The Prognostic Significance of Proerythroblasts in Acute Erythroleukemia

Abstract

Erythroleukemia is a heterogeneous disorder that can have an excess of myeloblasts or proerythroblasts in the setting of dyserythropoiesis. The French-American-British classification, established in 1976 and subsequently revised, allows only for the diagnosis of erythroleukemias whose immature elements are predominated by myeloid blasts, previously described as DiGuglielmo's syndrome. However, there is another form of erythroleukemia, in which the predominant immature elements are proerythroblasts, called DiGuglielmo's disease. To clarify this issue, 23 cases of erythroleukemia were reviewed and classified: 10 with a myeloblast predominance and 13 with a proerythroblastic predominance. These two forms of erythroleukemia can be distinguished on the basis of quantitative and qualitative morphologic features. When there were 30% or more proerythroblasts, calculated by dividing the total erythroid component into the proerythroblasts, there were few to no myeloblasts, no Auer rods, and increased cytoplasmic vacuoles; and myeloperoxidase staining was negative. The malignant proerythroblasts had increased block and blush periodic acid-Schiff positivity. The most frequent chromosomal abnormalities involved chromosomes 5 and 7. The patients with DiGuglielmo's disease had a median survival time of 2 months (range, 0.06 to 9 months), compared to a median of 16 months (range, 2 to 48 months), in patients with DiGuglielmo's syndrome. The erythroleukemia with the preponderance of proerythroblasts had a worse prognosis because many of the individuals did not survive long enough to respond to the therapy initiated. Erythroleukemia with 30% or more proerythroblasts should be included in the French-American-British classification because it behaves clinically and appears morphologically as an acute leukemia rather than a myelodysplastic syndrome.

Acute erythremic myelosis (true erythroleukaemia): a variant of AML FAB-M6

“…Past medical histories are not provided in most of the previously reported cases, but it is interesting to note that two of the cases in one of the series also had a past history of myelodysplasia. 19 In addition, chromosome 5 and 7 losses or deletions, often associated with myelodysplastic syndromes, were present in one of our cases, paradoxically in the case without a history of myelodysplasia. Thirteen of 15 previously reported cases with cytogenetic data had losses and/or deletions in the long arms of chromosomes 5 and/or 7, and several cases had lost material from both of these chromosomes.…”

Pure erythroid leukemia: a reassessment of the entity using the 2008 World Health Organization classification

“…However, in the study referred by the 2008 WHO for the definition of PEL consisting of eight cases of minimally differentiated erythroleukemia, the inclusion criteria were Z50% immature erythroblasts with o10% 'differentiating' forms. 5 In contrary, Mazzella and colleagues 6,15,16 have consistently used 30% pronormoblasts of erythroid precursors as the cutoff to define PEL. In 2002, Domingo-Claros et al 17 studied 62 cases of acute erythroid neoplastic proliferation by using the 2001 WHO criteria.…”

“…[3][4][5][6] In 1992, KowalVern et al 6 proposed including erythroleukemias with Z30% pronormoblasts, the most immature recognizable erythroid precursors, as a subtype of AML. They also proposed modifying the FAB system by renaming FAB-M6 as M6a, and cases that fit with Di Guglielmo disease as M6b.…”

Erythroleukemia: a need for a new definition

“…8 The difference of prognosis between de novo and secondary leukemia is related to karyotype abnormalities. The percentage of pronormoblasts seems an important factor of survival according to Kowal-Vern et al, 13 with a mean survival of 34 months in AML6a, 3.5 months in AML6b and 10.5 months for AML6c. However, for other authors, more than the percentage of erythroblasts, cytogenetic abnormalities correlate with the rate of CR.…”