Myeloproliferative Neoplasms (MPNs) Management

Classification and Diagnosis

The National Comprehensive Cancer Network recommends classifying myeloproliferative neoplasms into Philadelphia-negative classical MPNs, including polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF) 1
Diagnosis of MPNs requires meeting specific WHO criteria, including molecular testing for driver mutations (JAK2, CALR, or MPL), as recommended by the National Comprehensive Cancer Network 2
The presence of specific mutations has prognostic significance, with CALR mutations generally conferring better outcomes than JAK2 mutations or "triple-negative" status, according to the National Comprehensive Cancer Network 2

For PV and ET, high-risk patients are defined as those with age >60 years or history of previous thrombosis, as stated by the National Comprehensive Cancer Network 3
Additional risk factors for PV and ET include extreme thrombocytosis, cardiovascular risk factors, and leukocytosis, as noted by the National Comprehensive Cancer Network 4, 3
For myelofibrosis, the International Prognostic Scoring System (IPSS) should be used at diagnosis, and the Dynamic IPSS (DIPSS) during the disease course, as recommended by the Journal of Clinical Oncology 5, 3

The National Comprehensive Cancer Network recommends that low-risk PV patients receive phlebotomy to maintain hematocrit <45% and low-dose aspirin (81-100 mg daily) 3, 4
High-risk PV patients should receive phlebotomy, low-dose aspirin, and cytoreductive therapy with hydroxyurea as first-line, according to the National Comprehensive Cancer Network 3, 6
For ET, low-risk patients should be observed with regular monitoring, and high-risk patients should receive cytoreductive therapy with hydroxyurea as first-line, as recommended by the National Comprehensive Cancer Network 2, 3
The Journal of Clinical Oncology recommends that patients with primary myelofibrosis (PMF) who are low-risk or intermediate-1 risk should be observed if asymptomatic, or receive ruxolitinib if symptomatic 4, 6
Intermediate-2 or high-risk PMF patients should receive allogeneic stem cell transplantation if eligible, or ruxolitinib for symptomatic splenomegaly, as stated by the Journal of Clinical Oncology 4, 5, 6

The Journal of Clinical Oncology recommends that patients with splanchnic vein thrombosis receive low molecular weight heparin followed by long-term oral anticoagulation, with a target INR of 2.0-3.0 7
For pregnant patients with MPNs, the Journal of Clinical Oncology recommends low-dose aspirin throughout pregnancy, and consideration of low molecular weight heparin for high-risk patients 8
If platelet count ≥1,500 × 10^9/L, interferon-alpha should be considered, as noted by the Journal of Clinical Oncology 8

The National Comprehensive Cancer Network recommends regular assessment of blood counts to monitor response and detect cytopenias, as well as use of the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) to assess symptom burden 3, 2
Monitoring for disease progression with bone marrow examination should be done as clinically indicated, as stated by the National Comprehensive Cancer Network 4

The National Comprehensive Cancer Network recommends Ruxolitinib as the first-line JAK2 inhibitor for intermediate-2 or high-risk myelofibrosis with symptomatic splenomegaly, and the preferred second-line therapy for polycythemia vera patients who are resistant or intolerant to hydroxyurea 9
Ruxolitinib improves overall survival in intermediate-2 or high-risk myelofibrosis compared to placebo and best available therapy, despite extensive crossover in trials 10, 11
The drug provides rapid and durable reduction in splenomegaly and constitutional symptoms regardless of JAK2 mutation status, with a 51% response rate in splenomegaly and 42% response rate in constitutional symptoms 11
Ruxolitinib is effective independent of JAK2V617F, CALR, or MPL mutational status 11
In a minority of patients, ruxolitinib reduces JAK2 allelic burden and improves bone marrow fibrosis 10, 12

Ruxolitinib is approved for second-line treatment of polycythemia vera after hydroxyurea resistance or intolerance, with 60% of patients achieving hematocrit control and 49% achieving a ≥50% reduction in total symptom score 9, 11, 13, 14
Spleen volume reduction ≥35% was achieved in 38% of ruxolitinib patients 11

Ruxolitinib combined with panobinostat showed reductions in spleen volume and JAK2 allelic burden at earlier time points than ruxolitinib alone 15, 16
Ruxolitinib plus azacitidine produced an 82% response rate with a median time to response of 1 month, and 27% of patients had improvement in bone marrow fibrosis grade 15, 16

Allogeneic HSCT remains the only potential cure for myelofibrosis and is recommended for transplant-eligible patients younger than 70 years with intermediate-2 or high-risk disease, and for patients younger than 65 years with intermediate-1 risk disease who have red cell transfusion dependence, >2% circulating blasts, or adverse cytogenetics 10, 11
Ruxolitinib is widely used for spleen shrinkage before HSCT, though optimal duration of JAK inhibitor therapy before transplantation remains unknown 10, 11