RESUMEN
Strategies effective for accelerating methotrexate removal in delayed methotrexate excretion have not been universally accepted. The authors report a case of a 12-year-old girl with osteosarcoma who developed acute renal failure immediately after the first administration of high-dose methotrexate. Plasma methotrexate was effectively removed with repeated charcoal hemoperfusion in addition to plasma exchange and leucovorin rescue. Charcoal hemoperfusion was most effective for reducing plasma methotrexate with approximately 50% of methotrexate being reduced during each of the procedures. No rebound increase in MTX levels was observed. The patient received further therapy with other cancer drugs and has been well for 3.5 years.
Asunto(s)
Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/terapia , Antimetabolitos Antineoplásicos/efectos adversos , Hemoperfusión , Metotrexato/efectos adversos , Antimetabolitos Antineoplásicos/administración & dosificación , Neoplasias Óseas/sangre , Neoplasias Óseas/tratamiento farmacológico , Carbón Orgánico , Niño , Femenino , Humanos , Metotrexato/administración & dosificación , Osteosarcoma/sangre , Osteosarcoma/tratamiento farmacológico , Radio (Anatomía)Asunto(s)
Leucemia Mielomonocítica Juvenil/genética , Leucemia Mielomonocítica Juvenil/patología , Mutación/genética , Proteínas ras/genética , Antineoplásicos/uso terapéutico , Preescolar , Estudios de Seguimiento , Humanos , Leucemia Mielomonocítica Juvenil/tratamiento farmacológico , Leucemia Mielomonocítica Juvenil/enzimología , Masculino , Proteínas ras/metabolismoRESUMEN
We present a patient with Bernard-Soulier syndrome harboring a novel mutation. Flow cytometric analysis showed that the glycoprotein (GP) Ib/IX complex was absent from the platelet surface. By immunoblotting, GPIbalpha, GPIbbeta and GPIX were not detected in the platelet lysates. Glycocalicin, the soluble GPIbalpha fragment, was also absent in the plasma. Genetic analysis revealed a novel homozygous 8-base pair deletion in the GPIbalpha gene, 1136_1143delTTCACATG, which was predicted to cause a frame shift and the addition of 13 altered amino acids followed by premature termination. No mutation was found in the coding sequence of the GPIbbeta or GPIX genes. We demonstrated that the novel deletion mutation resulted in complete defectiveness of the GPIbalpha protein and null expression of the entire GPIb/IX complex, and was responsible for the Bernard-Soulier syndrome phenotype in this patient. Although the presence of a truncated GPIbalpha protein has been often documented, complete absence of the protein has been scarcely reported in Bernard-Soulier syndrome patients with a GPIbalpha mutation causing a premature stop codon. An underlying molecular mechanism to explain how the synthesis of a truncated protein is inhibited in selected cases remains to be elucidated.