Effectiveness of lenalidomide in a patient with refractory anemia with ring sideroblasts and thrombocytosis with JAK2 (<scp>V</scp>617<scp>F</scp>) mutation
Authors: Ilaria Nichele, Marco Ruggeri, Francesco Rodeghiero
Journal: American Journal of Hematology (2015)

In their disease overview in the American Journal of Hematology 1, Patnaik and Tefferi pleaded for additional studies supporting the role of lenalidomide in the treatment of refractory anemia with ring sideroblasts and thrombocytosis (RARS-T). We describe here a patient with RARS-T and JAK2 V617F mutation, who reached transfusion independency and good control of platelet count after 4 years of treatment with lenalidomide, without relevant side effects. In September 2006, a 58-year-old man was admitted for anemia (hemoglobin 98 g/L) and thrombocytosis (1163 × 109/L). Physical examination revealed mild splenomegaly and hepatomegaly. Peripheral blood examination showed platelet anisocytosis, normal red blood cell morphology, and a normal differential leukocyte count. Erythropoietin and iron level were within normal range; serum lactate dehydrogenase was increased (590 U/L; normal range 200–420 U/L). Bone marrow aspirate was characterized by increased cellularity, with erythroid hyperplasia and marked dyserythropoiesis. Prussian blue iron stain showed 30% of ring sideroblasts. Megakaryocytes were also greatly increased with atypical features (large hyperlobulated nuclei). Granulocytic series, lymphocytes, and plasma cells were normal. No blast cells were observed. Bone marrow biopsy confirmed the increased erythropoiesis and the presence of variable size megakaryocytes with large hyperlobulated nuclei. Reticulin was not increased (MF = 0 on Bauermeister scale) and CD34-positive cells were <1% of total cellularity. Ring sideroblasts were confirmed. Cytogenetic analysis showed normal karyotype and FISH examination was negative; allele-specific PCR method revealed the presence of JAK-2 V617 mutation. Accordingly, RARS-T with JAK-2 mutation was diagnosed. On October 2007, hydroxycarbamide was started at 500 mg daily to control the increasing platelet count (1340 × 109/L). After 4 months of therapy, steroids were started due to a mild decrease of hemoglobin (from 96 g/L to 83 g/L), without efficacy. Subcutaneous recombinant EPO at 40.000 units weekly yielded no hemoglobin increase after 4 weeks and this treatment was also stopped. The patient became transfusion-dependent requiring 2 red blood cells units monthly. On November 2010, hydroxycarbamide was stopped and repeated courses of lenamidomide were initiated at 10 mg daily for 21 consecutive days every 28 days, on the basis of the report of its efficacy in two similar cases 2. This therapy has been administered for the last 4 years and the patient is still on treatment. Transfusion independence was reached at the end of the first cycle and persists with hemoglobin level always above 90 g/L and platelet level stabilized below 600 × 109/L (Fig. 1). Neither hematological toxicity nor other adverse events have been recorded until now. A bone marrow aspirate performed after 3 years of treatment showed the persistence of dyserythropoiesis and of ring sideroblasts. Platelet count and hemoglobin level are represented on the y-axis as a function of time. Patient received lenalidomide from November 2010. The low hemoglobin level and high platelet count improved progressively and stabilized to acceptable values after starting lenalidomide treatment, compared to values while the patient was on hydroxycarbamide (since October 2007). No red blood cells transfusions were required. This case confirms that the low-dose, single-agent lenalidomide could be effective in patients with a diagnosis of RARS-T and JAK2 V617F mutation, after failure of EPO and cytoreduction, leading to transfusion independence and good platelet count control, with a favorable safety profile. Ilaria Nichele1*, Marco Ruggeri1, Francesco Rodeghiero1 1Department of Hematology, San Bortolo Hospital, Vicenza, Italy