The JAK1/2 inhibitor ruxolitinib is a potent immunomodulator and effectively treats myeloproliferative disease such as polycythemia vera (PV) and myelofibrosis (MF) by reducing spleen size and constitutional symptoms. For patients with PV and MF who have undergone liver transplantation, however, ruxolitinib could increase the risk of infectious complications due to long-term immunosuppression post-transplant.
In an article published in Clinical Case Reports, study authors shared details from two patients who developed progressive myeloproliferative disease after liver transplantation. Both patients had splenomegaly and constitutional symptoms and were therefore treated with ruxolitinib.
Patient 1, a 49-year-old woman who developed JAK2 V617F-positive PV after liver transplant had progressed to post-PV myelofibrosis three years after diagnosis. Fearing potential side effects, she initially refused therapy with ruxolitinib but eventually her health deterioriated and her spleen enlarged to 22 cm, at which point she agreed to start treatment with ruxolitinib 10 mg twice daily. Within six months, her general health rapidly improved, spleen size decreased to 17 cm, and platelet counts normalized. Eighteen months later, she developed leukocytosis and erythrocytosis, which were attributed to the hematologic malignancy rather than infection. Consequently, the dose of ruxolitinib was increased to 15 mg twice daily. Blood counts and general health improved immediately once more, so that ruxolitinib has been continued at the higher dose. Since then, the patient experienced five further episodes of cystitis, which rapidly responded to oral antibiotic treatment.
Patient 2 was a young female patient who underwent three liver transplantations because of recurrent thrombotic events, starting at age 19. Myeloproliferative disease was suspected but was not confirmed until at 35, when JAK2 V617F-positive polycythemia vera was confirmed by genetic testing and bone marrow biopsy. First, phlebotomies were used to lower high hematocrit, then ruxolitinib 15 mg twice daily was initiated. After she developed progressive pancytopenia, ruxolitinib dose was reduced to 10 mg once daily. The dosage was later reduced to two divided daily doses of 5 mg after the patients reduced hemoglobin and platelet counts stabilized and spleen size decreased. The lower doses further improved tolerability and the patient has not experienced any infectious complications during 19 months of follow-up.
“Taken together, our patients confirm a positive treatment response of myeloproliferative disease to ruxolitinib, leading to a rapid relief of symptoms and improved quality of life,” the authors commented. “We hope that our case series will stimulate more reports on the use of ruxolitinib in solid organ transplantation to establish optimal concomitant immunosuppression regimens and monitoring intervals.”