myelofibrosis
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Etiology
- idiopathic
- secondary
- lymphoma (Hodgkin's & non-Hodgkin's lymphoma)
- hairy cell leukemia
- acute leukemia (lymphocytic & myelocytic)
- multiple myeloma
- chronic myelogenous leukemia
- polycythemia rubra vera
- carcinoma metastatic to the bone marrow
- systemic mastocytosis
- infectious diseases
- hyperparathyroidism, especially secondary to renal failure
- systemic lupus erythematosus (rare)
- thorium dioxide (Thorotrast) exposure
- renal osteodystrophy
Pathology
- clonal stem cell proliferation, especially of megakaryocytes
- excess secretion of growth factors producing reactive fibrosis in the bone marrow, i.e. fibroblast growth factor
- bone marrow fibrosis
- ineffective, extramedullary hematopoiesis
- circulating immature hematopoietic precursors especially nucleated RBC
- massive splenomegaly
- hepatomegaly
- occurs with myeloid metaplasia
Genetics
- associated with defects in JAK2 gene (overactivity ?)
Clinical manifestations
- fever, chills, night sweats, malaise
- early satiety, weight loss
- hepatomegaly, splenomegaly (massive)
Laboratory
- complete blood count (CBC)
- reticulocyte count is low
- peripheral blood smear -> leukoerythroblastic blood smear
- serum erythropoietin (< 500 uM/mL is deficient)
- bone marrow biopsy: marrow fibrosis
- JAK2 gene mutation
- CALR gene mutation
- MPL gene mutation
Complications
- evolution to acute myeloid leukemia (AML) (5-20%)[1][3]
- risk factors for transformation
- age > 65 years
- fever, night sweats
- weight loss of 10% or more
- blood hemoglobin < 10 g/dL
- leukocyte count > 25,000/uL
- circulating blasts in blood >= 1%[1][4]
- arterial thromboembolism & venous thromboembolism[1]
- iron overload from repeated transfusions is common
- portal hypertension
- death fom bone marrow failure, transformation to acute leukemia, or complications of portal hypertension
Management
- also see myeloid metaplasia
- supportive therapy, treatment of symptomatic anemia (blood hemoglobin < 10 g/dL)[3]
- androgens (danazol)
- erythropoietin
- transfusions as needed
- iron overload from repeated transfusions is common
- may be life-threatening
- long-term chelation therapy may be beneficial when frequent repeated transfusions are needed
- epoetin alfa or darbepoetin alfa if serum erythropoietin < 500 mU/mL
- cytotoxic therapy often limited by cytopenias
- interferon-alpha
- hydroxyurea may be beneficial for symptoms of splenomegaly & for constitutional symptoms[1]
- allogeneic stell cell transplantation
- patients < 55-60 years of age
- variable results
- only treatment with potential for cure[1]
- not candidates for stell cell transplantation & platelet count > 50,000/uL
- ruxolitinib, a JAK1 & JAK2 inhibitor, 1st FDA-approved drug for treatment of myelofibrosis[1]
- risk of thromboembolism & of evolution to AML not affected
- benefits appear independent of JAK2 mutation[1]
- fedratinib in another JAK2 inhibitor
- ruxolitinib, a JAK1 & JAK2 inhibitor, 1st FDA-approved drug for treatment of myelofibrosis[1]
- avoid splenectomy
- associated with hemorrhagic & thrombotic complications, increased risk of progression to AML & has no benefit for survival[1]
- observation is appropriate for low-risk patients[1]
- median survival in low-risk patients is 11 years[1]
More general terms
More specific terms
Additional terms
References
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2006, 2012, 2015, 2018, 2022.
Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022 - ↑ Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 682
- ↑ 3.0 3.1 3.2 Geriatrics at your Fingertips, 13th edition, 2011 Reuben DB et al (eds) American Geriatric Society
- ↑ 4.0 4.1 Cervantes F, Dupriez B, Pereira A, Passamonti F et al New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood. 2009 Mar 26;113(13):2895-901 PMID: https://www.ncbi.nlm.nih.gov/pubmed/18988864
- ↑ NEJM Knowledge+ Question of the Week. July 3, 2018 https://knowledgeplus.nejm.org/question-of-week/1107/
- ↑ National Comprehensive Cancer Network Myeloproliferative Neoplasms Clinical Practice Guidelines (NCCN, 2022) Medscape. September 30, 2022 https://reference.medscape.com/viewarticle/978759