Farrow A C, Buchanan G R, Zwiener R J, Bowman W P, Winick N J
Department of Pediatrics, University of Texas Southwestern Medical Center, Children's Medical Center, Dallas 75235-9063, USA.
J Clin Oncol. 1997 Apr;15(4):1560-6. doi: 10.1200/JCO.1997.15.4.1560.
The clinical significance of methotrexate (MTX)-induced hepatic toxicity in children with acute lymphoblastic leukemia (ALL) is poorly defined. Therefore, we conducted a study to determine whether intensive MTX therapy could be safely delivered despite isolated serum ALT elevations in children with ALL.
A total of 243 children with B-precursor ALL were treated with extended pulses of oral divided-dose MTX (dMTX). Serum ALT levels were measured approximately every 7 weeks during therapy, as well as after its cessation. By protocol design, treatment was continued without modification in the presence of ALT elevations if there was no other evidence of liver dysfunction.
Of 239 assessable patients, 159 (66.5%) had an ALT level > or = 180 IU/L during therapy and 28 patients (17.6%) had one or more values > or = 720 IU/L. After the completion of therapy, only 17 of 104 assessable patients have had one or more elevated ALT value. Eight of these 17 patients (47%) are hepatitis C virus (HCV)-seropositive. The remaining nine children had subsequent normal or near normal ALT values, and none have clinical evidence of liver disease.
Our data show that MTX can be safely delivered without dose modification in patients with isolated ALT elevations and that continued therapy does not lead to clinically apparent liver disease. ALT elevations are not a reliable predictor of the presence or extent of hepatic injury, and persistently increased ALT values following the completion of ALL therapy are rare in the absence of HCV infection. Continued MTX therapy allows for increased dose-intensity and may improve outcome in children with ALL.
甲氨蝶呤（MTX）诱导的肝毒性在急性淋巴细胞白血病（ALL）患儿中的临床意义尚不明确。因此，我们开展了一项研究，以确定在ALL患儿中，尽管出现孤立性血清谷丙转氨酶（ALT）升高，强化MTX治疗是否仍能安全进行。
共243例B前体ALL患儿接受了口服分剂量MTX（dMTX）的延长脉冲治疗。治疗期间及治疗结束后，大约每7周测量一次血清ALT水平。根据方案设计，如果没有其他肝功能不全的证据，在ALT升高的情况下治疗可继续且无需调整。
在239例可评估患者中，159例（66.5%）在治疗期间ALT水平≥180 IU/L，28例（17.6%）有一个或多个值≥720 IU/L。治疗结束后，104例可评估患者中只有17例有一个或多个ALT值升高。这17例患者中有8例（47%）丙型肝炎病毒（HCV）血清学阳性。其余9名儿童随后ALT值正常或接近正常，且均无肝病的临床证据。
我们的数据表明，对于孤立性ALT升高的患者，MTX可安全给药且无需调整剂量，持续治疗不会导致临床上明显的肝病。ALT升高并非肝损伤存在或程度的可靠预测指标，在无HCV感染的情况下，ALL治疗结束后ALT值持续升高的情况很少见。持续MTX治疗可提高剂量强度，并可能改善ALL患儿的预后。
