Excerpt from Agnogenic Myeloid Metaplasia With Myelofibrosis

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Background

Agnogenic myeloid metaplasia (AMM), first described by Heuck in 1879, is a clonal disorder arising from the neoplastic transformation of early hematopoietic stem cells.^{1, 2, 3, 4} Agnogenic myeloid metaplasia is categorized as a chronic myeloproliferative disorder, along with chronic myelogenous leukemia (CML), polycythemia vera, and essential thrombocytosis.⁵ The disorder is characterized by anemia,, bone marrow fibrosis, extramedullary hematopoiesis, leukoerythroblastosis, teardrop-shaped red blood cells (RBCs) in peripheral blood, and hepatosplenomegaly.

For excellent patient education resources, visit eMedicine's Blood and Lymphatic System Center and Cancer and Tumors Center. Also, see eMedicine's patient education article Anemia.

Related eMedicine topics:
Myelodysplastic Syndrome
Myeloproliferative Disease

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Pathophysiology

In patients with agnogenic myeloid metaplasia, the hematopoietic system is most affected. Other organ systems may be involved by extramedullary hematopoiesis.

Clonality studies in patients with agnogenic myeloid metaplasia demonstrate that myeloid cells arise from clonal stem cells; however, bone marrow fibroblasts and, sometimes, T cells are polyclonal. The cause of the excessive marrow fibrosis observed in agnogenic myeloid metaplasia remains unclear. Platelets, megakaryocytes, and monocytes are thought to secrete several cytokines, such as transforming growth factor beta (TGF-β), platelet-derived growth factor (PDGF), interleukin-1 (IL-1), epidermal growth factor (EGF), and basic fibroblast growth factor (bFGF), which may result in fibroblast formation and extracellular matrix proliferation. In addition, endothelial proliferation and growth of capillary blood vessels in the bone marrow are observed and may be a result of TGF-β and bFGF production.

Neoangiogenesis is a hallmark feature of chronic myeloproliferative disorders. Approximately 70% of patients with agnogenic myeloid metaplasia have substantial increases in bone marrow microvessel density. Neoangiogenesis in agnogenic myeloid metaplasia is noted in both medullary and extramedullary hematopoiesis. Increased serum vascular endothelial growth factor levels have been postulated as the underlying mechanism for increased angiogenesis.

Frequency

United States

Agnogenic myeloid metaplasia is an uncommon disease, with an annual incidence of approximately 0.5-1.5 cases per 100,000 individuals.

International

The worldwide incidence of agnogenic myeloid metaplasia is unknown.

Mortality/Morbidity

The main causes of death in patients with agnogenic myeloid metaplasia are infection, hemorrhage, cardiac failure, postsplenectomy complications, and transformation to acute leukemia.

• Leukemic transformation occurs in approximately 20% of patients with agnogenic myeloid metaplasia within the first 10 years. Renal failure, hepatic failure, and thrombosis have also been reported as causes of death.
• The median length of survival is approximately 3.5-5.5 years from diagnosis, with a range of 1-15 years.
• The 5-year survival rate is approximately half that expected for age- and sex-matched controls. Less than 20% of patients are expected to be alive at 10 years.⁶

Race

• Agnogenic myeloid metaplasia appears to be more common in white people than in individuals of other races.
• An increased prevalence rate of agnogenic myeloid metaplasia has been noted in Ashkenazi Jews.

Sex

A slight male preponderance appears to exist for agnogenic myeloid metaplasia; however, in younger children, girls are affected twice as frequently as boys.

Age

• Agnogenic myeloid metaplasia characteristically occurs in individuals older than 50 years. The median age at diagnosis is approximately 65 years.
• Agnogenic myeloid metaplasia has been reported in persons in all phases of life, from neonates to octogenarians.
• Approximately 22% of affected patients are younger than 56 years. Agnogenic myeloid metaplasia usually occurs in children in the first 3 years of life.

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