K KABLE1, S SO1, J LI1, L CLANCY2,3, N ROGERS1,2, E BLYTH2,3,4, B GETTA4, G WONG1,2, P O’CONNELL1, 2, J CHAPMAN 1, 2, D GOTTLIEB2,3,4
1Department of Nephrology, Westmead Hospital, Westmead, New South Wales; 2The Westmead Institute for Medical Research, Australia; 3Sydney Cell and Gene Therapy Laboratory, Westmead Hospital; 4Blood and Marrow Transplant Unit, Australia
Background: Human cytomegalovirus (CMV) infection in transplant patients can lead to devastating invasive disease. Ganciclovir and foscarnet resistance poses a therapeutic dilemma. Adoptively-transferred CMV T-cells have been used in bone marrow transplants, but there has been reluctance to adopt this in solid-organ transplants given the theoretical risks of graft sensitisation and rejection.
Case Report: A 43 year old lady with type 1 diabetes and end stage renal failure received a simultaneous kidney-pancreas transplant in March 2015. She received standard induction therapy, but two weeks post-transplant, she received methylprednisolone and anti-thymocyte globulin for acute rejection. Mycophenolate was subsequently changed to azathioprine for gastrointestinal intolerance.
She received 12 months prophylaxis with valganciclovir as she was the CMV-seronegative recipient of a CMV-seropositive graft. She developed CMV disease three months post cessation and was restarted with treatment dose valganciclovir with improvement in the viral copy number. Six months later, she developed breakthrough invasive CMV disease and her viral CMV copies continued to rise to 800,000 copies/mL despite reduction in immunosuppression and treatment with IV foscarnet.
Gene mutation testing revealed UL 97 and UL 54 mutations, confirming foscarnet resistance. Novel therapies including maribavir, brincidofovir and letermovir were unavailable. She received a trial of primed IV CMV T-cell therapy in March 2017, and achieved excellent response. Her current CMV copies now below 1000 copies/ml. She has maintained stable graft function with no clinical evidence of rejection.
Conclusions: T-cell therapy may be effective against invasive, resistant cytomegalovirus disease in transplant recipients, without incurring adverse effects including acute rejection and graft loss.