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Pretherapeutic Identification of High Risk AML Patients

G.Valet1), R.Repp2)

1) Max-Planck-Institut für Biochemie, Martinsried
2) Medizinische Klinik III der Universität Erlangen, Germany

1. Background: AML patients are frequently stratified by prognostic parameters into therapeutic subgroups (L2). Stratification helps therapy susceptible patients but is of no use to non responders. There is significant clinical interest to identify non responder patients pretherapeutically for individualised therapy adaptation or switch to alternative therapies.

2. Goal: Classification of the SHG-96 multicenter AML trial database (L2) to identify high risk AML-patients prior to therapy (L1).

3. Results: The algorithmic (non parametric) classification of the available immunophenotype, cytogenetic and clinical parameters (fig.1) shows that predictive values of 100% for 5-year nonsurvival and of 88.6% for 2-year nonsurvival (fig.2) are obtained.
The discriminatory data patterns (disease classification masks) contain 7 parameters for the 5-year classification and 12 parameters for the 2-year classifications (fig.3) . Patient age and %CD4, %CD45 positive AML blasts are equally selected in both classifications. The other parameters of the disease classification masks are different.
The reclassification of the learning set shows that correct classification is obtained in most instances with mask coincidence factors between 0.57-1.00. This indicates that already a partial fit of the patient classification masks with the two disease classification masks >5-year survivors and 5-year nonsurvivors is sufficient for correct classifications (fig.4). The differences between the predictive (fig.5) and the prognostic (fig.6) disease classification masks illustrate that individualised and group oriented predictions refer to quite different parameter patterns.

4. Conclusion and Outlook: Immunophenotype parameter patterns identify high risk patients with high predictive values. Cytogenetic parameters were not selected, probably because they occur in only about half of the patients as opposed to the CD antigen expression on all cells.
It seems promising to perform multiparametric CD measurements which include the CD antigens of the disease classification masks identified in this study. In addition the degree of antigen expression, antigen ratios and scatter of antigen distributions have then to be evaulated in addition to cell frequency to further increase the predictive values to >95% for the purpose of individualized pretherapeutic risk assessment.

Literature References:
L1. Valet G, Repp R, Link H, Ehninger G, Gramatzki M and SHG-AML study group. Pretherapeutic identification of high risk acute myeloid leukemia (AML) patients from immunophenotype, cytogenetic and clinical parameters. Cytometry 53B:4-10, (2003) *external link (PDF)
L2. Repp R, Schaekel U, Helm G, Thiede C, Soucek S, Pascheberg U, Wandt H, Aulitzky W, Bodenstein H, Kuse R, Link H, Ehninger G, Gramatzki M and AML-SHG Study Ehninger G, Gramatzki M and SHG-AML study group. Immunophenotyping is an independent factor for risk stratification in AML. Cytometry 53B:11-19, (2003) *external link (PDF)

© 2017 G.Valet
Last Update: Jan 01,2016