Myelofibrosis
Questions Received:
Responses:
Please tell me about myelofibrosis. What is it, what causes it and what are the treatments and prognosis? Is it a pre-cancerous condition and if so what kind?
12th June 1999
Myelofibrosis is the name given to an increase in the amount of fibrous tissue within the marrow spaces inside bones and accompanying problems such as enlargement of the spleen and disorders of blood formation. It is more common in people over the age of 50 years. Myelofibrosis can occur on its own, but more usually there is an associated increase in the production of certain types of blood cells, constituting the so-called myeloproliferative diseases. There are several of these: polycythaemia vera, chronic myeloid leukemia, essential thrombocythaemia, and agnogenic myeloid metaplasia. Bone marrow biopsies and clinical signs and symptoms enable these conditions to be differentiated (Georgii et al, 1996; Michiels, 1996; Thiele et al, 1999). Each has its own pattern of progression and outcome in terms of life expectancy (Michiels et al, 1999):
Essential Thrombocythemia - characterised by increased numbers and clustering of enlarged megakaryocytes (the cells that produce platelets) in a relatively normal or slightly more cellular bone marrow - fibrosis does not generally occur in this condition
Polycythemia Vera - characterised by increased numbers and clustering of enlarged megakaryocytes and increased production of red blood cells in a more cellular bone marrow with hyperplasia of dilated sinuses. A minority of patients show marrow fibrosis in the early stages, and later the majority do
Agnogenic Myeloid Metaplasia or Idiopathic Myelofibrosis - abnormal proliferation of megakaryocytes and granulocytes (Michiels et al, 1999). The bone marrow is dominated by atypical, enlarged and immature megakaryocytes.
Generally the initial causes of marrow fibrosis are unknown, although in a minority of cases there may be environmental triggers such as exposure to benzene, carbon tetrachloride, phosphorus, or high levels of radiation. Bone marrow biopsies in patients with myelofibrosis reveal increased numbers of megakaryocytes which in addition to over-producing platelets also secrete growth factors, peptides that are used as signalling molecules in the body and which in this case stimulate the fibrocytes in the marrow to produce more fibrous material (Martyre, 1995; Tefferi and Silverstein, 1996).
Treatments for myeloproliferative diseases depend on which condition is being treated, and include bone marrow transplantation and treatment with drugs such as aspirin and platelet-lowering agents (Tefferi, 1998; Michiels et al, 1999). In some patients with essential thrombocythemia or polycythemia vera, treatment may not be required or is limited to phlebotomy. Life expectancy is normal in essential thrombocythemia, but significantly shortened in agnogenic myeloid metaplasia and idiopathic myelofibrosis. Although the different cell types which are produced in these myelofibrotic diseases have normal structure and function, in some cases they are being produced in excess as a result of a change in the processes which control cell division and in that sense resemble cancer.
References
Georgii, A., Buhr, T., Buesche, G., Kreft, A., and Choritz, H. (1996) Classification and staging of Ph-negative myeloproliferative disorders by histopathology from bone marrow biopsies. Leuk Lymphoma, 22 Suppl 1, 15-29 (Sep).
Martyre, M.C. (1995) TGF-beta and megakaryocytes in the pathogenesis of myelofibrosis in myeloproliferative disorders. Leuk Lymphoma, 20(1-2), 39-44 (Dec).
Michiels, J.J. (1996) The myeloproliferative disorders. An historical appraisal and personal experiences. Leuk Lymphoma, 22 Suppl 1, 1-14 (Sep).
Michiels, J.J., Kutti, J., Stark, P., et al (1999) Diagnosis, pathogenesis and treatment of the myeloproliferative disorders essential thrombocythemia, polycythemia vera and essential megakaryocytic granulocytic metaplasia and myelofibrosis. Netherlands Journal of Medicine, 54(2), 46-62 (Feb).
Tefferi, A. (1998) The Philadelphia chromosome negative chronic myeloproliferative disorders: a practical overview. Mayo Clinical Proceedings, 73(12), 1177-1184 (Dec).
Tefferi, A., and Silverstein, M.N. (1996) Current perspective in agnogenic myeloid metaplasia. Leuk Lymphoma, 22 Suppl 1, 169-171 (Sep).
Thiele, J., Kvasnicka, H.M., Diehl, V., Fischer, R., and Michiels, J. (1999) Clinicopathological diagnosis and differential criteria of thrombocythemias in various myeloproliferative disorders by histopathology, histochemistry and immunostaining from bone marrow biopsies. Leuk Lymphoma, 33(3-4), 207-218 (Apr).
Family diagnosed with myelofibrosis. Several years ago he had been diagnosed with polycythaemia vera. Is extreme lethargy and loss of muscle mass associated with this condition?
19th October 1999
Yes, weakness, fatigue, and weight-loss are recognised symptoms of myelofibrosis.
Have you ever heard of cats having myelofibrosis? My 10 year old cat was just diagnosed with this.
2nd August 2000
We do not normally answer questions about disease processes in species other than the human. However, our veterinary colleague Jereme Darke has advised us that myelofibrosis does indeed occur in cats, for example in association with acute myelogenous leukaemias, myelodysplastic syndromes, and feline leukaemic virus (FELV). As in the human, myelofibrosis in cats is characterised by proliferation of immature connective tissue cells in the marrow cavity and increased synthesis of the fibrous protein collagen. The blood-forming cells may be affected, and there may also be changes in the liver, spleen and lymph nodes. Secondary myelofibrosis occurs as a non-specific reaction to prolonged bone marrow damage (Chandler, Gaskell, and Gaskell, 1994).
Reference
Chandler, Gaskell, and Gaskell (1994) Feline medicine and therapeutics (2nd edition). Blackwell Scientific Publications (Chapter 3, pp184-185).