Prognosis of Acute Myeloid Leukemia with Myelodysplasia-Related Changes According to the Different Subgroups of the WHO 2016 Classification in Patients Candidates to Intensive Chemotherapy

Introduction: In the WHO 2016 classification, within the category of Acute Myeloid Leukemia with Myelodysplasia-Related Changes (AML-MRC), 3 subgroups are distinguished: 1) AML with Defining Cytogenetic Abnormality (AML-DCA) 2) AML with Previous History of MDS or MDS/MPN (AML-PHM) and 3) AML with Multilineage Dysplasia (AML-MD). The prognostic impact of significant Multilineage Dysplasia in patients without accompanying adverse cytogenetics or a history of prior hematologic malignancy is currently unclear.

Objectives: To analyze the impact of MD as a classification criterion of AML-MRC compared to the rest of AML-MRC subgroups in terms of survival. To analyze if there are characteristics in global cohort that could us to predict worse survival outcomes.

Material and methods: We performed a retrospective analysis of 48 patients candidates to intensive chemotherapy treated in a single center between 2013 and 2019. We divided our cohort into 2 groups 1) AML-MD and 2) AML-DCA + AML -PHM. The baseline characteristics of each group were compared using the Chi² test. The survival analysis was performed through Kaplan-Meier method and the risk was calculated with Cox regression. The Overall Survival (OS) was defined as the time from diagnosis to death and the Event-Free Survival (EFS) as the time from diagnosis to either relapse or death. P<0.05 was defined as statistically significant difference.

Results: The baseline characteristics of the global cohort are reflected in Table 1. The median follow-up of the entire population was 15 months (0-77). The median OS and EFS were 18 months and 11 months, respectively. The median OS was 14 months in group 1 vs 19 months in group 2 with a Hazard Ratio (HR) of 0.9 (95% CI 0.3-2.2, p = 0.8). The median EFS in Group 1 was 10 months vs 14 months in group 2 (HR 0.9 95% CI (0.4-2.1), p = 0.9) (Image 1). In global cohort, 11 patients had a complex karyotype at diagnosis. The median OS in these patients was 23 vs 16 months in those with other cytogenetic alterations or normal karyotype (HR 0.8 (95% CI (0.3-2.1), p = 0.8) and EFS 14 vs 10 months [HR 1.1 ( 95% CI (0.5-2.5), p = 0.6]. 34 patients received transplantation (HSCT) as consolidation therapy (33 allogeneic, 1 autologous). In transplanted patients the median OS was 26 months vs 4 months in those that did not consolidate with transplant [HR 4.5 (95% CI 2-10, p <0.0001] and the EFS 14 months vs 3 months [HR = 4.2, 95% CI (2-8.5), p = <0.001] (Image 2). We performed a multivariate analysis including AML-DM vs AML-DCA + AML -PHM, complex karyotype, European LeukemiaNet classification at diagnosis, response to induction and consolidation with transplantation vs not received transplantation. The variables with a significant HR for EFS were not received transplantation as consolidation therapy [HR 2.8, 95% CI (1.2-6.1), p = 0.01] and the response to induction [HR 1.6, 95% CI (1.05-2.4), p = 0.3]. The only variable with a significant HR for OS was consolidation with transplantation (HR 3.3 (CI 95 % 1.4-8), p <0.01).

Conclusions: patients with AML-MRC are a high-risk group in terms of OS and EFS. Although allogeneic transplantation in these patients improves survival, the prognosis remains poor. In our cohort, morphological dysplasia without cytogenetic criteria or previous hematological neoplasia identified a high-risk subgroup with similar results to the other two subgroups. The results in the AML-MD subgroup are currently controversial, so we probably need to better characterize this subgroup in future studies.