Prognosis of primary myelofibrosis
- Ayalew Tefferi, MD
Ayalew Tefferi, MD
- Professor of Medicine and Hematology
- Mayo Medical School
Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by the dysregulated proliferation of megakaryocytes and granulocytes in the bone marrow resulting in ineffective erythropoiesis, the production of cytokines within the marrow microenvironment, and the reactive deposition of fibrous connective tissue (reticulin or collagen) in the bone marrow, often with osteosclerosis. In later fibrotic stages, the peripheral blood demonstrates teardrop-shaped red cells (ie, dacrocytes), nucleated red blood cells, and early myeloid forms (ie, a triad termed leukoerythroblastosis), and extramedullary hematopoiesis results in hepatomegaly and splenomegaly. PMF has had numerous names in the past, including agnogenic myeloid metaplasia, myelofibrosis with myeloid metaplasia, and chronic idiopathic myelofibrosis.
The related myeloproliferative neoplasms essential thrombocythemia (ET) and polycythemia vera (PV) can both undergo delayed disease transformation into a fibrotic state called post-ET myelofibrosis (post-ET MF) or post-PV MF, respectively. The conversion rates after 10 to 20 years of disease are less than 5 percent for ET and approximately 10 to 20 percent for PV. PMF, post-ET MF, and post-PV MF are all referred to as myelofibrosis (MF).
The prognosis of PMF will be reviewed here. An overview of the myeloproliferative neoplasms, as well as discussions of treatment, pathogenetic mechanisms, clinical manifestations, and diagnosis of PMF, are presented separately. (See "Overview of the myeloproliferative neoplasms" and "Clinical manifestations and diagnosis of primary myelofibrosis" and "Management of primary myelofibrosis" and "Pathogenetic mechanisms in primary myelofibrosis".)
In an epidemiologic study of patients within Olmsted County, Minnesota, the three-year survival rate was 52 percent . Longer survival times have been reported in several non-population-based studies, including the series used for constructing the International Prognostic Scoring System (IPSS) for PMF, in which the median survival was reported to be 69 months .
A number of prognostic models are available for assessing prognosis in PMF [2-10]. The most recent and internationally recognized is the DIPSS Plus for PMF, described below. Their use in risk stratification for treatment decisions is presented separately. (See "Management of primary myelofibrosis".)To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Mesa RA, Silverstein MN, Jacobsen SJ, et al. Population-based incidence and survival figures in essential thrombocythemia and agnogenic myeloid metaplasia: an Olmsted County Study, 1976-1995. Am J Hematol 1999; 61:10.
- Cervantes F, Dupriez B, Pereira A, 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; 113:2895.
- Dupriez B, Morel P, Demory JL, et al. Prognostic factors in agnogenic myeloid metaplasia: a report on 195 cases with a new scoring system. Blood 1996; 88:1013.
- Cervantes F, Barosi G, Demory JL, et al. Myelofibrosis with myeloid metaplasia in young individuals: disease characteristics, prognostic factors and identification of risk groups. Br J Haematol 1998; 102:684.
- Dingli D, Schwager SM, Mesa RA, et al. Prognosis in transplant-eligible patients with agnogenic myeloid metaplasia: a simple CBC-based scoring system. Cancer 2006; 106:623.
- Elliott MA, Verstovsek S, Dingli D, et al. Monocytosis is an adverse prognostic factor for survival in younger patients with primary myelofibrosis. Leuk Res 2007; 31:1503.
- Tefferi A, Huang J, Schwager S, et al. Validation and comparison of contemporary prognostic models in primary myelofibrosis: analysis based on 334 patients from a single institution. Cancer 2007; 109:2083.
- Vener C, Fracchiolla NS, Gianelli U, et al. Prognostic implications of the European consensus for grading of bone marrow fibrosis in chronic idiopathic myelofibrosis. Blood 2008; 111:1862.
- Tam CS, Kantarjian H, Cortes J, et al. Dynamic model for predicting death within 12 months in patients with primary or post-polycythemia vera/essential thrombocythemia myelofibrosis. J Clin Oncol 2009; 27:5587.
- Morel P, Duhamel A, Hivert B, et al. Identification during the follow-up of time-dependent prognostic factors for the competing risks of death and blast phase in primary myelofibrosis: a study of 172 patients. Blood 2010; 115:4350.
- Passamonti F, Cervantes F, Vannucchi AM, et al. A dynamic prognostic model to predict survival in primary myelofibrosis: a study by the IWG-MRT (International Working Group for Myeloproliferative Neoplasms Research and Treatment). Blood 2010; 115:1703.
- Passamonti F, Cervantes F, Vannucchi AM, et al. Dynamic International Prognostic Scoring System (DIPSS) predicts progression to acute myeloid leukemia in primary myelofibrosis. Blood 2010; 116:2857.
- Hussein K, Huang J, Lasho T, et al. Karyotype complements the International Prognostic Scoring System for primary myelofibrosis. Eur J Haematol 2009; 82:255.
- Tefferi A, Meyer RG, Wyatt WA, Dewald GW. Comparison of peripheral blood interphase cytogenetics with bone marrow karyotype analysis in myelofibrosis with myeloid metaplasia. Br J Haematol 2001; 115:316.
- Tam CS, Abruzzo LV, Lin KI, et al. The role of cytogenetic abnormalities as a prognostic marker in primary myelofibrosis: applicability at the time of diagnosis and later during disease course. Blood 2009; 113:4171.
- Hussein K, Pardanani AD, Van Dyke DL, et al. International Prognostic Scoring System-independent cytogenetic risk categorization in primary myelofibrosis. Blood 2010; 115:496.
- Caramazza D, Begna KH, Gangat N, et al. Refined cytogenetic-risk categorization for overall and leukemia-free survival in primary myelofibrosis: a single center study of 433 patients. Leukemia 2011; 25:82.
- Tefferi A, Siragusa S, Hussein K, et al. Transfusion-dependency at presentation and its acquisition in the first year of diagnosis are both equally detrimental for survival in primary myelofibrosis--prognostic relevance is independent of IPSS or karyotype. Am J Hematol 2010; 85:14.
- Patnaik MM, Caramazza D, Gangat N, et al. Age and platelet count are IPSS-independent prognostic factors in young patients with primary myelofibrosis and complement IPSS in predicting very long or very short survival. Eur J Haematol 2010; 84:105.
- Gangat N, Caramazza D, Vaidya R, et al. DIPSS plus: a refined Dynamic International Prognostic Scoring System for primary myelofibrosis that incorporates prognostic information from karyotype, platelet count, and transfusion status. J Clin Oncol 2011; 29:392.
- Tefferi A, Lasho TL, Jimma T, et al. One thousand patients with primary myelofibrosis: the mayo clinic experience. Mayo Clin Proc 2012; 87:25.
- Tefferi A, Vaidya R, Caramazza D, et al. Circulating interleukin (IL)-8, IL-2R, IL-12, and IL-15 levels are independently prognostic in primary myelofibrosis: a comprehensive cytokine profiling study. J Clin Oncol 2011; 29:1356.
- Barbui T, Carobbio A, Finazzi G, et al. Elevated C-reactive protein is associated with shortened leukemia-free survival in patients with myelofibrosis. Leukemia 2013; 27:2084.
- Tefferi A, Lasho TL, Huang J, et al. Low JAK2V617F allele burden in primary myelofibrosis, compared to either a higher allele burden or unmutated status, is associated with inferior overall and leukemia-free survival. Leukemia 2008; 22:756.
- Guglielmelli P, Barosi G, Specchia G, et al. Identification of patients with poorer survival in primary myelofibrosis based on the burden of JAK2V617F mutated allele. Blood 2009; 114:1477.
- Tefferi A, Guglielmelli P, Larson DR, et al. Long-term survival and blast transformation in molecularly annotated essential thrombocythemia, polycythemia vera, and myelofibrosis. Blood 2014; 124:2507.
- Rumi E, Harutyunyan AS, Pietra D, et al. CALR exon 9 mutations are somatically acquired events in familial cases of essential thrombocythemia or primary myelofibrosis. Blood 2014.
- Vannucchi AM, Lasho TL, Guglielmelli P, et al. Mutations and prognosis in primary myelofibrosis. Leukemia 2013; 27:1861.
- Guglielmelli P, Lasho TL, Rotunno G, et al. The number of prognostically detrimental mutations and prognosis in primary myelofibrosis: an international study of 797 patients. Leukemia 2014; 28:1804.
- Tefferi A, Lasho TL, Finke CM, et al. CALR vs JAK2 vs MPL-mutated or triple-negative myelofibrosis: clinical, cytogenetic and molecular comparisons. Leukemia 2014; 28:1472.
- Lundberg P, Karow A, Nienhold R, et al. Clonal evolution and clinical correlates of somatic mutations in myeloproliferative neoplasms. Blood 2014; 123:2220.
- Scott BL, Gooley TA, Sorror ML, et al. The Dynamic International Prognostic Scoring System for myelofibrosis predicts outcomes after hematopoietic cell transplantation. Blood 2012; 119:2657.
- Taylor UB, Bardeguez AD, Iglesias N, Gascon P. Idiopathic myelofibrosis in pregnancy: a case report and review of the literature. Am J Obstet Gynecol 1992; 167:38.
- Gotić M, Cvetković M, Bozanović T, Cemerikić V. [Successful treatment of primary myelofibrosis with thrombocytosis during pregnancy with alfa-interferon]. Srp Arh Celok Lek 2001; 129:304.
- Tulpule S, Bewley S, Robinson SE, et al. The management and outcome of four pregnancies in women with idiopathic myelofibrosis. Br J Haematol 2008; 142:480.
- International Working Group Scoring System
- - IPSS
- - Dynamic IPSS
- - DIPSS Plus
- Predicting leukemic transformation
- - Elevated cytokine levels
- - JAK2, calreticulin, and MPL mutational burden
- - Effect of other mutations
- Candidates for hematopoietic cell transplantation
- RISK STRATIFICATION FOR MANAGEMENT
- SUMMARY AND RECOMMENDATIONS