The Journey of Primary Myelofibrosis to Splenic Marginal Zone Lymphoma on the Wheels of Ruxolitinib

Excerpt

A 55 years old woman presented with massive splenomegaly (20 cm below costal margin). Base line hemogram revealed; Hb 136 g/L, WBC 9.9 × 10⁹/L, Platelets 208 × 10⁹/L, Neutrophil 45%, Lymphocyte 36%, Monocyte 05%, myelocytes 6%, metamyelocytes 4%, eosinophil 3% and 1% blasts. Peripheral smear revealed leucoerythroblastic picture with 6 nRBCs/100 WBC and tear drop cells. Bone marrow biopsy showed mild osteosclerosis, diffuse fibrosis with megakaryocytic hyperplasia and clustering. Reticulin stain showed grade 2–3 fibrosis and Masson’s trichrome showed few collagen bundles. JAK 2 V617F mutation by ASO-PCR was positive. In view of massive splenomegaly, she was initially treated with hydroxyurea for 3 months with reduction in spleen size to 14 cm below costal margin and then she was put on ruxolitinib. CBC at that time revealed: Hb 97 g/L, WBC 9.1 × 10⁹/L Platelet 162 × 10⁹/L Neutrophil 53% Lymphocyte 35%. On follow up she was noted to have progressive increase in lymphocyte count with increasing spleen size. After 6 months of ruxolitinib her WBC count increased to 16.7 × 10⁹/L with peripheral smear showing 74% small mature lymphocytes. Peripheral blood immunophenotyping revealed 55% B cells (CD 19+) which were bright CD 20 positive and lambda restricted while negative for CD5, CD10, CD23, CD200, CD 38, CD11c, CD 25, CD 103 and CD123 (Fig. 1). This immunophenotype was consistent with splenic marginal zone lymphoma. As patient was clinically asymptomatic, it was decided to stop ruxolitinib and observe lymphocyte count before starting treatment with rituximab. She was then put back on hydroxyurea which has led to gradual normalization of lymphocyte counts (Fig. 2). At present patient is clinically well, on hydroxyurea for myelofibrosis and hasn’t developed aggressive lymphoma 24 months after stopping ruxolitinib.

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