Splenic Infarction in a Patient with Spent-Phase Polycythemia Rubra Vera (PRV) Treated with Lenalidomide.

Introduction: Lenalidomide (LD) is an oral thalidomide analog with both immunomodulatory and anti-angiogenic properties. It is approved for use in myelodysplastic syndromes (MDS), specifically low-risk and intermediate 1 with 5Q-. LD has also been approved for relapsed multiple myeloma (MM). A major complication associated with LD includes venous thromboembolism (VTE), especially in combination with steroid and erythropoetin (EPO). VTE occurs in 2% of MDS, but range from 6.6% as monotherapy in MM to 8.5%–13.5% when combined with dexamethasone. Zonder reports a preliminary incidence of 75% (9/12 patients) in the SWOG 0302 trial of LD and dexamethasone in previously untreated myeloma. With the addition of ASA in these patients the incidence dropped to 19%. Patients with polycythemia rubra vera (PRV) have a higher incidence of VTE (5.1%> age 70). JAK-2 mutation (tyrosine kinase mutation) occurs as a sporadic event in 75% of patients with PRV and is associated with an older age group, inferior survival, myelofibrosis, acute leukemia and thromboembolic events. Recent studies with LD in this group of PRV and spent-phase myelofibrosis have shown encouraging results. LD has an activity of 46% in myelofibosis by decreasing transfusions and splenomegaly. It would seem to have activity in spent-phase PRV. We report a seminal event of splenic infarction in a patient with PRV and myelofibrosis treated with LD.

Case Presentation: A 73 y/o male was diagnosed with PRV 16 yrs earlier. He underwent phlebotomy and received ASA. With a hyperproliferative phase he received hydrea as he was intolerant of IFN-A and anagrelide. Three months earlier, he developed fever, sweats, splenomegaly, and became transfusion dependent. His marrow confirmed myelofibrosis with dysplastic features. LD was begun at 25 mg daily. Three weeks later he developed pneumonia with bronchospasm and required hospitalization for antibiotics and steroids. He improved but returned 4 days later with left upper quadrant pain with CT findings consistent with multiple splenic infarcts. Prednisone was stopped and enoxaparin resulted in marked improvement. Currently, he has marked diminution in the size of his spleen from 13 cm to 4 cm. Currently, he is transfusion independent with marked clinical improvement.

Discussion: This report points several dynamic issues within the field of myeloproliferative syndromes. The JAK-2 mutation offers fertile areas of research within MPD disorders as a causative or sporadic mutation and as an associated with several adverse events including VTE and myelofibrosis. We report here a unique occurrence of VTE in the form of multiple splenic infarctions within the context of treatment of the spent-phase of PVR with JAK-2 mutation receiving LD. VTE events associated with LD are associated with DVT or pulmonary embolus and have not been associated with splenic infarction. Splenic infarction has also been reported in myelofibrosis. As further studies confirm efficacy with myelofibrosis it should be suggested that prophylaxis with warfarin or enoxaparin, especially in JAK-2 mutation patients, be considered. Physicians should be encouraged to report their experience in patients with MPD and lenalidomide.