Painful splenomegaly can be treated temporarily with ruxolitinib, hydroxyurea, thalidomide, lenalidomide, cladribine, or radiation therapy, but sometimes requires splenectomy.[19,32] The decision to perform splenectomy represents a weighing of the benefits (i.e., reduction of symptoms, decreased portal hypertension, and less need for red blood cell transfusions lasting for 1 to 2 years) versus the debits (i.e., postoperative mortality of 10% and morbidity of 30% caused by infection, bleeding, or thrombosis; no benefit for thrombocytopenia; and accelerated progression to blast crisis that was seen by some investigators but not others).[4,32]
After splenectomy, many physicians use anticoagulation for 4 to 6 weeks to reduce portal vein thrombosis, and hydroxyurea can be utilized to reduce high platelet levels (>1 million). However, data from a retrospective review of 150 patients who underwent surgery provided documentation that 8% of the patients had a thromboembolism and 7% had a major hemorrhage with prior cytoreduction and postoperative subcutaneous heparin used in one-half of the patients.
Hydroxyurea is useful in patients with splenomegaly but may have a potential leukemogenic effect. In patients with thrombocytosis and hepatomegaly after splenectomy, cladribine has shown responses as an alternative to hydroxyurea. The use of interferon-alpha can result in hematologic responses, including reduction in spleen size in 30% to 50% of patients, though many patients do not tolerate this medication.[36,37] Favorable responses to thalidomide and lenalidomide have been reported in about 20% to 60% of patients.[17,18,19,38,39][Level of evidence: 3iiiDiv]
A response defined as 50% reduction of splenomegaly or development of transfusion independence was attained by one-third of 34 symptomatic patients using tipifarnib.[Level of evidence: 3iiiDiv] A more aggressive approach involves allogeneic peripheral stem cell or bone marrow transplantation when a suitable sibling donor is available.[41,42,43,44] Allogeneic stem cell transplantation is the only curative treatment available, but the morbidity and mortality limit its use to younger high-risk patients. Detection of the JAK2 mutation after transplantation is associated with a worse prognosis.
- Clinical trials involving other JAK2 inhibitors.
- Allogeneic peripheral stem cell or bone marrow transplantation.[42,43,44,46]
- Splenic radiation therapy or radiation to sites of symptomatic extramedullary hematopoiesis (e.g., large lymph nodes, cord compression).
Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with primary myelofibrosis. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.