Primary myelofibrosis: 2012 update on diagnosis, risk stratification, and management

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Abstract

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 myelogenous 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 × 10 9/L, circulating blasts ≥1%, constitutional symptoms, red cell transfusion dependency, platelet count <100 × 10 9/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 ∼ 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 × 10 9/L or other unfavorable karyotype. Risk-adapted therapy: Observation alone is adequate for asymptomatic low/intermediate-1 risk disease. Allogeneic stem cell transplantation or experimental drug therapy is considered for intermediate-2/ high risk disease. Conventional or experimental drug therapy is reasonable for symptomatic intermediate-1 risk disease. 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.

Original languageEnglish (US)
Pages (from-to)1017-1026
Number of pages10
JournalAmerican Journal of Hematology
Volume86
Issue number12
DOIs
StatePublished - Dec 2011

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Primary Myelofibrosis
Risk Management
Extramedullary Hematopoiesis
Investigational Therapies
Splenomegaly
Karyotype
Radiotherapy
Leukemia, Myelomonocytic, Chronic
Essential Thrombocythemia
Drug Therapy
Cachexia
Myelodysplastic Syndromes
Stem Cell Transplantation
Splenectomy
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Platelet Count
Pulmonary Hypertension
Acute Myeloid Leukemia
Chromosome Aberrations
Anemia

ASJC Scopus subject areas

  • Hematology

Cite this

Primary myelofibrosis : 2012 update on diagnosis, risk stratification, and management. / Tefferi, Ayalew.

In: American Journal of Hematology, Vol. 86, No. 12, 12.2011, p. 1017-1026.

Research output: Contribution to journalArticle

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abstract = "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 myelogenous 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 × 10 9/L, circulating blasts ≥1{\%}, constitutional symptoms, red cell transfusion dependency, platelet count <100 × 10 9/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 ∼ 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 × 10 9/L or other unfavorable karyotype. Risk-adapted therapy: Observation alone is adequate for asymptomatic low/intermediate-1 risk disease. Allogeneic stem cell transplantation or experimental drug therapy is considered for intermediate-2/ high risk disease. Conventional or experimental drug therapy is reasonable for symptomatic intermediate-1 risk disease. 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.",
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