Overall Survival in Acute Erythroleukemia According to Pathologic Features.

Acute erythroleukemia (AEL) is a rare subtype of acute myeloid leukemia (AML), comprising less than 5% of all AML, with a historically poor prognosis. According to the 2008 World Health Organization (WHO) classification, it is characterized by the presence of more than 50% erythroid precursors in the entire cellularity and more than 20% myeloblasts in the non-erythroid cell population. The clinical and pathologic features of this subtype have not been clearly defined, and due to the lack of sufficient clinical data, there are concerns that the current categorization might not truly reflect the differences among the cases and the distinction from myelodysplastic syndromes (MDS) and acute myeloid leukemia with myelodysplasia-related changes (AML-MRC). We reviewed ten years of AEL cases from the Moffitt Cancer Center (MCC), as well as high grade MDS and AML-MRC with erythroid predominance (>50% of marrow cells), and compared outcome of these cases according to disease subcategory.

Cases from the MCC data base from 2001 to 2011 were reviewed, identifying 77 cases with a bone marrow aspirate fulfilling the WHO criteria for AEL, and 23 cases of high grade MDS with erythroid predominance of more than 50% of cellularity. Pure erythroid leukemia cases were excluded. Upon further review, of the 77 AEL cases, 22 cases (28.5%) were de novo AEL, 27 cases (35%) evolved from antecedent MDS (MDS-AEL), and 28 cases (36.4%) were re-categorized into AML-MRC as shown by subsequent bone marrow biopsies. Pathological data of serial bone marrow biopsies and clinical data were collected. Patient survival was analyzed with Kaplan-Meier method from the date of diagnosis until death from any cause or last follow up visit. Survival curves were compared by the logrank test.

The median overall survival of 22 cases of de novo AEL is 25 months, while the median overall survival of 27 cases of MDS-AEL and 28 cases of AML-MRC are both 14 months. Patients with de novo AEL had better prognosis than those with AML-MRC (p=0.03). There were no significant statistical differences in overall survival between de novo AEL and MDS-AEL, or between MDS-AEL and AML-MRC (p=0.49 and 0.2, respectively).

The 23 cases of high grade MDS with erythroid predominance have a median survival of 51 months, compared to 26 months for all the analyzed cases of AML with myelodysplastic features, including MDS-AEL and AML-MRC, when the survival durations were calculated from the date of initial MDS diagnosis. When comparing this group of high grade MDS with MDS-AEL or AML-MRC, the differences were not statistically different (p=0.34).

We next analyzed survival of the AEL patients according to blast percentage. In this study, an arbitrary myeloblast count threshold of 10% of the overall marrow cellularity was used. Although myeloblast count did not significantly impact survival, when the cases were subcategorized based on the blast counts of serial bone marrow biopsies including those that did not meet the criteria for AEL, survival was significantly better in the patients with blast counts consistently lower than 10% of all bone marrow cellularity (p=0.03). In addition, patients with normal karyotype had significantly better survival than those with complex karyotypes (p=0.0017).

Our findings suggest that there are overlapping features among high grade MDS, AEL and AML-MRC. Serial bone marrow biopsies are more critical in establishing a diagnosis and predicting prognosis than blast percentage calculations on a single marrow. Indicators such as complex cytogenetic changes and appropriate blast percentage threshold are necessary to further refine the classification.

No relevant conflicts of interest to declare.