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Morphologic Dysplasia in De Novo Acute Myeloid Leukemia (AML) Is Related to Unfavorable Cytogenetics but Has No Independent Prognostic Relevance Under the Conditions of Intensive Induction Therapy: Results of a Multiparameter Analysis From the German AML Cooperative Group Studies

Torsten Haferlach, Claudia Schoch, Helmut Löffler, Winfried Gassmann, Wolfgang Kern, Susanne Schnittger, Christa Fonatsch, Wolf-Dieter Ludwig, Christian Wuchter, Brigitte Schlegelberger, Peter Staib, Albrecht Reichle, Uschi Kubica, Hartmut Eimermacher, Leopold Balleisen, Andreas Grüneisen, Detlef Haase, Carlo Aul, Jochen Karow, Eva Lengfelder, Bernhard Wörmann, Achim Heinecke, Maria Cristina Sauerland, Thomas Büchner, Wolfgang Hiddemann

From the Department of Medicine III, Ludwig-Maximilians-University, Grosshadern, Munich, Germany.

Address reprint requests to Torsten Haferlach, MD, Department of Internal Medicine III, Laboratory for Leukemia Diagnostics, Ludwig-Maximilians-University, Marchioninistr 15, 81377 Munich; email: torsten.haferlach{at}med3.med.uni-muenchen.de.

Purpose: On the basis of cytomorphology according to the French-American-British (FAB) classification, we evaluated the prognostic impact of dysplastic features and other parameters in de novo acute myeloid leukemia (AML). We also assessed the clinical significance of the recently introduced World Health Organization (WHO) classification for AML, which proposed dysplasia as a new parameter for classification.

Patients and Methods: We analyzed prospectively 614 patients with de novo AML, all of whom were diagnosed by central morphologic analysis and treated within the German AML Cooperative Group (AMLCG)-92 or the AMLCG-acute promyalocytic leukemia study.

Results: Patients with AML M3, M3v, or M4eo demonstrated a better outcome compared with all other FAB subtypes (P < .001); no prognostic difference was observed among other FAB subtypes. The presence or absence of dysplasia failed to demonstrate prognostic relevance. Other prognostic markers, such as age, cytogenetics, presence of Auer rods, and lactate dehydrogenase (LDH) level at diagnosis, all showed significant impact on overall and event-free survival in univariate analyses (P < .001 for all parameters tested). However, in a multivariate analysis, only cytogenetics (unfavorable or favorable), age, and high LDH maintained their prognostic impact. Dysplasia was not found to be an independent prognostic parameter, but the detection of trilineage dysplasia correlated with unfavorable cytogenetics.

Conclusion: Our results indicate that cytomorphology and classification according to FAB criteria are still necessary for the diagnosis of AML but have no relevance for prognosis in addition to cytogenetics. Our results suggest that the WHO classification should be further developed by using cytogenetics as the main determinant of biology. Dysplastic features, in particular, have no additional impact on predicting prognosis when cytogenetics are taken into account.

Supported by grant no. M17/92/Bü1 from Deutsche Krebshilfe, Bonn, Germany.

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