Prevention and treatment of transformation of myeloproliferative neoplasms to acute myeloid leukemia.

Philadelphia-chromosome negative myeloproliferative neoplasms (MPN) are hematopoietic stem disorders with a risk of progression to an accelerated phase (AP) or blast phase (BP) that is influenced by clinical, pathological, cytogenetic, and molecular variables.

Overall survival of patients with MPN-AP/BP is limited with current treatment approaches, particularly in those patients who cannot receive an allogeneic hematopoietic stem cell transplant (allo-HCT).

In addition, long-term survival with allo-HCT is predominantly seen in chronic-phase MPN, which suggests that the ideal time for intervention may be before the MPN evolves to AP/BP.

In this review we focus on the risk factors for progression to MPN-AP/BP, identification of high-risk chronic-phase MPN, potential early-intervention strategies, and considerations around the timing of allo-HCT.

We also summarize current survival outcomes of patients with MPN-AP/BP, discuss the uncertainty around how to best gauge response to therapy, and outline clinical trial considerations for this population of patients. Lastly, we highlight future directions in the management of high-risk MPN.