Updated: Dec 29, 2015
  • Author: Beata Holkova, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Giovanni Di Guglielmo first described erythroleukemia in the early twentieth century, and the disorder is often still referred to as acute Di Guglielmo syndrome. It is classified as an M6 subtype of acute myelogenous leukemia (AML) in the French-American-British (FAB) classification system on the basis of morphologic and cytochemical criteria. [1]



Erythroleukemia is a neoplastic proliferation of erythroid and myeloid precursors of bone marrow hematopoietic stem cells. [2] On rare occasions, however, a pure erythroid proliferation may occur.



De novo cases of erythroleukemia are not associated with any identifiable risk factors. The most common predisposing factors in secondary acute erythroleukemia are as follows:



Acute erythroleukemia accounts for 3-5% of all de novo AMLs and 20-30% of secondary leukemias. The incidence of erythroleukemia increases in people older than 50 years. Mazzella et al described 2 peaks, one in the seventh decade of life and a second, smaller peak in the fourth decade. [1, 3] Although very rare in children, M6 AML has been reported in children from the newborn period through age 7 years. Occurrence has a slight male predominance. No racial predilection is known.



Patients with acute erythroleukemia have a poor prognosis. Problems encountered in the treatment of acute erythroleukemia include primary induction failure, relapse, and the toxicity of chemotherapeutic agents.

Many factors influence patients’ responses to chemotherapy and their duration of remission, including the following [4] :

  • Findings from cytogenetic evaluation affect the prognosis.

  • No specific chromosome abnormalities are associated with this subtype.

  • Multidrug resistant phenotype (positive Pgp expression) is associated with a poor prognosis.

  • Determining the myeloblast-to-erythroblast ratio at diagnosis helps to predict prognosis; a higher ratio is associated with a favorable prognosis.

In a study of 91 patients with newly diagnosed erythroleukemia, Santos et al compared the disease’s prognosis with that of patients in a control group suffering from other subtypes of AML. [4] A history of the predisposing factor MDS was present in 50% of the patients in the erythroleukemia group and 41% of the patients in the control group. Poor-risk cytogenetics were present in 61% of the erythroleukemia patients and 38% of the control patients.

Complete remission rates were 62% in the erythroleukemia group and 58% in the control group. The median period of disease-free survival was 32 weeks for erythroleukemia patients and 49 weeks for control subjects. The median period of overall survival was 36 weeks for erythroleukemia patients and 43 weeks for control subjects.

After carrying out a multivariate analysis, the report’s authors concluded that erythroleukemia is not an independent risk factor in disease-free and overall survival, and that well-known AML prognostic factors should guide treatment decisions.

Remission can be achieved in many patients when treated with the standard myeloid protocol (ie, cytarabine [cytosine arabinoside; ara-C] with anthracycline). Kowal-Vern et al reported that subtypes characterized by predominance of proerythroblasts are not targeted by conventional AML protocols and suggested that this might be related to the poor outcome observed in these patients. [5]

Multidrug resistance gene (ie, MDR1) expression correlates with unfavorable cytogenetic aberrations and is responsible for poor response to chemotherapy and short survival time. Patients with refractory or relapsed erythroleukemia may be tested for Pgp (ie, MDR1 product). MDR modulators (eg, cyclosporin A, quinidine, verapamil, PSC 833) are being used in a clinical trial setting to overcome this resistance. [3]

A less favorable outcome may be observed in elderly patients, in patients with secondary erythroleukemia (usually after treatment with alkylating agents), and in patients with unfavorable cytogenetics.

Furthermore, patients with the distinct entity of pure erythroid leukemia (PEL) may have an unusually poor prognosis. PEL is characterized as a neoplastic erythroid hyperproliferation with maturation arrest. E-cadherin is the most sensitive and specific marker for immature erythroblasts and is helpful in distinguishing PEL from other erythroid proliferations. The newly assigned World Health Organization (WHO) categories fail to capture the distinct features of PEL; the phenotype of PEL correlates with a very complex karyotype and an extremely aggressive clinical course. Among 18 patients with PEL, median survival was only 3 months (range 1-7 mo). [6]


Patient Education

Patients should be educated about the signs of febrile neutropenia and thrombocytopenia. The long-term adverse effects of chemotherapeutic agents must be clearly explained, and issues related to chemotherapy-associated infertility (eg, sperm banking) must be presented and discussed. Procedure-related adverse effects and failure to obtain informed consent should also be addressed.