Treatment of splenomegaly

Painful splenomegaly can be treated temporarily with ruxolitinib, hydroxyurea, thalidomide, lenalidomide, cladribine, or radiation therapy, but sometimes requires splenectomy.[29,50,61] 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 the blast-crisis phase that was seen by some investigators but not others).[7,50]

After splenectomy, many physicians use anticoagulation therapy for 4 to 6 weeks to reduce portal vein thrombosis. Hydroxyurea can be used to reduce high platelet levels (>1 million).[62] However, in a retrospective review of 150 patients who underwent surgery, 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.[63]

Hydroxyurea is useful in patients with splenomegaly but may have a leukemogenic effect.[7] In patients with thrombocytosis and hepatomegaly after splenectomy, cladribine may be an alternative to hydroxyurea.[52] The use of interferon alfa may result in hematological responses, including reduction in spleen size in 30% to 50% of patients, though many patients do not tolerate this medication.[53,54] Favorable responses to thalidomide and lenalidomide have been reported in about 20% to 60% of patients.[27-29,47-49][Level of evidence C3]

A more aggressive approach involves allogeneic peripheral stem cell or bone marrow transplant when a suitable donor is available.[41-46] Allogeneic stem cell transplant is the only potentially curative treatment available, but the associated morbidity and mortality limit its use to younger, high-risk patients.[44,64] Detection of a JAK2 variant after transplant is associated with a worse prognosis.[65]