You Make the Call: Is JAK2 positivity clinically significant in this 28-year-old patient with Budd-Chiari syndrome?

Peter Emanuel, MD
Director of Oncology Services, CHI St. Vincent, a component of CommonSpirit Health, Little Rock, Arkansas

This month, Peter Emanuel, MD, discusses the clinical significance of JAK2 positivity in a patient with Budd-Chiari syndrome.

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I was called for an opinion regarding the management of a 28-year-old man who has a history of Budd-Chiari syndrome in 2015. He did not have any other significant past medical history. However, on review of his chart, I found that PCR testing of the peripheral blood came back positive for JAK2 V617F in August of 2020. The variant allele frequency was 0.06%. Is there a quantitative cutoff for which the allele burden is considered clinically significant? Should I attribute his hepatic vein thrombosis to the JAK2 positivity?


I am unaware of any particular cutoff or lower limit threshold for considering allele burden to be considered clinically significant or insignificant. As far as I am aware, positive is positive. If it has not already been accomplished, I would undertake a very thorough investigation to determine if there is another reason for this young man to have developed Budd-Chiari syndrome. If you exclude all other causes, then I would attribute his hepatic vein thrombosis to his JAK2 positivity.

Many years ago I had a somewhat similar case. A young woman in her early 20s presented with very severe Budd-Chiari syndrome and no clear attributable cause. She was found to be JAK2 positive, but that was long before we were able to test for percentage of allele burden. Her diagnosis was therefore an unclassifiable myeloproliferative neoplasm. Over some years she developed collateral venous circulation and her hepatic problems lessened. Then, some 8 to 10 years after initial presentation, she informed me that she and her husband desired a baby. Despite significant preparations, at the time of delivery she again developed new thromboses and recurrent liver engorgement with dysfunction. Fortunately, over time, things again calmed down. She has a healthy youngster, but that was her last pregnancy attempt.

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I am treating a 61-year-old female diagnosed with Philadelphia chromosome-positive acute lymphocytic leukemia who has multiple comorbidities, including severe diabetes and obesity (body mass index of 43), who is not a candidate for allogeneic hematopoietic cell transplantation. She was initially treated with a single cycle of rituximab, hyper-CVAD (cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone), and dasatinib. She achieved a complete remission, but had a difficult induction course and was then switched to dasatinib, prednisone, and vincristine. A bone marrow biopsy continues to show morphologic and immunologic remission, but is still positive for BCR-ABL transcripts at a low level. Should I continue maintenance as before, switch to a different tyrosine kinase inhibitor, or try other immune treatments such as blinatumomab?

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