Management of BK Polyomavirus in a Kidney Transplant Recipient With Primary Myelofibrosis on JAK-2 Inhibition - A...

The use of Janus Kinase (JAK) inhibitors with concomitant maintenance immunosuppressive therapy (IST) for the solid organ transplant (SOT) population presents significant challenges due to intensified immunosuppression resulting in an increased risk of opportunistic infections and malignancies coupled with limited clinical experience among transplant providers. A 48-year-old man presented with end-stage kidney disease secondary to IgA nephropathy requiring commencement of haemodialysis. He had a concurrent diagnosis of primary myelofibrosis (PMF), which did not require treatment at presentation. A year later, he underwent a living-donor kidney transplant from an HLA-identical sibling. The patient received induction IST with basiliximab and methylprednisolone, followed by standard maintenance therapy with tacrolimus and mycophenolate mofetil. The latter was reduced in dose due to underlying PMF. In the months following transplantation, he experienced worsening PMF parameters and was commenced on the JAK2 inhibitor, ruxolitinib. This was complicated by development of detectable BK Polyomavirus DNA (BKPyV-DNAemia), prompting adjustment of his immunosuppression regimen and dose reduction of ruloxlitinib. His course was further complicated by renal allograft rejection. Ruxolitinib was subsequently discontinued, and he transitioned to the second-generation JAK inhibitor fedratinib, which led to improvement in PMF parameters and stabilization of both graft function and BKPyV-DNAemia. This case highlights the therapeutic challenges inherent in integrating JAK inhibitors into established immunosuppression regimens in solid organ transplantation. It underscores the difficult balance between preserving graft tolerance and mitigating the risk of opportunistic infections such as BKPyV-DNAemia, while emphasising the need for close monitoring of net immunosuppression in this setting.