Therapy of Philadelphia-negative myeloproliferative neoplasms in the blast phase

Abstract

All four Philadelphia negative myeloproliferative neoplasms: essential thrombocythemia, polycythemia vera, pre-fibrotic myelofibrosis, and myelofibrosis, are at risk of transforming to blast phase disease. The risk is highest in the case of myelofibrosis and amounts to c.20%. In the case of essential thrombocythemia, the transformation rate is 1%, and in polycythemia vera it is 5–10%. The prognosis of patients during the blast crisis is poor, with a median survival time of a few months. For patients who qualify for intensive therapy, the basis of treatment are cycles analogous to those in acute myeloid leukemia and allotransplantation of hematopoietic stem cells. In the remaining patients, hypomethylating drugs such as azacitidine and decitabine can be used. Some hope has been raised by new drugs approved for the treatment of patients with acute myeloid leukemia such as venetoclax, IDH1 and IDH2 inhibitors ivosidenib and enasidenib. It is very important that patients with myeloproliferative neoplasms, especially those with myelofibrosis, properly assess the risk of blast transformation and qualify them early enough for allotransplantation of hematopoietic stem cells. New prognostic scales taking into account molecular factors can be very helpful in the assessment. This article discusses the risk factors of blast transformation, and prognostic scales as well as therapies that can be used during the blast crisis, including new drugs.