A Case Series on Post Essential Thrombocytosis Myelofibrosis Conversion to Chronic Myeloid Leukemia
Authors: Cherian Silvia , Taylor Christie , Boban Abijha , Johnson Andrew , Hunter Anthony M. 
Published: December 2024

The progression of myeloproliferative neoplasms (MPNs) presents a complex and multifaceted challenge in hematologic oncology. Essential thrombocythemia (ET) is one such MPN that can evolve into more aggressive forms, including myelofibrosis (MF) and, in rare cases, chronic myeloid leukemia (CML). This abstract discusses three distinct cases of elderly patients initially diagnosed with ET, who subsequently developed CML.
Case 1 depicts a 74-year-old male with a history of Stage IIc adenocarcinoma of the prostate, post radical prostatectomy, papillary renal cell carcinoma, post right nephrectomy, recurrent VTE, and anemia who was diagnosed with JAK2 V617F mutation ET. Initial bone marrow biopsy showed hypercellular bone marrow with megakaryotic hyperplasia and reticulin fibrosis. After observation of the patient for 3 years, he was found to have splenomegaly on CT when he presented with abdominal pain and myalgia to the ED. WBC trended up from 18,000 to 109,000 cells/μL within 2 months, along with LDH (1021 U/L), uric acid (7.1 mg/dL), platelets (607,000 per μL). Repeat bone marrow biopsy showed CML and FISH was positive for the 9:22 BCR/ABL translocation. He was started on dasatinib, ruxolitinib, and hydroxyurea.
Case 2 depicts a 71-year-old female with a history of breast DCIS status post surgical excision, radiation therapy and tamoxifen, hypertension, glaucoma, and idiopathic atrial tachycardia who was diagnosed with JAK2 V617F mutation ET after discovering elevated platelet counts (584,000 per μL) and splenomegaly on CT. Initial bone marrow showed hypercellular marrow, and she was treated with Aspirin (81mg daily). Ten years later, she presented with extreme fatigue, thirty-pound weight loss, early satiety and dyspnea on exertion. Labs showed elevated WBC (141,000 cells/μL), platelets (557,000 per μL), and LDL (953 U/L). Peripheral blood smear showed myeloblasts and basophilia. Repeat bone marrow biopsy revealed CML with t(9;22). The patient was started on nilotinib 300 mg twice daily and had complete remission within 6 months. Due to severe fibrosis noted on another bone marrow biopsy, she was started on Ruxolitinib and later paired with a clinical trial of bromodomain and extra-terminal (BET) inhibitor.
Case 3 depicts a 60-year-old male with a history of diabetes, chronic kidney disease, and benign prostatic hyperplasia who was diagnosed with ET after his platelet count was found to be roughly 1 million. He was initially treated with anagrelide and hydroxyurea. On further workup, JAK2 V617F mutation was detected. Fifteen years later, evaluation of progressive leukocytosis and anemia with bone marrow biopsy revealed post-ET myelofibrosis. His medications were changed to darbepoetin and ruxolitinib. After ten years, the patient had an abrupt increase in his WBC from 20.0 to 78.9. BCR-ABL PCR was positive and was started on Imatinib for treatment of CML.
The transformation from ET to CML, as observed in our cases, highlights a rare but critical pathway in the natural history of MPNs. The commonality of the JAK2 V617F mutation among these patients suggests a potential underlying mechanism that predisposes to such transformations. The presence of this mutation has been well-documented in various MPNs, but its role in the transition from ET to CML requires further elucidation. Early intervention to diagnose and treat ET, followed by prevention of myelofibrosis may need to be investigated to decelerate the progression to CML.