Myeloproliferative neoplasms (MPN) are a heterogeneous group of clonal hematopoietic stem cell disorders characterized clinically by the proliferation of one or more hematopoietic lineage(s). The classical Philadelphia-chromosome (Ph)-negative MPNs include polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). The Asian Myeloid Working Group (AMWG) comprises representatives from fifteen Asian centers experienced in the management of MPN. This consensus from the AMWG aims to review the current evidence in the risk stratification and treatment of Ph-negative MPN, to identify management gaps for future improvement, and to offer pragmatic approaches for treatment commensurate with different levels of resources, drug availabilities and reimbursement policies in its constituent regions. The management of MPN should be patient-specific and based on accurate diagnostic and prognostic tools. In patients with PV, ET and early/prefibrotic PMF, symptoms and risk stratification will guide the need for early cytoreduction. In younger patients requiring cytoreduction and in those experiencing resistance or intolerance to hydroxyurea, recombinant interferon-α preparations (pegylated interferon-α 2A or ropeginterferon-α 2b) should be considered. In myelofibrosis, continuous risk assessment and symptom burden assessment are essential in guiding treatment selection. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in MF should always be based on accurate risk stratification for disease-risk and post-HSCT outcome. Management of classical Ph-negative MPN entails accurate diagnosis, cytogenetic and molecular evaluation, risk stratification, and treatment strategies that are outcome-oriented (curative, disease modification, improvement of quality-of-life).
The Acute Promyelocytic Leukemia Asian Consortium analyzed a contemporaneous cohort of newly-diagnosed APL patients treated with and without frontline arsenic trioxide (ATO) in six centers. The objectives were to define the impact of ATO on early deaths and relapses, and its optimal positioning in the overall treatment strategy. In a 21.5-year period, 324 males and 323 females at a median age of 45.5 (range: 18.1-91.8) years (low/intermediate risk, N=448; high-risk, N=199) were treated. Regimens included frontline all-trans retinoic acid (ATRA)/chemotherapy and maintenance with/without ATO (N=436); ATRA/intravenous-ATO/chemotherapy (ATRA/i.v.-ATO; N=61); and ATRA/oral-ATO/ascorbic acid with ATO maintenance (oral-AAA; N=150). The ATRA/chemotherapy group, compared with the ATO-containing (ATRA/i.v.-ATO and oral-AAA) groups, had significantly more frequent early deaths within 60 days (8.3% versus 3.3%; P=0.05); inferior 60-day survival (91.7% versus 98.4%/96%; P<0.001); inferior 5-year relapse-free survival (RFS) (76.9% versus 92.8%/97.8%; P<0.001) and inferior 5-year overall survival (OS) (84.6% versus 91.4%/92.3%; P=0.03). Addition of oral-ATO maintenance could partly mitigate the inferior 5-year RFS resulting from omission of ATO during induction (ATRA/chemotherapy/non-ATO maintenance versus ATRA/chemotherapy/ATO maintenance versus ATRA/i.v.-ATO versus oral-AAA: 71.1% versus 87.9% versus 92.8% versus 97.8%, P<0.001). The favorable survival impacts of ATO were observed in both low/intermediate-risk and high-risk patients, so that conventional risks (high leucocyte and low platelet counts) were overcome. Therefore, ATO decreased early deaths, improved 60-day survival, and resulted in significantly superior RFS and OS. Its benefits were most obvious in frontline treatment, but were still observed during maintenance. (ClinicalTrials.gov Identifier: NCT04251754).