Document Detail

Primary myelofibrosis: 2013 update on diagnosis, risk-stratification, and management.
MedLine Citation:
PMID:  23349007     Owner:  NLM     Status:  MEDLINE    
DISEASE OVERVIEW: Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by stem cell-derived clonal myeloproliferation, abnormal cytokine expression, bone marrow fibrosis, anemia, splenomegaly, extramedullary hematopoiesis (EMH), constitutional symptoms, cachexia, leukemic progression, and shortened survival.
DIAGNOSIS: Diagnosis is based on bone marrow morphology. The presence of fibrosis, JAK2/MPL mutation, or +9/13q- cytogenetic abnormality is supportive but not essential for diagnosis. Prefibrotic PMF mimics essential thrombocythemia in its presentation and the distinction is prognostically relevant. Differential diagnosis of myelofibrosis should include chronic myeloid leukemia, myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia.
RISK STRATIFICATION: The Dynamic International Prognostic Scoring System-plus (DIPSS-plus) prognostic model for PMF can be applied at any point during the disease course and uses eight independent predictors of inferior survival: age >65 years, hemoglobin <10 g/dL, leukocytes >25 × 10⁹/L, circulating blasts ≥ 1%, constitutional symptoms, red cell transfusion dependency, platelet count <100 × 10⁹/L, and unfavorable karyotype (i.e., complex karyotype or sole or two abnormalities that include +8, -7/7q-, i(17q), inv(3), -5/5q-, 12p-, or 11q23 rearrangement). The presence of 0, 1, "2 or 3," and ≥ 4 adverse factors defines low, intermediate-1, intermediate-2, and high-risk disease with median survivals of approximately 15.4, 6.5, 2.9, and 1.3 years, respectively. A >80% two-year mortality is predicted by monosomal karyotype, inv(3)/i(17q) abnormalities, or any two of circulating blasts >9%, leukocytes ≥ 40 × 10⁹/L or other unfavorable karyotype. Most recently, mutations involving ASXL1, SRSF2, EZH2, and IDH1/2 or increased plasma IL-2R, IL-8, or serum-free light chain levels have been shown to adversely affect survival.
RISK-ADAPTED THERAPY: Observation alone is adequate for asymptomatic low/intermediate-1 risk disease. Allogeneic stem cell transplantation (ASCT) is often considered for high risk disease. Conventional or experimental drug therapy is reasonable for symptomatic intermediate-1 or intermediate-2 risk disease; however, ASCT is an acceptable treatment option for such patients in the presence of ASXL1 or other prognostically adverse mutations. Splenectomy and low-dose radiotherapy are used for drug-refractory splenomegaly. Radiotherapy is also used for the treatment of non-hepatosplenic EMH, PMF-associated pulmonary hypertension, and extremity bone pain.
Ayalew Tefferi
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  American journal of hematology     Volume:  88     ISSN:  1096-8652     ISO Abbreviation:  Am. J. Hematol.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-25     Completed Date:  2013-03-22     Revised Date:  2013-11-06    
Medline Journal Info:
Nlm Unique ID:  7610369     Medline TA:  Am J Hematol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  141-50     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Wiley Periodicals, Inc.
Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
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MeSH Terms
Antineoplastic Agents / therapeutic use
Bone Marrow / pathology
Decision Trees
Diagnosis, Differential
Drug Resistance, Neoplasm
Drugs, Investigational / therapeutic use
Janus Kinase 2 / genetics,  metabolism
Primary Myelofibrosis / diagnosis*,  genetics,  pathology,  therapy*
Receptors, Thrombopoietin / genetics,  metabolism
Repressor Proteins / genetics,  metabolism
Stem Cell Transplantation
Reg. No./Substance:
0/ASXL1 protein, human; 0/Antineoplastic Agents; 0/Drugs, Investigational; 0/Receptors, Thrombopoietin; 0/Repressor Proteins; 143641-95-6/MPL protein, human; EC protein, human; EC Kinase 2
Erratum In:
Am J Hematol. 2013 May;88(5):437-45

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