Blast phase myeloproliferative neoplasm: contemporary review and 2024 treatment algorithm

Abstract

Leukemic transformation in myeloproliferative neoplasms (MPN), also referred to as “blast-phase MPN”, is the most feared disease complication, with incidence estimates of 1–4% for essential thrombocythemia, 3–7% for polycythemia vera, and 9–13% for primary myelofibrosis. Diagnosis of MPN-BP requires the presence of ≥20% circulating or bone marrow blasts; a lower level of excess blasts (10–19%) constitutes “accelerated phase” disease (MPN-AP). Neither “intensive” nor “less intensive” chemotherapy, by itself, secures long-term survival in MPN-BP. Large-scale retrospective series have consistently shown a dismal prognosis in MPN-BP, with 1- and 3-year survival estimates of <20% and <5%, respectively. Allogeneic hematopoietic stem cell transplant (AHSCT) offers the possibility of a >30% 3-year survival rate and should be pursued, ideally, while the patient is still in chronic phase disease. The value of pre-transplant bridging chemotherapy is uncertain in MPN-AP while it is advised in MPN-BP; in this regard, we currently favor combination chemotherapy with venetoclax (Ven) and hypomethylating agent (HMA); response is more likely in the absence of complex/monosomal karyotype and presence of TET2 mutation. Furthermore, in the presence of an IDH mutation, the use of IDH inhibitors, either alone or in combination with Ven-HMA, can be considered. Pre-transplant clearance of excess blasts is desired but not mandated; in this regard, additional salvage chemotherapy is more likely to compromise transplant eligibility rather than improve post-transplant survival. Controlled studies are needed to determine the optimal pre- and post-transplant measures that target transplant-associated morbidity and post-transplant relapse.

2024 update on allogeneic hematopoietic stem cell transplant for myelofibrosis: A review of current data and applications on risk stratification and management

“…Options are HMA‐based regimen or if patient is eligible for intensive induction then intensive induction followed by transplant. ORR after inductions were 39%–59% with OS after HSCT at 3 years 18%–33% 45 …”

Assessment of Total Antioxidant Capacity, 8-Hydroxy-2′-deoxy-guanosine, the Genetic Landscape, and Their Associations in BCR::ABL-1-Negative Chronic and Blast Phase Myeloproliferative Neoplasms

“…Classical myeloproliferative neoplasms (MPNs), i.e., polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are clonal stem cell disorders defined by the excessive production of functionally mature and terminally differentiated myeloid cells as a consequence of the presence of mutually exclusive activating mutations in genes involved in the JAK/STAT signaling pathway, namely, the Janus Kinase 2 ( JAK2 ), calreticulin ( CALR ), and thrombopoietin receptor ( MPL/TPOR ) genes, respectively [ 1 , 2 , 3 , 4 ]. Apart from their phenotypic mimicry, the absence of the BCR::ABL-1 molecular marker, and their predisposition to develop primarily thrombotic events and bleeding episodes, PV and ET can progress to secondary myelofibrosis (MF), and all MPNs can undergo leukemic transformation to secondary acute myeloid leukemia (sAML or MPN blast phase) [ 1 , 2 , 5 , 6 ].…”

Momelotinib for myelofibrosis: our 14 years of experience with 100 clinical trial patients and recent FDA approval

“…In addition, the clinical course of the disease in MF is complicated by progressive anemia, extramedullary hematopoiesis with marked splenomegaly and hepatomegaly, constitutional symptoms, and cachexia. Causes of death in MF include disease transformation into acute myeloid leukemia [ 7 ].…”