Cózar Olmo J A, Martínez Colmenero C, Peláez Pleguezuelos I, Leiva Gea I, López García A B, de la Cruz Moreno J
Unidad Gestión Clínica de Pediatría, Unidad Oncohematología, Complejo Hospitalario de Jaén, Jaén, España.
An Pediatr (Barc). 2009 Sep;71(3):230-4. doi: 10.1016/j.anpedi.2009.05.014. Epub 2009 Jul 18.
Methotrexate (MTX) is widely used as anticancer agent in various malignancies, including acute lymphoblastic leukaemia, lymphoma and osteosarcoma. High doses of MTX may cause acute renal dysfunction. Nephrotoxicity is prevented by the use of alkalinization and hydration. More recently Carboxypeptidase-G2, a recombinant bacterial enzyme that rapidly hydrolyzes MTX to inactive metabolites, has become available for the treatment of acute nephrotoxicity. On the other hand, glutamine is usually administered in oncology treatments to avoid other side effects. We report a case of an adolescent who was diagnosed with T lymphoblastic lymphoma. He was receiving treatment with glutamine when the third course of methotrexate was administered (5 g/m(2)) and he suffered a deterioration in his renal function. Carboxypeptidase was used but the methotrexate serum concentration reduction was not satisfactory. The technique to assess the amount of enzyme-inactivated methotrexate by quantification of MTX metabolites is not available in our country, therefore, the concentrations of MTX may be overestimated. The literature was reviewed to study the influence of glutamine on delayed methotrexate elimination which may lead to acute toxicity.
甲氨蝶呤(MTX)作为抗癌药物被广泛应用于各种恶性肿瘤,包括急性淋巴细胞白血病、淋巴瘤和骨肉瘤。高剂量的MTX可能会导致急性肾功能障碍。通过碱化和水化可预防肾毒性。最近,羧肽酶G2,一种能迅速将MTX水解为无活性代谢产物的重组细菌酶,已可用于治疗急性肾毒性。另一方面,在肿瘤治疗中通常会使用谷氨酰胺以避免其他副作用。我们报告一例被诊断为T淋巴母细胞淋巴瘤的青少年病例。在给予第三疗程甲氨蝶呤(5 g/m²)时,他正在接受谷氨酰胺治疗,随后出现肾功能恶化。使用了羧肽酶,但甲氨蝶呤血清浓度降低并不理想。我国尚无通过定量MTX代谢产物来评估酶灭活甲氨蝶呤量的技术,因此,MTX的浓度可能被高估。我们查阅了文献以研究谷氨酰胺对甲氨蝶呤延迟消除的影响,这可能导致急性毒性。