The recent review article by Vardiman et al on the World Health Organization (WHO) classification of myeloid neoplasms1described the diagnostic criteria for acute erythroleukemia. Of particular interest to us is the description of acute erythroid/myeloid leukemia. According to the WHO,2 acute erythroid/myeloid leukemia is defined as having at least 50% erythroid precursors in the entire marrow nucleated cell population and myeloblasts that account for at least 20% of the nonerythroid cell (NEC) population.

We recently have seen in our hospital/consultation service 5 patients (Table1) with bone marrow aspirates revealing 4%-11.6% myeloblasts and erythroid precursors comprising 58.2%-83.6% of the nucleated cells within the marrow, based on a 500-cell differential count. The percentage of myeloblasts among the nonerythroid cells ranged from 22.6% to 28.4%. None contained more than 30% pronormoblasts, a finding that previously has been shown to be a negative prognostic indicator.3,4 None contained sufficient dysplasia to be classified as acute leukemia with multilineage dysplasia, a diagnosis that requires dysplasia in at least 50% of the cells of at least 2 lineages.2 In addition, the one case with more than 80% erythroid precursors revealed erythroid maturation and did not meet the criteria for pure erythroid leukemia.2 All 5 cases were diagnosed as acute erythroleukemia.

Table 1.

Cell differential, cytogenetic results, and outcomes for patients with acute erythroleukemia

Patient no.Age, sexBlasts, % of totalErythroid precursors, %Blasts, % of NECCytogeneticsOutcome
61, M 4.0 83.6 24.0 Abnormal* Alive 3 months after diagnosis, no therapy  
44, M 7.0 75.4 28.4 Normal male Relapsed 
60, M 7.4 67.2 22.6 Abnormal Died of disease 2 months after diagnosis, standard chemotherapy  
23, M 11.6 58.2 27.0 Normal male Clinical remission, S/P ALLO-BMT 
81, F 7.0 75.0 28.0 Normal female Lost to follow-up 
Patient no.Age, sexBlasts, % of totalErythroid precursors, %Blasts, % of NECCytogeneticsOutcome
61, M 4.0 83.6 24.0 Abnormal* Alive 3 months after diagnosis, no therapy  
44, M 7.0 75.4 28.4 Normal male Relapsed 
60, M 7.4 67.2 22.6 Abnormal Died of disease 2 months after diagnosis, standard chemotherapy  
23, M 11.6 58.2 27.0 Normal male Clinical remission, S/P ALLO-BMT 
81, F 7.0 75.0 28.0 Normal female Lost to follow-up 

M indicates male; and F, female.

*

Abnormal karyotype included 45-46, XY, −5, −7, add (8)(p21)[2], −15[1], add(17)(p11.2), −21[1], +mar [13].

Abnormal karyotype included 41-45, X, −Y, del(5)(q13q33), −16, add(21)(q22), dic(17;20)(p13;q11.2)+20, add(20)(q11.2).

Status after allogeneic bone marrow transplantation.

The transition from the French-American-British (FAB) classification of myeloid neoplasms to the WHO classification included a reduction from 30% to 20% in the required blast percentage within the marrow for a diagnosis of acute leukemia, based upon cohort data indicating similar therapeutic responses and outcomes using these 2 thresholds. To our knowledge, there are no analogous data specifically supporting the changes made to diagnostic criteria for acute erythroleukemia. The difference between 30% and 20% myeloblasts as a percentage of NECs in an erythroid-predominant myeloid neoplasm may not represent a true biologic difference but will certainly be used by clinicians making treatment decisions.

When the 20% blast percentage cut-off is incorporated into the criteria for erythroleukemia described above, the diagnosis of acute leukemia can be rendered with a relatively low myeloblast percentage. In our cases, the most extreme example was 4% myeloblasts within the bone marrow. In addition, the prevalence of erythroid hyperplasia within cases of myelodysplasia5,6 may make this scenario more commonplace than is currently recognized, since erythroid-predominant cases will require at most 10% total myeloblasts to fulfill criteria for acute erythroleukemia. A patient with 49% erythroid precursors and 10% myeloblasts would be diagnosed as having refractory anemia with excess blasts, type 2 (RAEB-2); the same patient easily could be diagnosed with acute erythroleukemia if the erythroid precursor percentage were determined to be 51% with the same myeloblast percentage. In some cases, other causes of erythroid hyperplasia with slightly elevated blast counts also could be diagnosed incorrectly as acute erythroleukemia.

In the absence of data supporting the changes included in the WHO classification, we should critically assess the appropriateness of assigning acute leukemia diagnoses to patients with fewer than 10% (and in one of our cases, fewer than 5%) myeloblasts. These cases of acute erythroleukemia with a low percentage of myeloblasts deserve further study to help determine if there are other relevant clinical, morphologic, and cytogenetic discriminators.

References

References
1
Vardiman
JW
Harris
NL
Brunning
RD
The World Health Organization (WHO) classification of the myeloid neoplasms.
Blood.
100
2002
2292
2302
2
Jaffe
ES
Harris
NL
Stein
H
Vardiman
JW
World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues.
2001
IARC Press
Lyon, France
3
Kowal-Vern
A
Cotelingham
J
Schumacher
HR
The prognostic significance of proerythroblasts in acute erythroleukemia.
Am J Clin Path.
98
1992
34
40
4
Mazzella
FM
Kowal-Vern
A
Shrit
MA
Wibowo
AL
et al
Acute erythroleukemia evaluation of 48 cases with reference to classification, cell proliferation, cytogenetics, and prognosis.
Am J Clin Path.
110
1998
590
598
5
Foucar
K
Bone Marrow Pathology.
2001
ASCP Press
Chicago, IL
6
McKenna
RW
Allison
PM
Diagnosis, classification, and course of myelodysplastic syndromes.
Clin Lab Med.
10
1990
683
706