Bisogno G, de Kraker J, Weirich A, Masiero L, Ludwig R, Tournade M F, Carli M
Department of Pediatrics, University of Padova, Italy.
Med Pediatr Oncol. 1997 Oct;29(4):245-51. doi: 10.1002/(sici)1096-911x(199710)29:4<245::aid-mpo2>3.0.co;2-m.
Hepatotoxicity consistent with the clinical diagnosis of veno-occlusive disease (VOD) of the liver has been suspected after conventional anti-cancer chemotherapy in children.
To establish the incidence of hepatotoxicity and its relationship with VOD, we analyzed toxicity data obtained on 511 children affected by Wilms tumor and treated according to the SIOP-9 protocol. They all received pre- and postnephrectomy chemotherapy using dactinomycin (AD) and vincristine (VCR) +/- other drugs +/- radiotherapy according to surgical stage and histology.
Sixty-four patients suffered at least one episode of hepatotoxicity and 41 satisfied the criteria for a clinical diagnosis of VOD. In this latter group, toxicity occurred during preoperative treatment in 15 patients and was confirmed histopathologically in 9 of the 16 liver biopsies obtained. There was a higher percentage of children aged less than 1 year at diagnosis in the VOD group than in the other patients (24% vs. 11.4%). The degree of liver damage in the younger patients seems important, as suggested by a higher increase in transaminases. VOD developed in 12% of the 68 irradiated children vs. 7% in the non-irradiated group. Statistical analysis showed an increased risk of VOD in younger patients (p < 0.001) and in those receiving radiotherapy (p < 0.001). All patients recovered after 6-180 days using supportive therapy only.
(1) 8% of children treated according to the SIOP-9 protocol, developed hepatotoxicity consistent with VOD. Excluding patients who received radiotherapy, the incidence was 6%. These figures are much higher than in earlier reports, though different diagnostic criteria were used. (2) Chemotherapy with AD and VCR seems to be a major cause of VOD. (3) Risk factors are young age and concomitant radiotherapy. (4) VOD does not prejudice positive outcome for these patients.
儿童接受传统抗癌化疗后，曾怀疑出现与肝静脉闭塞病（VOD）临床诊断相符的肝毒性。
为确定肝毒性的发生率及其与VOD的关系，我们分析了511例患肾母细胞瘤并按照SIOP - 9方案治疗的儿童的毒性数据。他们均根据手术分期和组织学情况，在肾切除术前和术后接受了放线菌素D（AD）和长春新碱（VCR）+/-其他药物+/-放疗。
64例患者至少发生过一次肝毒性发作，41例符合VOD临床诊断标准。在后一组中，15例患者在术前治疗期间出现毒性反应，在获取的16份肝活检标本中有9份经组织病理学证实。VOD组中诊断时年龄小于1岁的儿童比例高于其他患者（24%对11.4%）。正如转氨酶升高幅度较大所表明的，年轻患者的肝损伤程度似乎更为严重。68例接受放疗的儿童中有12%发生VOD，未接受放疗组为7%。统计分析显示，年轻患者（p < 0.001）和接受放疗的患者（p < 0.001）发生VOD的风险增加。所有患者仅采用支持性治疗，6 - 180天后均康复。
（1）按照SIOP - 9方案治疗的儿童中有8%出现了与VOD相符的肝毒性。排除接受放疗的患者，发生率为6%。尽管使用了不同的诊断标准，但这些数字远高于早期报告。（2）AD和VCR化疗似乎是VOD的主要原因。（3）危险因素是年龄小和同时进行放疗。（4）VOD并不影响这些患者的良好预后。
