Renal impairment and lack of efficacy: case reportA 4.5-month-old boy exhibited lack of efficacy during treatment with fludarabine, busulfan, thiotepa, ciclosporin, methotrexate and antithymocyte globulin for graft versus host disease prophylaxis. Additionally, he developed renal impairment during treatment with ciclosporin [routes not stated].The boy with a confirmed globoid cell leukodystrophy and a past medical history of left renal agenesis, was admitted to a hospital in Poland for high-dose chemotherapy with subsequent allo-haematopoietic stem cell transplantation (HSCT). He was born at gestational age 39 weeks with an Apgar score of 7/8/9 in 1/3/5 minute, and with a birth weight of 4.3kg. After birth, right Erb-Duchenne palsy and kidney agenesis were diagnosed. His family history was significant for late-infantile Krabbe disease (KD). Due to family history, genetic counselling was performed, and he was diagnosed with late-infantile KD. The postnatal period was found to be uneventful, including his neuropsychological development. He received conditioning regimen for the prevention of graft rejection and as a graft versus host disease prophylaxis, which included: fludarabine 30 mg/m2, busulfan 4 × 4 × 1 mg/kg, thiotepa 2 × 5 mg/kg, ciclosporin [cyclosporin A] from day -1, methotrexate 10 mg/m2 on days +1, +3, +6 and antithymocyte globulin [Grafalon] 3 × 10 mg/kg on days -3, -2, -1. In the post-transplant period hepatomegaly, elevation of bilirubin and weight gain required implementation of furosemide, with transfusion-refractory thrombocytopenia and peripheral oedema were also observed.The boy received vitamin K, transfusions of plasma and cryoprecipitate. Spironolactone, ursodeoxycholic acid and fluid restrictions were also given. He was also diagnosed with veno-occlusive disease on day +19. Therefore, defibrotide was initiated from day +20 to day +34. A rise in urea and creatinine levels from the baseline value were also observed. An impairment in his renal function was noted and considered to be related to the nephrotoxic effect of ciclosporin [duration of treatment to reaction onset not stated]. Furthermore, diuresis was monitored, and a restriction in amino acid intake was recommended with the insertion of urinary catheter. Taking into account the agenesis of the kidney, ciclosporin was withdrawn, and he was initiated on unspecified steroids and mycophenolate mofetil. On day +35, grade I acute graft versus host disease (aGvHD) of the skin was occurred with typical manifestations on the trunk and head.The boy was again restarted on unspecified steroids and ciclosporin with success. Due to proper treatment a gradual improvement in renal and liver parameters were also observed with a reduction in the abdominal circumference and peripheral oedema. He was discharged on day +61 without any significant adverse events and with full donor chimerism. Normal activity of blood lysosomal enzymes was confirmed at 18 months post-transplant. He remained alive and well 5 years post-transplant without any significant late...
