MMMF is an unusual clonal disorder sometimes also known as idiopathic myelofibrosis. Gradual fibrosis of the marrow space with extramedullary hematopoiesis is the typical course. Splenomegaly is common. An examination of the peripheral blood film shows the presence of nucleated red blood cells and teardrop forms that are the characteristic leukoerythroblastic findings. The incidence of MMMF is unknown, but it tends to be a disease of the elderly, with an average age of approximately 60 years.
The malignant transformation appears to occur at the level of the stem cells, with a dense collagen fibrosis developing in the marrow space. There is no known etiology. The clinical manifestations relate to either the presence of splenomegaly or the consequences of anemia or other cytopenia. Rarely, sites of extramedullary hematopoiesis appearing in the pulmonary, gastrointestinal, central nervous, or genitourinary systems have been the presenting finding for occult MMMF.
As noted, the peripheral blood smear typically shows teardrop poikilocytes, confirming the leukoerythroblastic blood picture. Nucleated red blood cells and immature myeloid elements are also frequently seen. There are variable effects on circulating white cells and platelets. The diagnosis is made on the basis of the characteristic clinical findings and the presence of fibrotic marrow, which can be more accurately assessed histologically with the aid of a reticulin stain. Many conditions can lead to secondary fibrosis of the marrow, including lymphoma, carcinoma, and chronic diseases such as TB and histoplasmosis, as well as some of the other myeloproliferative syndromes as previously mentioned, and these need to be ruled out before a primary diagnosis is made.
Therapy for MMMF is unsatisfactory. In general, a conservative management strategy is adopted, although some authors have suggested that chemotherapy early in the course of disease can be beneficial. Symptomatic patients generally require symptom-directed therapy. Thus, anemia is treated with transfusion, as well as complete evaluation for other coexistent disorders such as nutrient deficiencies. Androgen stimulation is also frequently used.
Symptoms of splenomegaly, such as early satiety, are treated with measures to induce reduction in splenic size. Chemotherapy with hydroxyurea, P, and other agents has been used with some, at least short-term, success. Interferon has been used successfully to shrink splenomegaly but has frequently resulted in worsened cytopenias. Splenic radiation has also been used, but usually a short duration of response is seen. Splenectomy is a controversial issue. It is indicated for patients with severe thrombocytopenia, uncontrolled hemolysis, or painful splenomegaly that is refractory to other methods of control. However, there is a significant perioperative mortality rate. The prognosis for MMMF is worse than that for essential thrombocythemia and polycythemia vera. Average survival is approximately 5 years.
- Acute Leukemias
- Myeloproliferative Disorders
Revision date: June 20, 2011
Last revised: by Jorge P. Ribeiro, MD