et al 26 Trilineage dysplasia may 27,28 or may not 29 be more frequent in older AML and causally related to the poorer outcome in this patient population. More recent studies have suggested that the resistance experienced in older adult and MDS-related or secondary AML may, at least in part, derive from the presence of functionally active multidrug-resistance Pglycoprotein 30 or diminished apoptotic responses when exposed to ara-c or daunomycin.…”

MLD according to the WHO classification in AML has no correlation with age and no independent prognostic relevance as analyzed in 1766 patients

“…A detailed description of the study has been published previously. 31 In patients up to 60 years, first induction therapy consisted of triple therapy with 10 mg/m 2 mitoxantrone (days 4-8), 100 mg/m 2 cytosine arabinoside (ara-C) (days 1-8), and 100 mg/m 2 VP16 (days [4][5][6][7][8]. Second induction consisted of 100 mg/m 2 amsacrine (m-AMSA-days 1-5) and 2 ϫ 1000 mg/m 2 araC every 12 hours days 1 to 5 (MAMAC [m-AMSA and median dose ara-C]).…”

“…[1][2][3][4][5] For more than 30 years the clinical significance of morphological dysplastic (dys) features of hematopoietic cell lineages in AML has been examined with different and contradictory results. [6][7][8][9][10][11][12][13][15][16][17] Most studies have been performed in de novo AML.…”