z-logo
open-access-imgOpen Access
Accelerated Phase of Myeloproliferative Neoplasms
Author(s) -
Omar Shahin,
Helen T. Chifotides,
Prithviraj Bose,
Lucia Masárová,
Srđan Verstovšek
Publication year - 2021
Publication title -
acta haematologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.574
H-Index - 56
eISSN - 1421-9662
pISSN - 0001-5792
DOI - 10.1159/000512929
Subject(s) - ruxolitinib , myelofibrosis , medicine , oncology , myeloproliferative neoplasm , leukocytosis , myeloid , hematopoietic stem cell transplantation , transplantation , gastroenterology , bone marrow
Background: Myeloproliferative neoplasms (MPNs) can transform into blast phase MPN (leukemic transformation; MPN-BP), typically via accelerated phase MPN (MPN-AP), in ∼20–25% of the cases. MPN-AP and MPN-BP are characterized by 10–19% and ≥20% blasts, respectively. MPN-AP/BP portend a dismal prognosis with no established conventional treatment. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the sole modality associated with long-term survival. Summary: MPN-AP/BP has a markedly different mutational profile from de novo acute myeloid leukemia (AML). In MPN-AP/BP, TP53 and IDH1/2 are more frequent, whereas FLT3 and DNMT3A are rare. Higher incidence of leukemic transformation has been associated with the most aggressive MPN subtype, myelofibrosis (MF); other risk factors for leukemic transformation include rising blast counts above 3–5%, advanced age, severe anemia, thrombocytopenia, leukocytosis, increasing bone marrow fibrosis, type 1 CALR -unmutated status, lack of driver mutations (negative for JAK2, CALR, or MPL genes), adverse cytogenetics, and acquisition of ≥2 high-molecular risk mutations ( ASXL1, EZH2, IDH1/2, SRSF2 , and U2AF1 Q157 ). The aforementioned factors have been incorporated in several novel prognostic scoring systems for MF. Currently, elderly/unfit patients with MPN-AP/BP are treated with hypomethylating agents with/without ruxolitinib; these regimens appear to confer comparable benefit to intensive chemotherapy but with lower toxicity. Retrospective studies in patients who acquired actionable mutations during MPN-AP/BP showed positive outcomes with targeted AML treatments, such as IDH1/2 inhibitors, and require further evaluation in clinical trials. Key Messages: Therapy for MPN-AP patients represents an unmet medical need. MF patients, in particular, should be appropriately stratified regarding their prognosis and the risk for transformation. Higher-risk patients should be monitored regularly and treated prior to progression to MPN-BP. MPN-AP patients may be treated with hypomethylating agents alone or in combination with ruxolitinib; also, patients can be provided with the option to enroll in rationally designed clinical trials exploring combination regimens, including novel targeted drugs, with an ultimate goal to transition to transplant.

The content you want is available to Zendy users.

Already have an account? Click here to sign in.
Having issues? You can contact us here