Comparison of genetic and clinical aspects in patients with acute myeloid leukemia and myelodysplastic syndromes all with more than 50% of bone marrow erythropoietic cells

Abstract

Background: The World Health Organization separates acute erythroid leukemia (erythropoiesis in ≥50% of nucleated bone marrow cells; ≥20% myeloblasts of non-erythroid cells) from other entities with increased erythropoiesis - acute myeloid leukemia with myelodysplasia-related changes (≥20% myeloblasts of all nucleated cells) or myelodysplastic syndromes - and subdivides acute erythroid leukemia into erythroleukemia and pure erythroid leukemia subtypes. We aimed to investigate the biological/genetic justification for the different categories of myeloid malignancies with increased erythropoiesis (≥50% of bone marrow cells).

Design and methods: We investigated 212 patients (aged 18.5-88.4 years) with acute myeloid leukemia or myelodysplastic syndromes characterized by 50% or more erythropoiesis: 108 had acute myeloid leukemia (77 with acute erythroid leukemia, corresponding to erythroid/myeloid erythroleukemia, 7 with pure erythroid leukemia, 24 with acute myeloid leukemia with myelodysplasia-related changes) and 104 had myelodysplastic syndromes. Morphological and chromosome banding analyses were performed in all cases; subsets of cases were analyzed by polymerase chain reaction and immunophenotyping.

Results: Unfavorable karyotypes were more frequent in patients with acute myeloid leukemia than in those with myelodysplastic syndromes (42.6% versus 13.5%; P<0.0001), but their frequency did not differ significantly between patients with acute erythroid leukemia (39.0%), pure erythroid leukemia (57.1%), and acute myeloid leukemia with myelodysplasia-related changes (50.0%). The incidence of molecular mutations did not differ significantly between the different categories. The 2-year overall survival rate was better for patients with myelodysplastic syndromes than for those with acute myeloid leukemia (P<0.0001), without significant differences across the different acute leukemia subtypes. The 2-year overall survival rate was worse in patients with unfavorable karyotypes than in those with intermediate risk karyotypes (P<0.0001). In multivariate analysis, only myelodysplastic syndromes versus acute myeloid leukemia (P=0.021) and cytogenetic risk category (P=0.002) had statistically significant effects on overall survival.

Conclusions: The separation of acute myeloid leukemia and myelodysplastic syndromes with 50% or more erythropoietic cells has clinical relevance, but it might be worth discussing whether to replace the subclassifications of different subtypes of acute erythroid leukemia and acute myeloid leukemia with myelodysplasia-related changes by the single entity, acute myeloid leukemia with increased erythropoiesis ≥50%.

Figure 1.

Frequencies of aberrant and unfavorable karyotypes and the different molecular mutations in the MDS and AML cohorts and in the different AML subgroups (AEL, pEL, and AML-MRC) with ≥50% of bone marrow erythropoietic cells.

Figure 2.

Overall survival in the different hematologic entities with ≥50% of bone marrow erythropoietic cells comparing (A) the MDS (n=104) versus AML (n=108) cohort (P<0.0001), (B) early MDS subtypes (n=95) versus MDS-RAEB (n=23) (n.s.) and (C) the different AML subgroups (AEL, n=77; pure EL, n=7; AML-MRC, n=24; n.s.).

Figure 3.

Overall survival depending on the cytogenetic risk group (MRC revised criteria). Unfavorable karyotypes were associated with significantly inferior overall survival compared with intermediate karyotypes. (A) in all patients (n=212; P<0.0001), (B) in the MDS cohort (n=104; P<0.0001), and (C) in the AML cohort (n=108; P<0.0001).

Figure 4.

Overall survival depending on the cytogenetic risk group (MRC revised criteria). (A) When patients with intermediate risk (n=152) were considered, MDS patients (n=90) had better outcomes than those with AML (n=62; P=0.007); (B) in the unfavorable cytogenetic risk group (n=60), outcomes of patients with MDS (n=14) and AML (n=46) did not differ significantly.

Figure 5.

Overall survival depending on the history of disease, (A) in all patients (n=212). Patients with de novo disease had significantly better outcomes than patients with secondary disease (P=0.010), (B) in the MDS cohort (n=104; P=n.s.), and (C) in the AML cohort (n=108; n.s.).