Different Cytogenetic Patterns in Specified Categories of Secondary AML: Results of a Population-Based Registry Study,
Authors: Norgaard Jan M. , Oestgaard Lene S.G. , Andersen Mette K. , Kallenbach Maria , Johansen Preben , Bendix Knud , Kerndrup Gitte , Preiss Birgitte , Dufva Inge , Timshel Susanne , Kristensen Joergen , Brown Peter de Nully 
Published: October 2019

Abstract
Abstract 3586
The prognosis of leukemia patients suffering from secondary AML (sAML) compared to that of patients with de novo AML is dismal. The group of sAMLs is heterogeneous and includes AML arising from an antecedent myelodysplastic (MDS) or myeloproliferative neoplasm (MPN), and AML caused by cytotoxic therapy (tAML). In the present retrospective population- and national registry-based analysis we identified 612 (27%) patients as having some form of sAML. Cytogenetic risk group patterns and clinical outcomes among the different categories of sAML were compared to those of 1635 de novo AML cases identified in a total population of 2261 patients (data missing in 14 cases). The cohort represents >90% of all AML patients diagnosed and treated in Denmark during the eleven-year period January 2000 through December 2010.
The following groups of sAMLs were identified: A. Patients with an antecedent MDS or chronic myelomonocytic leukemia (324 cases), B. Patients with antecedent MPN (excluding chronic myeloid leukemia, 108 cases), C. Patients previously treated with chemo- and/or radiotherapy for another hematological neoplasm (113 cases), and D. Patients previously treated with chemo- and/or radiotherapy for another non-hematological neoplasm or disease (67 cases). For all 1168 curatively treated patients in the total cohort, presenting cytogenetic abnormalities (categorized according to revised MRC-criteria, D. Grimwade et al. Blood, 2010), age, leukocyte count, and type of leukemia (secondary vs. de novo) were all prognostic parameters found to be highly statistically significant to probability of attainment of complete remission (CR) and to overall survival (OS) in univariate as well as multivariate analyses, data not shown. There were strikingly fewer patients showing favorable cytogenetic abnormalities among sAMLs. Focusing on the above defined 4 categories of sAML, patterns of cytogenetic risk group distribution were strikingly and statistically significantly different (nevaluable= 418, p-value, Chi-square <10−4), Table 1, with favorable cytogenetic abnormalities being relatively more frequent in sAML-category D.Table 1.Category of sAML and cytogenetic abnormalitiesCategory of sAMLCytogenetics, (revised MRC-categories)A (MDS and CMML) (%)B (MPN) (%)C (Cytotoxic therapy, hematological neoplasm) (%)D (Cytotoxic therapy, non-hematological neoplasm a.o.) (%)TotalFavorable1 (0.5)1 (1.3)2 (2.9)10 (18.5)14Intermediate157 (72)52 (68.4)49 (70)29 (53.7)287Unfavorable60 (27.5)23 (30.3)19 (27.1)15 (27.8)117Total218767054418
Additionally, in the sAMLs we found age, cytogenetic abnormalities, and white blood cell count (WBC) to be highly statistically significant to probability of attainment of CR and to duration of OS. By contrast, we did not find the specific sAML category to be of significance to probability of attainment of CR or to duration of OS, Table 2, Fig. 1.Table 2.Factors of significance to probability of attainment of CR and to OS in 246 cases of secondary AMLProbability of CR (Logistic regression, nevaluable= 246)Probability of overall survival (Cox regression, nevaluable= 246)VariableOdds ratio (OR)95% CI of ORP valueHazard ratio95% CI of HRP valueAge1.071.03–1.11<10-41.021.01–1.040.006Cytogenetics3.291.71–6.34<10-42.021.46–2.78<10-4Male gender--NS--NSWBC1.011.003–1.0170.0061.0041.002–1.0070.001sAML-category--NS--NS
In conclusion, from these analyses we confirm the prognostic significance of presence of sAML as well as other well established prognostic parameters in AML. We find cases of sAML-category D, i.e., patients previously treated with chemo- and/or radiotherapy for another non-hematological neoplasm or disease, to exhibit favorable cytogenetic abnormalities relatively frequently. Probability of attainment of CR and OS duration were similar in the four different specific categories of sAML. Well established prognostic parameters including age, cytogenetic abnormalities, and WBC are of significant prognostic value in sAML.

Disclosures:
No relevant conflicts of interest to declare.