ABSTRACT
Category of classic, non-chronic myeloid leukemia (CML) myeloproliferative neoplasms (BCR-ABL1-negative) include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) [1]. These three disorders are often positive for JAK2 mutations or mutations involving CALR, MPL, LNK, CBL, TET2, ASHL1, IDH, IKZF1, DNMT3A, TP53, SF3B1, or SRSF2 [2–7]. PMF is an uncommon clonal stem cell disorder characterized by the autonomous proliferation of myeloid and granulocytic elements with panmyelosis, marked and diffuse bone marrow (BM) fibrosis (due to cytokine-induced non-neoplastic fibroblast proliferation), leukoerythroblastic blood picture with teardrop poikilocytosis, and extramedullary hematopoiesis with progressive hepatosplenomegaly [1,8–11]. Patients with history of PV or ET and myelofibrosis are classified as post-polycythemic myelofibrosis (post-PV-MF) and post-ET-MF, respectively. Patients with PMF are usually diagnosed late in life (median age is 66 years) and usually present with symptoms of BM failure such as fatigue and dyspnea (due to ineffective erythropoiesis leading to severe anemia), bleeding (associated with thrombocytopenia), night sweats, and fever. Other common clinical manifestations of PMF include prominent hepatosplenomegaly, thrombosis, pruritus, and bone pain. Extramedullary hematopoiesis (“myeloid metaplasia”) is the main cause of organomegaly. The BM is hypercellular with panmyelosis, diffuse reticulin fibrosis and clusters of highly atypical (often bizarre and hyperchromatic) megakaryocytes. WHO criteria for PMF are presented in Table 32.1. The discovery of the JAK2 mutation and the development of JAK2 inhibitors (such as Ruxolitinib) provide clinicians with a new effective treatment option for patients with PMF. Treatment options include also allogeneic stem cell transplant (ASCT).
