eMedicine Specialties > Hematology > Stem Cells and Disorders

Erythroleukemia

Author: Beata Holkova, MD, Oncology Fellow, NIH/NCI, National Cancer Institute
Coauthor(s): Kenichi Takeshita, MD, Adjunct Associate Professor, Department of Medicine, Division of Hematology, New York University School of Medicine; Medical Director, Clinical Research and Development, Celgene; Asher A Chanan-Khan, MD, Assistant Professor, Department of Medicine, Division of Lymphoma and Bone Marrow Transplantation, Roswell Park Cancer Institute, State University of New York at Buffalo
Contributor Information and Disclosures

Updated: Nov 4, 2009

Introduction

Background

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 based on morphologic and cytochemical criteria (see image below).1

Bone marrow aspirate showing erythroblasts in a p...

Bone marrow aspirate showing erythroblasts in a patient with erythroleukemia. Courtesy of Maurice Barcos, MD, PhD, Department of Pathology, Roswell Park Cancer Institute, Buffalo, NY.

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Bone marrow aspirate showing erythroblasts in a p...

Bone marrow aspirate showing erythroblasts in a patient with erythroleukemia. Courtesy of Maurice Barcos, MD, PhD, Department of Pathology, Roswell Park Cancer Institute, Buffalo, NY.


Recent research

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.2 In the erythroleukemia and control groups, 50% and 41% of patients, respectively, had a history of the predisposing factor myelodysplastic syndrome (see Causes). Poor-risk cytogenetics were present in 61% of the erythroleukemia patients and in 38% of the control patients.

Remission and survival rates within the 2 groups were as follows:

  • Complete remission
    • Erythroleukemia patients: 62%
    • Control group: 58%
  • Median period of disease-free survival
    • Erythroleukemia patients: 32 weeks
    • Control group: 49 weeks
  • Median period of overall survival
    • Erythroleukemia patients: 36 weeks
    • Control group: 43 weeks

Following 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.

Pathophysiology

Erythroleukemia is a neoplastic proliferation of erythroid and myeloid precursors of bone marrow hematopoietic stem cells, even though a pure erythroid proliferation may occur on rare occasions.

Frequency

United States

Acute erythroleukemia accounts for 3-5% of all de novo AMLs and 20-30% of secondary leukemias. It is very rare in children.

Race

No racial predilection is known.

Sex

Occurrence has a slight male predominance.

Age

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 of life.1,3 Although rare in children, M6 AML has been reported in children from the newborn period through age 7 years.

Clinical

History

Upon presentation, signs and symptoms of erythroleukemia are usually nonspecific and result from decreased hematopoiesis from the replacement of bone marrow by leukemic cells. This results in anemia, thrombocytopenia, and leukopenia. Patients rarely present with symptoms lasting longer than 6 months, and they are usually diagnosed within 1-3 months after the onset of symptoms. The most common presenting symptoms are as follows:

  • Fatigue or malaise
  • Minimal-to-modest weight loss
  • Easy bruising
  • Fever
  • Bone or abdominal pain
  • Dyspnea
  • Meningeal signs and symptoms (very rare, only if leukemic involvement of CNS is present)
  • Diffuse joint pain (nonspecific in one third of patients)

Physical

  • Pallor (anemia)
  • Hemorrhage (thrombocytopenia)
    • Ecchymoses or petechiae
    • Gum bleeding
    • Epistaxis
    • Retinal hemorrhage
  • Fever and infection (neutropenia): Common sites include the respiratory tract, urinary tract, sinuses, perirectal area, and skin.
  • Hepatosplenomegaly (<25% cases)
  • Lymphadenopathy

Causes

De novo cases have no identifiable risk factors. The most common predisposing factors in secondary acute erythroleukemia are as follows:

  • Myelodysplastic syndrome (MDS) is a predisposing factor.
  • Ionizing radiation: Thorotrast, a radiographic contrast medium used in the 1940s, is associated with increased risk of erythroleukemia (latent period of 10-30 y after exposure).
  • Prior chemotherapy, such as with alkylating agents, is a predisposing factor. These agents may be used in the treatment of Hodgkin disease, multiple myeloma, bone marrow transplant, ovarian and breast cancer, and nonneoplastic disorders (eg, collagen-vascular disease).
  • Rare cases of familial erythroleukemia (autosomal dominant with variable penetrance) have been described, which manifest in the sixth decade of life.

More on Erythroleukemia

Overview: Erythroleukemia
Differential Diagnoses & Workup: Erythroleukemia
Treatment & Medication: Erythroleukemia
Follow-up: Erythroleukemia
Multimedia: Erythroleukemia
References
Further Reading
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References

  1. Mazzella FM, Alvares C, Kowal-Vern A, Schumacher HR. The acute erythroleukemias. Clin Lab Med. Mar 2000;20(1):119-37. [Medline].

  2. Santos FP, Faderl S, Garcia-Manero G, Koller C, Beran M, O'Brien S, et al. Adult acute erythroleukemia: an analysis of 91 patients treated at a single institution. Leukemia. Sep 10 2009;[Medline].

  3. Mazzella FM, Kowal-Vern A, Shrit MA, et al. Effects of multidrug resistance gene expression in acute erythroleukemia. Mod Pathol. Apr 2000;13(4):407-13. [Medline].

  4. Wang SA, Tang G, Fadare O, Hao S, Raza A, Woda BA, et al. Erythroid-predominant myelodysplastic syndromes: enumeration of blasts from nonerythroid rather than total marrow cells provides superior risk stratification. Mod Pathol. Nov 2008;21(11):1394-402. [Medline].

  5. Kowal-Vern A, Mazzella FM, Cotelingam JD, et al. Diagnosis and characterization of acute erythroleukemia subsets by determining the percentages of myeloblasts and proerythroblasts in 69 cases. Am J Hematol. Sep 2000;65(1):5-13. [Medline].

  6. McHayleh W, Sehgal R, Redner RL, Raptis A, Agha M, Natale J, et al. Mitoxantrone and etoposide in patients with newly diagnosed acute myeloid leukemia with persistent leukemia after a course of therapy with cytarabine and idarubicin. Leuk Lymphoma. Oct 8 2009;[Medline].

  7. Bennett JM, Catovsky D, Daniel MT, et al. Proposed revised criteria for the classification of acute myeloid leukemia. A report of the French-American-British Cooperative Group. Ann Intern Med. Oct 1985;103(4):620-5. [Medline].

  8. Cuneo A, Van Orshoven A, Michaux JL, et al. Morphologic, immunologic and cytogenetic studies in erythroleukaemia: evidence for multilineage involvement and identification of two distinct cytogenetic-clinicopathological types. Br J Haematol. Jul 1990;75(3):346-54. [Medline].

  9. Harris NL, Jaffe ES, Diebold J, et al. World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997. J Clin Oncol. Dec 1999;17(12):3835-49. [Medline].

  10. Jaffe ES, Harris NL, Stein H, Vardiman JW, eds. Acute myeloid leukaemia not otherwise categorised. In: WHO Classification of Tumours. Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. IARC Press: Lyon;2001:91-105.

  11. Leith CP, Kopecky KJ, Godwin J, et al. Acute myeloid leukemia in the elderly: assessment of multidrug resistance (MDR1) and cytogenetics distinguishes biologic subgroups with remarkably distinct responses to standard chemotherapy. A Southwest Oncology Group study. Blood. May 1 1997;89(9):3323-9. [Medline].

  12. Mayer RJ, Davis RB, Schiffer CA, et al. Intensive postremission chemotherapy in adults with acute myeloid leukemia. Cancer and Leukemia Group B. N Engl J Med. Oct 6 1994;331(14):896-903. [Medline].

  13. Mazzella FM, Kowal-Vern A, Shrit MA, et al. Acute erythroleukemia: evaluation of 48 cases with reference to classification, cell proliferation, cytogenetics, and prognosis. Am J Clin Pathol. Nov 1998;110(5):590-8. [Medline].

  14. Mehta J, Powles R, Treleaven J, et al. Long-term follow-up of patients undergoing allogeneic bone marrow transplantation for acute myeloid leukemia in first complete remission after cyclophosphamide-total body irradiation and cyclosporine. Bone Marrow Transplant. Oct 1996;18(4):741-6. [Medline].

  15. Sonneveld P. Multidrug resistance in haematological malignancies. J Intern Med. May 2000;247(5):521-34. [Medline].

  16. Thomas ED, Buckner CD, Banaji M, et al. One hundred patients with acute leukemia treated by chemotherapy, total body irradiation, and allogeneic marrow transplantation. Blood. Apr 1977;49(4):511-33.

  17. Vardiman J. Proposed WHO Classification of Neoplastic Diseases of Hematopoietic and Lymphoid Tissues (Acute Leukemias and Myeloid Disorders). Am J Surg Path. 1997;21:114-21.

  18. Willman CL. The prognostic significance of the expression and function of multidrug resistance transporter proteins in acute myeloid leukemia: studies of the Southwest Oncology Group Leukemia Research Program. Semin Hematol. Oct 1997;34(4 Suppl 5):25-33. [Medline].

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Keywords

erythroleukemia, acute myeloid leukemia, AML leukemia, acute myelogenous leukemia, AML, leukemia, acute myeloid leukaemia, acute leukemia prognosis, neoplastic proliferation, erythroid precursor, myeloid precursor, M6 AML, Di Guglielmo disease, Di Guglielmo syndrome

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Contributor Information and Disclosures

Author

Beata Holkova, MD, Oncology Fellow, NIH/NCI, National Cancer Institute
Beata Holkova, MD is a member of the following medical societies: American College of Physicians and American Society of Hematology
Disclosure: Nothing to disclose.

Coauthor(s)

Kenichi Takeshita, MD, Adjunct Associate Professor, Department of Medicine, Division of Hematology, New York University School of Medicine; Medical Director, Clinical Research and Development, Celgene
Kenichi Takeshita, MD is a member of the following medical societies: American Society of Hematology
Disclosure: Nothing to disclose.

Asher A Chanan-Khan, MD, Assistant Professor, Department of Medicine, Division of Lymphoma and Bone Marrow Transplantation, Roswell Park Cancer Institute, State University of New York at Buffalo
Asher A Chanan-Khan, MD is a member of the following medical societies: American College of Physicians, American Medical Association, and American Society of Hematology
Disclosure: Nothing to disclose.

Medical Editor

David Aboulafia, MD, Medical Director, Bailey-Boushay House; Clinical Professor, Department of Medicine, Division of Hematology, University of Washington
David Aboulafia, MD is a member of the following medical societies: American College of Physicians, American Medical Association, American Medical Directors Association, American Society of Hematology, Infectious Diseases Society of America, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Troy H Guthrie, Jr, MD, Director of Cancer Institute, Baptist Medical Center
Troy H Guthrie, Jr, MD is a member of the following medical societies: American Federation for Medical Research, American Medical Association, American Society of Hematology, Florida Medical Association, Medical Association of Georgia, and Southern Medical Association
Disclosure: Nothing to disclose.

CME Editor

Rajalaxmi McKenna, MD, FACP, Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD, Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Thomas Jefferson University
Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, and New York Academy of Sciences
Disclosure: Nothing to disclose.

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