The impact of the methotrexate administration schedule and dose in the treatment of children and adolescents with B-cell neoplasms: a report of the BFM Group Study NHL-BFM95
The impact of the methotrexate administration schedule and dose in the treatment of children and adolescents with B-cell neoplasms: a report of the BFM Group Study NHL-BFM95
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DOI：
10.1182/blood-2004-03-0973
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发表时间：
2005-02-01
期刊：
影响因子：
20.3
通讯作者：
Reiter, A
中科院分区：
文献类型：
--
作者：
Woessmann, W;Seidemann, K;Reiter, A
在非霍奇金淋巴瘤-柏林-法兰克福-明斯特95（NHL-BFM 95）研究中，我们通过随机化测试了B细胞肿瘤患者静脉输注甲氨蝶呤4小时（MTX-4 h）是否不劣于但毒性低于24小时静脉输注（MTX-24 h）。其次，我们根据研究NHL-BFM 90的历史对照研究，研究了中度肿瘤患者的MTX是否可以从5 g/m2降至1 g/m2。R1组（切除组）、R2组（LDH < 500 U/L）、R3组（LDH > 500 ~< 1000 U/L）和R4组（LDH > 1000 U/L和/或中枢神经系统疾病）分别接受2个5 d疗程的治疗。在填充+ R2和R3 + R4中，课程含有MTX 1 g/m（2）和5 g/m（2）。在505例患者中（1996年4月至2001年3月），364例随机接受MTX-4 h或MTX-24 h。无失败生存期MTX-4 h组与MTX-24 h组的pFFS（1年）分别为95% +/- 5%（n 20）与100%（n = 19），R2为94% +/- 2%（n = 88）与96% +/- 2%（n = 95），R3 +/- R4中为77% +/- 5%（n 62）与93% +/- 3%（n = 69）（符合方案分析）。在所有风险组中，MTX-4 h组III/IV级粘膜炎的发生率显著降低。对于R2中的患者，NHL-BFM 95（MTX 1 g/m2）和NHL-BFM 90（MTX 5 g/m2）中的无事件生存率（pEFS）分别为95% ± 2%（n = 222）和97% ± 1%（n = 154）。总之，MTX-4 h的毒性低于MTX-24 h。对于局限期B细胞非霍奇金淋巴瘤（B-NHL），MTX-4 h不劣于MTX-24 h，但对于晚期疾病，MTX-4 h不劣于MTX-24 h。对于局限性疾病，MTX 1 g/m2不劣于5 g/m2。(C)2005年美国血液学会。
In the Non-Hodgkin Lymphoma-Berlin-Frankfurt-Munster 95 (NHL-BFM95) study, we tested by randomization whether for patients with B-cell neoplasms methotrexate as intravenous infusion over 4 hours (MTX-4h) is not inferior to, but less toxic than, a 24-hour intravenous infusion (MTX-24h). Second, we investigated against the historical control of study NHL-BFM90, whether for patients with moderate tumor mass MTX can be reduced from 5 g/m(2) to 1 g/m(2). Patients received 2 5-day therapy courses in risk group R1 (resected), 4 in R2 (lactate dehydrogenase [LDH] < 500 U/L), 5 in R3 (LDH > 500 to < 1000 U/L) and 6 in R4 (LDH > 1000 U/L and/or central nervous system [CNS] disease). Courses contained MTX 1 g/m(2) in Fill + R2 and 5 g/m(2) in R3 + R4. Of 505 patients (April 1996 to March 2001), 364 were randomized to receive MTX-4h or MTX-24h. Failure-free survival (pFFS, 1 year) for arm MTX-4h versus MTX-24h, respectively, was 95% +/- 5% (n 20) versus 100% (n = 19) in R1, 94% +/- 2% (n = 88) versus 96% +/- 2% (n = 95) in R2, and 77% +/- 5% (n 62) versus 93% +/- 3% (n = 69) in R3 +/- R4 (per-protocol analysis). Incidence of mucositis grade III/IV was significantly lower with MTX-4h in all risk groups. For patients in R2, event-free survival (pEFS) was 95% +/- 2% (n = 222) in NHL-BFM95 (MTX 1 g/m(2)) and 97% +/- 1% (n = 154) in NHL-BFM90 (MTX 5 g/m(2)). In conclusion, MTX-4h was less toxic than MTX-24h. MTX-4h was noninferior to MTX-24h for limited stage B-cell non-Hodgkin lymphoma (B-NHL) but not for advanced disease. For limited disease, MTX 1 g/m(2) is noninferior to 5 g/m(2). (C) 2005 by The American Society of Hematology.