Brugières Laurence, Le Deley Marie-Cécile, Rosolen Angelo, Williams Denise, Horibe Keizo, Wrobel Grazyna, Mann Georg, Zsiros Jozsef, Uyttebroeck Anne, Marky Ildiko, Lamant Laurence, Reiter Alfred
Department of Pediatric Oncology and Biostatistics and Epidemiology Unit, Institut Gustave-Roussy, 39, rue Camille Desmoulins, 94805 Villejuif Cedex, France.
J Clin Oncol. 2009 Feb 20;27(6):897-903. doi: 10.1200/JCO.2008.18.1487. Epub 2009 Jan 12.
To compare the efficacy and safety of two methotrexate doses and administration schedules in children with anaplastic large-cell lymphoma (ALCL).
This randomized trial for children with ALCL was based on the Non-Hodgkin's Lymphoma-Berlin-Frankfurt-Muenster 90 (NHL-BFM90) study protocol and compared six courses of methotrexate 1 g/m2 over 24 hours and an intrathecal injection (IT) followed by folinic acid rescue at 42 hours (MTX1 arm) with six courses of methotrexate 3 g/m2 over 3 hours followed by folinic acid rescue at 24 hours without IT (MTX3 arm). This trial involved most European pediatric/lymphoma study groups and a Japanese group.
Overall, 352 patients (96% ALK positive) were recruited between 1999 and 2005; 175 were randomly assigned to the MTX1 arm, and 177 were assigned to the MTX3 arm. Ninety-two percent of patients received protocol treatment. Median follow-up time is 3.7 years. Event-free survival (EFS) curves were superimposed with 2-year EFS rates (73.6% and 74.5% in the MTX1 and MTX3 arms, respectively; hazard ratio = 0.98; 91.76% CI, 0.69 to 1.38). Two-year overall survival rates were 90.1% and 94.9% in MTX1 and MTX3, respectively. Only two CNS relapses occurred (both in the MTX1 arm). Toxicity was assessed after 2,050 courses and included grade 4 hematologic toxicity after 79% and 64% of MTX1 and MTX3 courses, respectively (P < .0001); infection after 50% and 32% of courses, respectively (P < .0001); and grade 3 to 4 stomatitis after 21% and 6% of courses, respectively (P < .0001).
The results of the NHL-BFM90 study were reproduced in this large international trial. The methotrexate schedule of the NHL-BFM90 protocol including IT therapy can be safely replaced by a less toxic schedule of methotrexate 3 g/m2 in a 3-hour infusion without IT therapy.
比较两种甲氨蝶呤剂量及给药方案治疗间变性大细胞淋巴瘤（ALCL）患儿的疗效和安全性。
这项针对ALCL患儿的随机试验基于非霍奇金淋巴瘤-柏林-法兰克福-明斯特90（NHL-BFM90）研究方案，比较了甲氨蝶呤1 g/m²在24小时内静脉滴注并鞘内注射（IT），随后在42小时给予亚叶酸解救（MTX1组）与甲氨蝶呤3 g/m²在3小时内静脉滴注，随后在24小时给予亚叶酸解救且不进行IT治疗（MTX3组）这两种方案，共六个疗程。该试验涉及大多数欧洲儿科/淋巴瘤研究组以及一个日本研究组。
总体而言，1999年至2005年间招募了352例患者（96%为ALK阳性）；175例被随机分配至MTX1组，177例被分配至MTX3组。92%的患者接受了方案治疗。中位随访时间为3.7年。无事件生存（EFS）曲线相互重叠，MTX1组和MTX3组的2年EFS率分别为73.6%和74.5%；风险比 = 0.98；91.76%可信区间为0.69至1.38。MTX1组和MTX3组的2年总生存率分别为90.1%和94.9%。仅发生了2例中枢神经系统复发（均在MTX1组）。在2050个疗程后评估毒性，MTX1组和MTX3组分别有79%和64%的疗程出现4级血液学毒性（P < 0.0001）；分别有50%和32%的疗程出现感染（P < 0.0001）；分别有21%和6%的疗程出现3至4级口腔炎（P < 0.0001）。
在这项大型国际试验中重现了NHL-BFM90研究的结果。NHL-BFM90方案中包括IT治疗的甲氨蝶呤给药方案可被毒性较低的甲氨蝶呤3 g/m²在3小时内静脉滴注且不进行IT治疗的方案安全替代。
