Current clinical strategies and emergent treatment landscapes in leukemic transformation of Philadelphia-negative myeloproliferative neoplasms.

Introduction: Transformation to acute myeloid leukemia (AML) of Philadelphia chromosome-negative (Ph-) chronic myeloproliferative neoplasms (MPN) represents a challenging medical concern and an unmet clinical need, since it charts a very poor outcome and a low rate of response to standard treatments with the exception of allogeneic hematopoietic stem cell transplantation (HSCT). Recent novel insights into the molecular disease pathways and the genomic features characterizing the transformation of Ph-MPN have led to new therapeutic individualized approaches with the potential to modify the clinical management of these difficult-to-treat patients. Areas covered: Literature review (MeSH headings/PubMed) of risk factors of MPNs progression and treatment options for transformed disease with traditional standard approaches, and novel and investigational agents was performed. One or combinations of related subject headings like transformed MPN, epigenetics, molecular alterations, HSCT, ruxolitinib, azacytidine, decitabine, gliterinib, novel agents, personalized therapy was screened. Informative papers were selected by the appropriate actual evidence and suggesting strategies for improving outcomes in the future. Expert opinion: Current and emerging treatments for transformed Ph-MPN, are presented. Novel targeted or experimental agents to be used both before HSCT, to induce blast-free state, or to modify the disease prognosis and improve survival and quality of life are critically reviewed.