1 Pediatric Nephrology Unit, Pediatrics Department, Hospital de Dona Estefânia, Centro Hospital Universitário de Lisboa Central, EPE, Lisboa, Portugal.
2 Hematopoietic Cell Transplantation Unit, Haematology Department, Instituto Português de Oncologia Francisco Gentil, Lisboa, Portugal.
3 Pediatric Unit, Children and Adolescents Oncology Department, Instituto Português de Oncologia Francisco Gentil, Lisboa, Portugal.
- Port J Nephrol Hypert 2019; 33(1): 61-67 • Advance Access publication 27 March 2019
Resumo: Ifosfamide is an antineoplastic drug widely used in the treatment of paediatric malignancies. However, in up to 50% of patients, it is associated with nephrotoxicity ranging from asymptomatic tubulopathy to overt renal failure. A two-year-old Caucasian boy was diagnosed with stage IV Burkitt lymphoma, with hepatic and renal and bone marrow involvement. Baseline evaluation showed GFR of 60 mL/min/1.73 m2. He started chemotherapy with LMB 96 protocol group B with 5 courses of chemotherapy with vincristine, cyclophosphamide, doxorubicin, prednisone, and intrathecal administration of cytarabine and methotrexate. After the first chemo protocol, the patient was in remission and recovered normal renal function, but three months later he relapsed with involvement of the liver and kidneys. The patient initiated a salvage regimen with R-ICE (rituximab – ifosfamide, carboplatin, etoposide) intrathecal methotrexate and cytarabine and allogeneic stem cell transplantation was proposed. After achieving complete remission, he underwent allogeneic stem cell transplantation with busulfan and cyclophosphamide. Graft versus host disease prophylaxis was made with tacrolimus and methotrexate and infection prophylaxis with fluconazole and acyclovir.
However, during treatment of the relapse, the patient presented downward crossing of weight and height centiles without recovery after treatment terminus and, following transplantation, consecutive laboratory testing suggested tubulopathy. Upon nephrologist referral, he was diagnosed with Fanconi syndrome and adequate supplementation was initiated with improvement of the patient’s general condition and slow centile catch up. After literature review, the most probable causing agent was determined to be ifosfamide, as the nephrotoxic effects of the other medications prescribed tend to be reversible after stopping. Nephrotoxicity secondary to chemotherapy is a major cause of morbidity in paediatric cancer survivors. Our case represents a rare situation with unspecific clinical signs. Clinicians must be alert to the necessity of close monitoring to identify renal toxicity, mainly tubular dysfunction, as early as possible and allow adequate supplementation, which is crucial in preventing side effects.
Palavras-chave: Ifosfamide, Nephrotoxicity, Fanconi Syndrome