myelofibrosis
Table of Contents
myelofibrosis
introduction
- a myeloproliferative disorder in which the proliferation of an abnormal type of bone marrow stem cell results in the replacement of the marrow with collagenous connective tissue fibers and thus fibrosis
- mainly in those over 50 years age
- associated with activation of the Janus kinase pathway resulting in increased signalling in some cytokines and growth factors involved in haematopoiesis and immune functions
- overall survival from diagnosis without stem cell transplant is usually 2 - 11 years
- survival of patients with primary myelofibrosis is dependent on the underlying mutually exclusive mutation1):
- MPL exon 10 mutation ⇒ 60% 5yr survival, 30% 10 yr survival (median survival 8 yrs, 25% die in 1st 2 yrs )
- JAK2-V617F mutation ⇒ 80% 5yr survival, 50% 10 yr survival (median survival 11 yrs)
- CALR exon 9 mutation ⇒ 95% 5yr survival, ~88% 10 yr survival (median survival 21 yrs), lower risk of thrombosis
aetiology
- primary
- 50-60% due to acquired Janus kinase 2 gene JAK2 (V617F) mutation
- 20-30% due to somatically acquired calreticulin gene CALR exon 9 mutation 2)
- 5-10% due to acquired thrombopoietin receptor gene MPL exon 10 mutation
- ~10% have none of the above mutations
- secondary to:
-
- commonly occurs in the spent phase of PCV, possibly in response to the medication hydroxyurea poisoning the marrow and blood
-
clinical features
- progressive pancytopenia
- anaemia with bizarre tear-drop shaped RBC's
- thrombocytopenia and hence bleeding, bruising
- neutropenia with increased immature neutrophils and basophilia
- patients often have hepatosplenomegaly due to liver and spleen becoming haematopoietic tissues (splenomegaly may result in the spleen weighing > 4kg!) and poikilocytosis
- risk of splenic infarction, splenic trauma, perisplenitis
- occasionally, extramedullary haematopoiesis in the lungs may result in pulmonary hypertension (PAH)
- night sweats
- abdominal discomfort
- anorexia
- weight loss
- susceptibility to infections and reactivation of herpes zoster
- gouty arthritis that is secondary to hyperuricaemia
- occasionally acute febrile neutrophilic dermatosis (Sweet syndrome):
- fever accompanied by painful, maculopapular, violaceous lesions on the trunk, arms, legs, and face
treatment options
- supportive:
- folic acid
- allopurinol
- blood transfusions
- possible adjuncts:
- alpha-interferon
- hydroxyurea - useful to suppress the number of circulating cells
- thalidomide
- lenalidomide
-
- ruxolitinib
- marketed in Aust from 2013 as Jakavi
- selective inhibitor of Janus kinase I and II
- appears to reduce spleen size or prevent it enlarging further
- 50% reduction in disease associated symptoms compared with 5% for placebo, but these return to baseline within 1 week of stopping Rx, and serious withdrawl symptoms make gradual dose reduction a recommendation.
- BUT 82% developed anaemia, 67% thrombocytopenia and 15% neutropenia hence need to monitor FBE
- dose 15-25mg bd
- radiotherapy to spleen
- splenectomy
- allogeneic stem cell transplantation
myelofibrosis.txt · Last modified: 2014/11/24 10:12 by 127.0.0.1