Weber B L, Tanyer G, Poplack D G, Reaman G H, Feusner J H, Miser J S, Bleyer W A
University of Washington School of Medicine, Seattle.
NCI Monogr. 1987(5):207-12.
Serial liver-enzyme determinations were performed on 36 children with acute lymphoblastic leukemia who were randomized to receive either conventional intrathecal methotrexate (MTX) therapy with cranial irradiation, or an investigational high-dose MTX regimen consisting of 10 courses of 33,600 mg/m2 over 24 hours, with high-dose leucovorin rescue. Both groups of patients received intermittent low-dose oral MTX during maintenance therapy. Serum transaminase elevations in the group of conventionally treated patients were infrequent and moderate in severity (less than 300 IU/liter). In the investigational group, however, the majority of patients had severe, acute increases in SGPT (greater than 300 IU/liter), with peaks up to 1000 to 2000 IU/liter. The incidence and severity of acute transaminasemia were directly proportional to the number of high-dose MTX courses received: courses 1, 2, 3, 4, 5, and 6 caused transaminase elevations in 31%, 50%, 50%, 73%, 100%, and 100% of courses, respectively, and 0%, 14%, 20%, 44%, 55%, and 92%, respectively, were over 300 IU/liter. Patients in both treatment groups developed a pattern of increasing serum alkaline phosphatase concentrations after initiation of low-dose oral MTX therapy; isoenzyme analysis indicated that this effect was osseous rather than hepatic. Serum bilirubin was rarely elevated. Transaminases returned to normal within 1 to 2 weeks after each high-dose MTX treatment, and with follow-up for as long as 7 years, no patient has developed clinical evidence of residual liver disease, after 3 years of high-dose MTX therapy and multiple other antileukemia drugs. The acute hypertransaminasemia frequently observed after high-dose MTX therapy is transient and reversible, and, in children, does not appear to result in chronic liver disease.
对36例急性淋巴细胞白血病患儿进行了系列肝酶测定，这些患儿被随机分为两组，一组接受传统鞘内注射甲氨蝶呤（MTX）联合头颅照射治疗，另一组接受研究性高剂量MTX方案治疗，该方案为在24小时内分10个疗程给予33600mg/m²，并给予高剂量亚叶酸钙解救。两组患者在维持治疗期间均接受间歇性低剂量口服MTX。接受传统治疗的患者组血清转氨酶升高不常见，且严重程度中等（低于300IU/升）。然而，在研究组中，大多数患者的谷丙转氨酶（SGPT）出现严重急性升高（高于300IU/升），峰值高达1000至2000IU/升。急性转氨酶血症的发生率和严重程度与接受高剂量MTX疗程的数量直接相关：第1、2、3、4、5和6个疗程分别导致31%、50%、50%、73%、100%和100%的疗程出现转氨酶升高，分别有0%、14%、20%、44%、55%和92%高于300IU/升。两个治疗组的患者在开始低剂量口服MTX治疗后血清碱性磷酸酶浓度均呈上升趋势；同工酶分析表明这种影响是骨源性而非肝源性的。血清胆红素很少升高。每次高剂量MTX治疗后1至2周内转氨酶恢复正常，在接受高剂量MTX治疗3年及多种其他抗白血病药物治疗后，随访长达7年，没有患者出现残留肝病的临床证据。高剂量MTX治疗后经常观察到的急性高转氨酶血症是短暂且可逆的，在儿童中似乎不会导致慢性肝病。
