VIKAS GUPTA (TORONTO)
TREATMENT STRATEGIES FOR BLAST PHASE OF MPN
The Philadelphia-negative myeloproliferative neoplasms (MPNs), including essential
thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis, are related clonal
hematopoietic cell diseases characterized by an overproduction of mature myeloid cells.
Transformation to blast phase (MPN-BP) defined as ≥20% myeloblasts in peripheral blood (PB)
or bone marrow (BM), occurs in approximately 5%-20% of patients with MPN. Outcomes of
MPN-BP are dismal, with typical survival of several months and little to no improvement over
the past decade.
Biologically, patients with MPN-BP are significantly distinct from de novo AML. Patients with
MPN-BP have a complex genetic profile with a higher frequency of adverse-risk cytogenetic
abnormalities as well as mutations known to affect the outcomes of AML patients such as
TP53, RAS-signaling pathway mutations, and ASXL1 and SRSF2 mutations. The role of intensive
induction chemotherapy is limited to selected patients, who are able to undergo allogeneic
hematopoietic cell transplantation (HCT). There is limited benefit of intensive induction
chemotherapy in patients who are not candidates for HCT. These patients may benefit from
treatment with Hypomethylating agents (HMA). Newer approaches such as combination of
HMA with venetoclax or other targeted therapies in MPN-BP appear encouraging, however
lack prospective evaluation. Moreover, there is urgent need to develop meaningful response
criteria in MPN-BP to facilitate the comparison between different treatment strategies.