New approaches in the treatment of myelofibrosis

Abstract

Myelofibrosis with myeloid metaplasia (MMM) is a chronic clonal neoangiogenesis disorder characterized by bone marrow fibrosis and neoangiogensis with extramedullary hematopoiesis. Identification of prognostic factors associated with MMM have not impacted the treatment of the disease, which continues to be palliative with the exception of allogeneic stem cell transplantation (SCT) for potential long-term disease-free survival in selected patients. Additional insights into the pathophysiology of MMM have resulted in the use of novel therapeutic strategies in the treatment of this disease. The rationale for the investigation of these agents in MMM and the status of clinical trials with various modalities such as angiogenesis inhibitors (e.g., thalidomide), tyrosine kinase inhibitors (e.g., imatinib mesylate), farnesyl transferase inhibitors (e.g., R115777), and other agents are reviewed, in addition to the potential roles of autologous and allogeneic SCT.

The European Consensus on grading of bone marrow fibrosis allows a better prognostication of patients with primary myelofibrosis

“…[11][12][13][14][15][16][17] At present, primary myelofibrosis treatment is essentially palliative; allogenic stem cell transplantation is increasingly being used, and newer drugs (such as anti-JAK2-targeted drugs) are being tested in such patients. [17][18][19] Although mortality is less frequent among the patients undergoing reduced-intensity conditioning allogenic stem cell transplantation than in those undergoing conventional allogenic stem cell transplantation, there is still some associated mortality and morbidity and the prognostic stratification of primary myelofibrosis patients is thus important when making treatment decisions. In a previous study, we tested the prognostic significance of the European Consensus on grading of bone marrow fibrosis system in primary myelofibrosis patients, and compared it with all of the validated prognostic scoring systems (Mayo, 12 Dingli, 20 Cervantes, 13 and Dupriez 14 ).…”

Outcome of Transplantation for Myelofibrosis

“…The median age at diagnosis is 67 years, and many elderly patients are managed with supportive care. Erythropoietin has been helpful for the treatment of anemia in some patients, and hydroxyurea has been used to control the white blood cell count(10). Thalidomide combined with prednisone has been tested in a Phase II trial; sixty-two percent of patients had improvement in anemia(11).…”

Prognostic implications of the European consensus for grading of bone marrow fibrosis in chronic idiopathic myelofibrosis

“…[1][2][3] Its main clinicopathological characteristics are progressive anemia, leukocytosis or leukopenia, increased levels of circulating CD34 ϩ hematopoietic progenitor cells, constitutional symptoms, bone marrow fibrosis with neovascularization, and marked splenomegaly with extramedullary hematopoiesis. 1,2,[4][5][6] The patients' median age at diagnosis is 60 years, 7 and transformation to acute leukemia occurs in 15% of cases with an extremely poor prognosis.…”

“…1,2,[4][5][6] The patients' median age at diagnosis is 60 years, 7 and transformation to acute leukemia occurs in 15% of cases with an extremely poor prognosis. 3,[8][9] A number of prognostic scoring systems (PSSs) based on clinical variables (platelet count, leukocyte count, monocyte count, circulating blasts, hemoglobin level, systemic symptoms, and hepato/splenomegaly) have been proposed as means of selecting high-risk patients at diagnosis who may be eligible for intensive treatments. 1,4,7,[10][11][12] Three of these (the Mayo, 12 Cervantes, 10 and Dupriez 11 PSSs) have been compared in the same series of patients, and were all found to have significant prognostic value, although the results of the Mayo PSS 12 were the most solid.…”