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An event is serious (based on the ICH definition) when the patient outcome is:
* death
* life-threatening
* hospitalisation
* disability
* congenital anomaly
* other medically important event
A 16-year-old girl developed BK virus infection, Klebsiella infection, cytomegalovirus (CMV) reactivation and Coronavirus disease 2019 (COVID-19) infection during immunosuppressant therapy with antithymocyte globulin, azathioprine, ciclosporin, cyclophosphamide, fludarabine, methotrexate and methylprednisolone. Additionally, she received immunosuppressant therapy with tacrolimus which contributed in development of COVID-19.
The girl, who had β-thalassemia major, was scheduled for haemopoietic stem cell transplantation (HSCT). In the pre-transplant evaluation, she received hydroxycarbamide [hydroxyurea], intensive chelation therapy and hypertransfusion for 45 days prior to transplant. Additionally, she received immunosuppressant therapy with fludarabine 30 mg/m 2/day and azathioprine 3 mg/kg/day [routes not stated]. Her medical history was significant for diabetes mellitus and CMV infection. She was hospitalised. In November 2019, she underwent HSCT. She received immunosuppressant therapy with antithymocyte globulin [anti-thymocyte globuline] 10 mg/kg/day, methylprednisolone [metilprednisolone] 1 mg/kg/day, ciclosporin [cyclosporine] 3 mg/kg/day, short term methotrexate 10 mg/m 2/day and post transplant cyclophosphamide 10 mg/kg/day [routes not stated]. On day +5, she developed febrile neutropenia secondary to Klebsiella spp sepsis. On day +8, she developed painful hepatomegaly and thrombocytopenia. She was diagnosed with venoocclusive disease.
The girl was treated with defibrotide. On day +22, she was diagnosed with osteonecrosis in both ankle bones [aetiology not stated]. On day +30, she developed dysuria and haematuria and tested positive for human BK virus. After 1 week, she developed CMV reactivation. She was treated with cidofovir. Subsequently, she developed itchy common erythema on the skin and was diagnosed with graft versus host disease on day +40. She was treated with methylprednisolone 2 mg/kg/day with partial improvement. After various treatments, she was discharged on day +52. On day +61, she had frequent watery defecation. Investigations revealed gastrointestinal graft versus host disease. She was treated with extracorporeal photopheresis. Ciclosporin was discontinued and she was initiated on tacrolimus [route and dosage not stated] and short term methylprednisolone. Three months after HSCT, she was diagnosed with bronchiolitis obliterans [aetiology not stated] and was treated with azithromycin, montelukast and unspecified steroids. Her chimerism results at the first, second, third and sixth months were 100%. In April 2020 (six months following HSCT), she presented with fever, cough, muscle pain and weakness. She was hospitalised. Thorax CT showed widespread infiltrations. A SARS-CoV-2 test of the nasopharyngeal swab showed positivity for COVID-19. Her BK virus infection, Klebsiella infection, CMV reactivation and COVID-19 infection were attributed to immunosuppressant therapy with antithymocyte globulin, azathioprine, ciclosporin, cyclophosphamide, fludarabaine, methotrexate and methylprednisolone. Additionally, COVID-19 infection was attributed to tacrolimus therapy [duration of treatments to reaction onsets not clearly stated]. She started receiving off label treatment with hydroxychloroquine at a dose of 13 mg/kg/day on day 1 followed by 6.5 mg/kg/day for subsequent 4 days and lopinavir/ritonavir 300−75 mg/kg/day [routes not stated]. Subsequently, her fever and respiratory findings began to improve. On day 5 and day 10 following treatment initiation, PCR test showed negative findings for SARS-CoV-2. Eventually, her complaints decreased and imaging and laboratory finding returned to normal. Thereafter, she was discharged.