大剂量甲氨蝶呤治疗成人急性淋巴细胞白血病后浓度监测的临床研究

目的通过对急性淋巴细胞白血病（ALL）患者大剂量甲氨蝶呤（HD MTX）化疗后的血药浓度监测,分析MTX体内蓄积的影响因素、MTX蓄积者的临床表现,为MTX在临床上合理应用提供参考。方法通过对ALL患者HD MTX化疗后的血药浓度监测,分析MTX体内蓄积的影响因素、MTX蓄积者的临床表现,为MTX在临床上合理应用提供参考。结果①用药后0、20及44 h患者体内MTX浓度分别为（58.63±37.23,95%CI：41.20～76.05）μmol/L、（5.14±2.25,95%CI：0.44～9.84）μmol/L及（0.35±0.11,95%CI：0.013～0.57）μmol/L。②6例次患者出现MTX体内蓄积,蓄积组化疗前血肌酐水平明显高于非蓄积组分别为（68.81±6.48）和（50.4±10.6）μmol/L,P〈0.01];血肌酐水平与44 h的MTX浓度呈正相关（r=0.5739,P〈0.01）。③MTX蓄积组患者黏膜损害的发生率较非蓄积组明显增高（P〈0.05）。MTX蓄积的6例次患者中,5例次通过水化、碱化、增加CF的解救量,使MTX得以排泄,其中1例次出现MTX持续蓄积并伴发急性肾功能衰竭,在给予血液透析后,血MTX水平降至安全浓度以下。结论肾功能是影响MTX体内代谢的重要因素;当出现MTX体内蓄积时,可通过水化、碱化、加大CF的解救量促进其排泄,必要时可行血液透析等替代治疗。

Clinical study of monitering the methotrexate concentration of adult acute lymphoblastic leukemia patients treated with high-dose methotrexate

Objective To moniter the concentration of methotrexate in blood of acute lymphoblastic leukemia（ALL） patients treated with high dose methotrexate（HD MTX）,to analyze the factors affecting the accumulation of MTX,the effect of MTX on clinical manifestation of the patients,and apply it adequately in clinical settings.Methods Nineteen adult ALL patients received 20 courses of HD MTX（3 g/m2） were rescued with calcium folinate（CF） 24 h after the treatment.Blood concentration of MTX was detected 0h,20h and 44 h after the administration.To analyze the factors affecting the metabolism of MTX,related laboratory data were recorded before chemotherapy.Results 1.Blood concentration of MTX in 0h,20h and 44h after the administration was（58.63±37.23,95%CI： 41.20-76.05）μmol/L,（5.14±2.25,95%CI： 0.44-9.84） μmol/L and（0.35±0.11,95%CI： 0.013-0.57）μmol/L,respectively.2.Accumulation of MTX was observed in 6 cases which were characterized by higher level of serum creatinine before treatment （68.81±6.48） and（50.4±10.6）μmol/L,P＆lt;0.01].Serum creatinine was positively associated with the concentration of MTX in 44h（r=0.5739,P＆lt;0.01）.3.The incidence of mucos damage was significantly elevated in MTX accumulation group（P＆lt;0.05）.Elimination of MTX happened in 5 cases after hydration,basification and augmentation the dosage of CF.Moreover,there was one patient accompanied with successional accumulation and acute kidney failure.Hemodialysis was done to ensure the decreased concentration of MTX beneath the safe standard.Conclusion Renal function is an important factor affecting the metabolism of MTX.As to the occurrence of MTX accumulation,hydration,basification and increasing the dosage of CF were essential.If necessary,hemodialysis needs to be done.