Refractory anemia with excess blasts (RAEB) in 2003

2003-11-01   Antonio Cuneo , Gianluigi Castoldi 

1.Hematology Section, Department of Biomedical Sciences, University of Ferrara, Corso Giovecca 203, Ferrara, Italy

Clinics and Pathology

Phenotype stem cell origin

RAEB is a clonal disorder originating from a totipotent stem cell or from a multipotent myeloid progenitor cell, characterized by ineffective hemopoiesis and diserythropoiesis. The blast cell present in the BM are usually CD34+ and express myeloid markers (i.e. CD33 and/or CD13).

Epidemiology

There are few data on the epidemiology of RAEB, which may account for 20-30% of all MDS cases. MDS is predominantly diagnosed in the elderly population. The global incidence of all MDS was comprised between 3,5 and 12,6 new cases / year / per 100,000 in some studies. The incidence may rise from 0,5 MDS cases per year in the 40 years age-group to 89 cases per year in the >80 age-group.

Clinics

RAEB usually presents with hypercellular bone marrow (BM) with 5-20% blasts (5-9% in RAEB-1 and 10-19% in RAEB-2) and cytopenias of various degree. Blast cells (<20%) can be present in the peripheral blood.
The patient may be asymptomatic or, alternatively he/she may suffer from BM failure-related symptoms.

Cytology

Criteria for the recognition of dysplastic features of BM cells were published by the FAB group. Dyserythropoiesis includes megaloblastoid changes of erythroid precursors, multinuclearity, nuclear fragmentation, unstained area in the cytoplasm (dysemoglobinization). Dysgranulocytopoiesis include hypogranular neutrophils, the pseudo-Pelger anomaly of neutrophils. Micromegakaryocytes, large mononuclear forms and multiple separated nuclei are major signs of dysmegakaryocytopoiesis.

Pathology

The bone biopsy may be useful in some cases of MDS with BM fibrosis and allows for the demonstration of the so called "abnormal localization of immature precursors" (ALIP) which may represent a prognostic factor.

Treatment

Treatment of this condition in the elderly patient is largely supportive, including blood transfusion in patients with symptomatic anemia. Anemic patients with low serum erythropoietin (EPO) levels may benefit of the administration of rHu-EPO. Low dose cytarabine can be used to reduce the burden of blasts. Myeloablative regimens including anthracyclines and cytarabine in conventional or high doses can be used in high-risk patients under 60 years. Allogeneic bone marrow transplantation may offer a chance of cure in young patients.

Evolution

This is an oligoblastic leukemia, carrying a 20-40% probability of evolving into leukemia. In a study approximately 25% of the patient developed acute myeloid leukemia (AML) within 18 months.
The probability of RAEB to transform into AML is lower in the RAEB-1 group (approximately 50% of the patients develop acute leukemia within 6 years) than in the RAEB-2 group (approximately 50% at 18 months with overt leukemia).

Prognosis

Median survival of RAEB falls in the 1-2 year range. The best outcome is usually observed in RAEB-1.
Chromosomal abnormalities have independent prognostic significance and are to be included in risk assessment at diagnosis. Favourable cytogenetic features are normal karyotype, 5q- or 20q- isolated; unfavourable features are complex karyotype (i.e. 3 or more clonal anomalies) and abnormalities of chromosome 7q; other abnormalities identify patients in the intermediate cytogenetic-risk group.

Bibliography

Pubmed IDLast YearTitleAuthors
116944002001Myelodysplastic syndromes: recent advances.Alessandrino EP et al
69529201982Proposals for the classification of the myelodysplastic syndromes.Bennett JM et al
87226831996Cytogenetics of myelodysplastic syndromes.Fenaux P et al
23198061990Prognostic factors of myelodysplastic syndromes--a simplified 3-D scoring system.Goasguen JE et al
90587301997International scoring system for evaluating prognosis in myelodysplastic syndromes.Greenberg P et al
78850351995Myelodysplastic syndromes and acute myeloid leukemia with 17p deletion. An entity characterized by specific dysgranulopoïesis and a high incidence of P53 mutations.Lai JL et al
78137081994Life expectancy in primary myelodysplastic syndromes: a prognostic score based upon histopathology from bone marrow biopsies of 569 patients.Maschek H et al
117536032001Clinical importance of interphase cytogenetics detecting occult chromosome lesions in myelodysplastic syndromes with normal karyotype.Rigolin GM et al
84642271993Clinical implications of chromosomal abnormalities in 401 patients with myelodysplastic syndromes: a multicentric study in Japan.Toyama K et al
122391372002The World Health Organization (WHO) classification of the myeloid neoplasms.Vardiman JW et al

Summary

Note

This disorder is part of the heterogeneous category of myelodysplastic syndrome (MDS). According to the FAB classification of MDS, RAEB includes those patients with 5-20% blasts in the bone marrow (BM). Because the severity of the disease largely depends on the percentage of blasts in the BM, two categories of RAEB were recognised by the WHO classification, i.e. RAEB-1 and RAEB-2, with 5-9% and 10-19% blasts, respectively.
In this card, the FAB classification will be used, because the majority of available data on cytogenetic anomalies was derived from studies published before WHO classification.See also Myelodysplastic syndrome with excess blasts (WHO 2016)

Citation

Antonio Cuneo ; Gianluigi Castoldi

Refractory anemia with excess blasts (RAEB) in 2003

Atlas Genet Cytogenet Oncol Haematol. 2003-11-01

Online version: http://atlasgeneticsoncology.org/haematological/1105/refractory-anemia-with-excess-blasts-(raeb)-in-2003

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