Background: Secondary acute myeloid leukemia (sAML) is associated with shorter survival compared to de novo AML and remains an ongoing challenge in hematooncology. The pathogenetic spectrum of sAML is heterogeneous and until now accounts for 15-30% of overall AML cases. Among sAML, therapy-related AML (tAML) arises from prior cytotoxic, radiation, or immunosuppressive therapy, while MDS/MPN-AML develops from the previous clonal disorder of hematopoiesis. However, the independent prognostic value of sAML itself has been questioned, as the diagnosis is often connected with older age, severe comorbidities, and an unfavorable cytogenetic and molecular profile.
Aims: In the study, we aimed to characterize MDS/MPN-AML and tAML patients treated at our center and evaluate relevant prognostic factors for survival as well as treatment outcomes in these subtypes of AML.
Methods: We performed the single-center retrospective analysis of MDS/MPN-AML and tAML patients diagnosed between 2013 and 2018 in the Hematology Department in Lodz, Poland. Simultaneously, the demographic data, clinical factors, and laboratory findings were collected. For statistical analysis, we used Cox proportional hazard models, the Kaplan-Meier method, and log-rank as well as Chi2 tests.
Results: The study included 110 patients with either MDS/MPN-AML (n=78) and tAML (n=32), with a median age of 66 (range 31-86). The median follow-up was 3.2 months (95%CI: 2.5-5.3). The most common hematological disorder preceding sAML was MDS (n=48), while the most frequent neoplasm previous to tAML was breast cancer (n=9). The median overall survival (OS) for MDS/MPN-AML patients was 4.1 months (95%CI: 2.5-7.0) and for tAML 2.8 months (95%CI: 1.6-5.6). In patients treated intensively, the median OS was 13.9 months (95%CI: 7.9-24.5), and in patients treated non-intensively it was 2.5 months (95%CI: 1.6-3.0) (3.3, 2.9, 1.0 months for LD-AraC, azacitidine, and best supportive care/hydroxyurea, respectively) (p<0.0001) (Figure 1.). In the multivariate Cox regression model for OS the factors like age at diagnosis (HR 1.03, 95%CI: 1.00-1.06), higher ECOG score (interpreted as 2/3/4 vs. 0/1) (HR 1.85, 95%CI: 1.08-3.15), hypoalbuminemia (HR 3.20, 95%CI: 1.95-5.24), and percentage of bone marrow blasts infiltration (HR 1.01, 95%CI: 1.00-1.03) were independent predictors of poor survival for the whole cohort. On the other hand, the intensive treatment approach was related to longer survival (HR 0.42, 95%CI: 0.21-0.82) in both groups considered together. There were no differences in OS between MDS/MPN-AML and tAML (p=0.86), as well as within particular groups: MDS-AML vs. MPN-AML (p=0.21) and comparing each tAML subgroup separately (p=0.19). The importance of alloHSCT in improving survival can be emphasized, although few patients (n=8) were eligible for the procedure and no effect was shown on significantly prolonging OS, considering the intensively treated (p=0.14).
Summary/Conclusion: The poor outcomes of sAML treatment are compounded by factors such as low response rates, high early mortality and baseline general condition of the patient. Both the MDS/MPN-AML and tAML groups showed similar clinical characteristics, a high percentage of unfavorable cytogenetic profiles, and there were no significant differences in OS. Clinical and laboratory variables, like age, ECOG score, blasts level infiltration, and albumin level have proven to be independent prognostic factors of OS in sAML patients. The positive influence of intensive chemotherapy might be highlighted, nevertheless, optimizing treatment for that high-risk subpopulation remains a crucial issue.
Figure 1.
Keywords: Survival, Acute myeloid leukemia, Therapy-related AML, Secondary