Successful Management of Progressive Multifocal Leukoencephalopathy Post TCR Alphabeta/CD19 Depleted Haploidentical Stem Cell Transplant

Introduction- Progressive multifocal leukoencephalopathy (PML) caused by JC virus is a rare but mostly fatal viral disease of brain affecting immunosuppressed patients. Here we describe successful management of JC virus induced PML in a young man post TCR alphabeta/CD19 depleted haploidentical hematopetic stem cell transplant (HSCT). Methods-A 22-year old, male with thalassemia major underwent TCR alpha-beta/CD19 depleted haploidentical HSCT in March 2014 from his 5/10 matched brother as donor. Intensive chelation and hydroxyurea were administered for 6-months before HSCT. The conditioning was with thiotepa 10 mg/kg, fludarabine 150 mg/m2, cyclophosphamide 29 mg/kg and Rabbit ATG (thymoglobulin) 4.5 mg/kg. Peripheral blood stem cells (16 million/kg CD34+ cells) were harvested and infused after TCR alpha-beta/CD19 depletion. He had primary graft rejection but had autologous recovery by day+40. He underwent a second TCR alphabeta/CD19 depleted haploidentical HSCT 6-months later from his father as donor (5/10 matched). He underwent splenectomy 3-months prior to 2^nd HSCT. As anti-HLA antibodies were present so he was treated with rituximab, plasmapheresis and bortezomib over 4 weeks which was followed by conditioning with alemtuzumab-1mg/kg, fludarabine 150mg/m2, treosulfan 42g/m2 and thiotepa 8 mg/kg. Peripheral blood stem cells (9 million/kg) were infused after TCR alphabeta/CD19 depletion. Neutrophils engrafted on day+11 and platelets on day+13.He developed grade I skin graft vs. host disease (GVHD) which was treated with sirolimus. It was changed to tacrolimus on day+180 for chronic skin GVHD and dryness of eyes.Chimerism on day+30, 100 and 1-year was fully donor. At 1-year his lymphocyte counts showed CD4-157/ul, CD8-368/ul, CD19-1055/ul and CD16/56-600/ul. Results- One-year post HSCT, he was re-admitted with right sided complex partial seizure. He was on tacrolimus, amlodipine and co-trimoxazole. He had severe headache. He was fully conscious, oriented and had no neurological deficits. Over next few days he developed aggressive behavior, hallucinations and short term memory loss. CT head showed left parieto-occipetal region edema. MRI brain with contrast and spectroscopy showed non-contrast enhancing white matter changes in the region corresponding to CT scan. CSF showed no cells and protein & sugar were normal. However CSF was positive by PCR for JC virus confirming the diagnosis of PML.Quantitative PCR in CSF showed 21000 copies/ml of JC virus. Tacrolimus was stopped. He was then started on intravenous cidofovir with oral probenicid as per protocol. Cidofovir 5mg/kg loading dose followed by 3 mg/kg once a week for 8 weeks. JC virus copies reduced to 1200/ml in CSF after 3 weeks and became negative after 5 weeks. Tablet risperidone (2 mg orally twice daily) was given to block serotonin receptor mediated uptake of virus in oligodendrocytes for 2 months. Tablet mefloquine was also given for its antiviral effect in JC virus-5mg/kg daily for 3 days followed by once weekly for 6 months. His condition improved and was discharged a month later. He is very well now more than 3-years after JC virus infection.He has no neurological deficits and memory is normal. He is off all medications and has no GVHD. Conclusion - JC virus induced PML post HSCT can possibly be managed by removing immune suppression adding risperidone and giving antiviral cidofovir and mefloquine.