How I Treat How I treat myelofibrosis

Myelofibrosis (MF), formerly known as idiopathic MF, MF with myeloid metaplasia, or agnogeneic myeloid metaplasia, is one of the classical BCR-ABL1-negative chronic myeloproliferative neoplasms (MPNs), a group also including essential thrombocythemia (ET) and polycythemia vera (PV). Either appearing de novo (primary MF [PMF]) or following a previous ET or PV (post-ET or post-PVMF), the disease is essentially the same. MF is a clonal proliferation of a pluripotent hematopoietic stem cell, in which the abnormal cell population releases several cytokines and growth factors in the bone marrow that lead to marrow fibrosis and stroma changes and colonizes extramedullary organs such as the spleen and liver. Discovery of the V617F mutation of the Janus kinase (JAK)2 gene in 60% of patients with PMF or post-ETMF and 95% of those with post-PV MF represented an important step in the understanding of the pathogenesis of MF. Mutations in the thrombopoietin receptor gene (MPL) were subsequently found in 3% to 8% of patients with PMF and post-ETMF, whereas mutations in the calreticulin gene (CALR) have been observed in half of patients with PMF and post-ET MF lacking JAK2 andMPLmutations. Mutations shared by other myeloid neoplasms are found in some patients. However, the genetic trigger of MF is unknown. MF mostly affects elderly people. At present, there is no curative treatment other than allogeneic hemopoietic stem cell transplantation (allo-SCT), which can be applied to aminority of patients. Therefore, treatment remains essentially palliative and aimed at controlling disease symptoms and complications and improving the patients’ quality of life. The therapeutic landscape of MF has changed with the introduction of the JAK inhibitors. In the present article, I will discuss the treatment options currently available for MF, how I have incorporated the new prognostic information to the clinical decision-making process, and how I have integrated novel therapeutic modalities in my practice. The discussion on the more relevant clinical scenarios of MF will be preceded by a representative case study to illustrate how I decide the treatment strategy for the main clinical situations of this complex disease.