This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Haferlach, T. Articles by Hiddemann, W. Search for Related Content PubMed PubMed Citation Articles by Haferlach, T. Articles by Hiddemann, W. Social Bookmarking                            What's this?

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.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				M. Podberezin, R. Angeles, D. Peace, D. Rondelli, J. Quigley, V. Lindgren, and S. Gaitonde Acute Myeloid Leukemia With Myelodysplasia-Related Changes: A New Entity Defined by the WHO 2008 Classification of Hematopoietic and Lymphoid Neoplasms Lab Med, July 1, 2009; 40(7): 397 - 400. [Abstract] [Full Text] [PDF]

				F. Schneider, E. Hoster, M. Unterhalt, S. Schneider, A. Dufour, T. Benthaus, G. Mellert, E. Zellmeier, S. K. Bohlander, M. Feuring-Buske, et al. NPM1 but not FLT3-ITD mutations predict early blast cell clearance and CR rate in patients with normal karyotype AML (NK-AML) or high-risk myelodysplastic syndrome (MDS) Blood, May 21, 2009; 113(21): 5250 - 5253. [Abstract] [Full Text] [PDF]

				O. K. Weinberg, M. Seetharam, L. Ren, K. Seo, L. Ma, J. D. Merker, J. Gotlib, J. L. Zehnder, and D. A. Arber Clinical characterization of acute myeloid leukemia with myelodysplasia-related changes as defined by the 2008 WHO classification system Blood, February 26, 2009; 113(9): 1906 - 1908. [Abstract] [Full Text] [PDF]

				T. Buchner, W. E. Berdel, C. Haferlach, T. Haferlach, S. Schnittger, C. Muller-Tidow, J. Braess, K. Spiekermann, J. Kienast, P. Staib, et al. Age-Related Risk Profile and Chemotherapy Dose Response in Acute Myeloid Leukemia: A Study by the German Acute Myeloid Leukemia Cooperative Group J. Clin. Oncol., January 1, 2009; 27(1): 61 - 69. [Abstract] [Full Text] [PDF]

				A. Kohlmann, E. Haschke-Becher, B. Wimmer, A. Huber-Wechselberger, S. Meyer-Monard, H. Huxol, U. Siegler, M. Rossier, T. Matthes, M. Rebsamen, et al. Intraplatform Reproducibility and Technical Precision of Gene Expression Profiling in 4 Laboratories Investigating 160 Leukemia Samples: The DACH Study Clin. Chem., October 1, 2008; 54(10): 1705 - 1715. [Abstract] [Full Text] [PDF]

				U. Bacher, C. Haferlach, W. Kern, T. Haferlach, and S. Schnittger Prognostic relevance of FLT3-TKD mutations in AML: the combination matters--an analysis of 3082 patients Blood, March 1, 2008; 111(5): 2527 - 2537. [Abstract] [Full Text] [PDF]

				H. Wandt, U. Schakel, F. Kroschinsky, G. Prange-Krex, B. Mohr, C. Thiede, U. Pascheberg, S. Soucek, M. Schaich, and G. Ehninger MLD according to the WHO classification in AML has no correlation with age and no independent prognostic relevance as analyzed in 1766 patients Blood, February 15, 2008; 111(4): 1855 - 1861. [Abstract] [Full Text] [PDF]

				T. Buchner, W. E. Berdel, C. Schoch, T. Haferlach, H. L. Serve, J. Kienast, S. Schnittger, W. Kern, J. Tchinda, A. Reichle, et al. Double Induction Containing Either Two Courses or One Course of High-Dose Cytarabine Plus Mitoxantrone and Postremission Therapy by Either Autologous Stem-Cell Transplantation or by Prolonged Maintenance for Acute Myeloid Leukemia J. Clin. Oncol., June 1, 2006; 24(16): 2480 - 2489. [Abstract] [Full Text] [PDF]

				E. J. Jabbour, E. Estey, and H. M. Kantarjian Adult Acute Myeloid Leukemia Mayo Clin. Proc., February 1, 2006; 81(2): 247 - 260. [Abstract] [Full Text] [PDF]

				A. van Rhenen, N. Feller, A. Kelder, A. H. Westra, E. Rombouts, S. Zweegman, M. A. van der Pol, Q. Waisfisz, G. J. Ossenkoppele, and G. J. Schuurhuis High Stem Cell Frequency in Acute Myeloid Leukemia at Diagnosis Predicts High Minimal Residual Disease and Poor Survival Clin. Cancer Res., September 15, 2005; 11(18): 6520 - 6527. [Abstract] [Full Text] [PDF]

				T. Haferlach, A. Kohlmann, S. Schnittger, M. Dugas, W. Hiddemann, W. Kern, and C. Schoch Global approach to the diagnosis of leukemia using gene expression profiling Blood, August 15, 2005; 106(4): 1189 - 1198. [Abstract] [Full Text] [PDF]

				W. Kern, D. Voskova, C. Schoch, W. Hiddemann, S. Schnittger, and T. Haferlach Determination of relapse risk based on assessment of minimal residual disease during complete remission by multiparameter flow cytometry in unselected patients with acute myeloid leukemia Blood, November 15, 2004; 104(10): 3078 - 3085. [Abstract] [Full Text] [PDF]

				T. Buchner, W. Hiddemann, W. E. Berdel, B. Wormann, C. Schoch, C. Fonatsch, H. Loffler, T. Haferlach, W.-D. Ludwig, G. Maschmeyer, et al. 6-Thioguanine, Cytarabine, and Daunorubicin (TAD) and High-Dose Cytarabine and Mitoxantrone (HAM) for Induction, TAD for Consolidation, and Either Prolonged Maintenance by Reduced Monthly TAD or TAD-HAM-TAD and One Course of Intensive Consolidation by Sequential HAM in Adult Patients at All Ages With De Novo Acute Myeloid Leukemia (AML): A Randomized Trial of the German AML Cooperative Group J. Clin. Oncol., December 15, 2003; 21(24): 4496 - 4504. [Abstract] [Full Text] [PDF]

				S. Schnittger, M. Weisser, C. Schoch, W. Hiddemann, T. Haferlach, and W. Kern New score predicting for prognosis in PML-RARA+, AML1-ETO+, or CBFBMYH11+ acute myeloid leukemia based on quantification of fusion transcripts Blood, October 15, 2003; 102(8): 2746 - 2755. [Abstract] [Full Text] [PDF]

				J. M. Bennett Morphologic Dysplasia in Acute Myeloid Leukemia: Importance of Granulocytic Dysplasia J. Clin. Oncol., August 1, 2003; 21(15): 3004 - 3004. [Full Text] [PDF]

				T. Haferlach, W. Kern, C. Schoch, W. Hiddemann, and M. C. Sauerland In Reply: J. Clin. Oncol., August 1, 2003; 21(15): 3004 - 3005. [Full Text] [PDF]