Acute erythroid leukemia as defined in the World Health Organization classification is a rare and pathogenetically heterogeneous disease

Abstract

The diagnostic criteria for acute erythroid leukemia have been controversial since this disease was initially described. Using the current World Health Organization classification criteria, we retrospectively reviewed cases of acute myeloid leukemia or myelodysplastic syndrome in which erythroid precursors were ≥50% of the bone marrow nucleated cell population and the diagnosis of erythroleukemia was considered using older classification schemes. We collected 90 cases and separated them into four diagnostic groups: acute erythroid leukemia, erythroleukemia or erythroid/myeloid type (n=20); acute myeloid leukemia with myelodysplasia-related changes (n=22); therapy-related acute myeloid leukemia (n=32); and refractory anemia with excess blasts and preceding or concurrent history of erythropoietin therapy for anemia (n=16). Patients with acute erythroid leukemia were the youngest patient group and had the best overall survival. There was a statistically significant difference in overall survival between patients with acute erythroid leukemia versus acute myeloid leukemia with myelodysplasia-related changes (P=0.003) and between patients with acute erythroid leukemia versus therapy-related acute myeloid leukemia (P<0.0001). The presence of complex cytogenetic abnormalities (>3) was the only statistically significant independent variable that adversely affected survival in the acute erythroid leukemia group. Monosomy 5/del(5q) and monosomy 7/del(7q) were overrepresented in the context of complex chromosomal abnormalities. Our data suggest that acute erythroid leukemia, as currently defined in the World Health Organization classification, has become a rare disease. Most cases reported previously as erythroleukemia are now classified as other entities. In addition, our data suggest that the current definition of acute erythroid leukemia, erythroleukemia type remains heterogeneous. One subset of acute erythroid leukemia patients has relatively low blast counts and are diploid. The prognosis of this patient subset is relatively good. The other subset has cytogenetic abnormalities similar to those in myelodysplastic syndromes and a poor prognosis.

Acute erythroid leukemia with <20% bone marrow blasts is clinically and biologically similar to myelodysplastic syndrome with excess blasts

“…Both acute erythroleukemia and refractory anemia with excess blasts and erythroid predominance (MDS-erythroid) demonstrated more frequent very-poor-risk cytogenetic abnormalities (including significantly more frequent -7/del7q in MDS-erythroid) compared to MDS-typical, which further confirms recent findings that erythroid-rich refractory anemia with excess blasts and acute erythroleukemia have a similar prognosis regardless of blast count and that karyotype risk assessment provides better prognostic stratification than blast count across the spectrum of erythroid-rich myeloid neoplasms. 4,8,17 The underlying biology of the marked erythroid proliferations in erythroid-rich refractory anemia with excess blasts and acute erythroleukemia is not well understood. As shown previously, it is not likely due to exogenous erythropoiesis stimulating agent administration 20 or endogenous erythropoietin production.…”

“…As described in previous acute erythroleukemia studies, morphologic dysplasia is nearly ubiquitous in the erythroid lineage, ring sideroblasts are common, and dysplasia is also seen in megakaryocytes and granulocytes. 8,[16][17][18] The mutational profile of acute erythroleukemia, with common TP53 mutation (33%) and uncommon FLT3 (3%) and NPM1 (5%) mutations, is different from most other acute myeloid leukemia subtypes, 9,10,19 but similar to the distribution of these mutations in refractory anemia with excess blasts. The common cytogenetic abnormalities observed in acute erythroleukemia, such as -5/5q-and -7/7q-, are also frequent in de novo refractory anemia with excess blasts.…”

“…Recent studies have suggested that acute erythroleukemia may be closer to myelodysplastic syndrome than to other subtypes of acute myeloid leukemia in terms of its genetic characteristics and clinical behavior. [8][9][10] However, many prior acute erythroleukemia series have included therapy-related myeloid neoplasms or cases known to have progressed from pre-existing myelodysplastic syndromes, which often show different molecular genetic characteristics and prognosis from their de novo counterparts. Until now, the features of de novo acute erythroleukemia have not been directly compared with de novo myelodysplastic syndrome with a similar absolute bone marrow blast percentage.…”

Acute myeloid leukemia with expanded erythropoiesis

“…[4][5][6] The common findings were high incidence of unfavorable karyotypes, low frequency of NPM1, FLT3 and RAS mutations, and poor prognosis. 4,[6][7][8][9][10] In this issue of Haematologica, Bacher et al 4 have compared some genetic and clinical aspects of AML and MDS with expanded erythropoiesis. On the basis of the observed better 2-year overall survival rate of MDS patients (n=104) in comparison to those classified as having AML (combined cohort of 77 AEL and 24 AML-MRC), the authors propose continuing separating MDS with expanded erythropoiesis from AML.…”

“…5 The same authors also separately described a group of 18 patients with primary erythroid leukemia in which complex karyotypes were noted in all 16 patients with available cytogenetic data. 14 Kasyan et al 8 reviewed a cohort of 90 patients with hematologic malignancies with expanded erythropoiesis, dividing them according to the WHO 2008 classification. Although the separate groups of patients were rather small, this study confirmed the negative prognostic significance of complex karyotypes within the AEL group and the negative prognostic significance of therapy-related AEL, independently of cytogenetics.…”