Virus-Specific T Cells (VSTs) Therapy for Progressive Multifocal Leukoencephalopathy (PML)- a Novel Therapy to Combat a Fatal Disease

Abstract

<h3>Introduction</h3> PML is a rare infection with JC virus affecting mostly oligodendrocytes and the white matter of the central nervous system. It affects patients with profound cellular immunodeficiency such as uncontrolled HIV or those receiving immunosuppression for neoplastic and autoimmune diseases. Prognosis is poor as there is no effective therapy except for immune recovery which is not feasible in all cases. Herein, we describe using Quadrivalent (CMV,EBV, Adenovirus and BK) VSTs in a recipient of an unrelated donor hematopoietic cell transplant (HCT) with PML. <h3>Methods</h3> A 64-year-old female with history of acute myeloid leukemia who underwent 10/10 HLA matched unrelated donor peripheral blood HCT complicated by acute mild skin graft vs host disease. She was off all immunosuppression by 7 months post transplant. At 15 months post HCT, she presented with mild confusion, left hemianopia and difficulty performing some routine tasks. Brain MRI showed demyelination involving the right parietal lobe, corpus callosum and bilateral dorsal periventricular areas. <i>Cerebrospinal fluid (</i>CSF) with JC virus DNA load of 389,773 copies/ml. Serum JC virus level was 1112 copies/ml and CD 4 218 (8.7%). Patient was referred to Cincinnati Children's Hospital for third-party VST infusion . A 3/10 HLA matched unit from their existing VST bank was infused 3 days after her PML diagnosis. She received a total of 6 VST infusions, each 28 days apart. <h3>Results</h3> Patient was monitored with monthly <i>C</i>SF JC virus and weekly serum JC virus levels. JC virus was cleared from serum and CSF after the fourth and fifth VST infusions, respectively (figure 1). T cell expansion analysis against BK was done by ELISpot (figure 2). Patient received a total of 6 VST infusions. Neuro symptoms stabilized after the second infusion. At 7.5 months from diagnosis (3 months since last VST infusion), she remained neurologically stable with no new deficits, GVHD or other toxicities. <h3>Conclusions</h3> VSTs with BK activity is a promising therapy for PML patients in whom immune reconstitution is unlikely to occur in a short time frame. More studies are warranted to evaluate the efficacy and long term outcomes of this method. Physicians should be aware of this novel therapy in selected PML cases given poor disease outcomes and lack of effective alternative therapies.