Treatment-related adverse events associated with a modified UK ALLR3 induction chemotherapy backbone for childhood relapsed/refractory acute lymphoblastic leukemia.
Treatment-related adverse events associated with a modified UK ALLR3 induction chemotherapy backbone for childhood relapsed/refractory acute lymphoblastic leukemia.
复制标题
DOI：
10.1002/pbc.26129
复制
发表时间：
2016-11
影响因子：
3.2
通讯作者：
Wayne AS
中科院分区：
文献类型：
--
作者：
Sun W;Orgel E;Malvar J;Sposto R;Wilkes JJ;Gardner R;Tolbert VP;Smith A;Hur M;Hoffman J;Rheingold SR;Burke MJ;Wayne AS
英国ALLR3 （R3）方案已被美国许多中心用于治疗儿童复发性急性淋巴细胞白血病（ALL），并已成为在临床试验中测试新药的首选治疗骨干。该平台的详细毒性资料此前未见报道。首次复发后的毒性和反应率尚不清楚。我们进行了一项多机构、回顾性研究，包括在五个儿科中心接受R3再诱导化疗主干阻断1治疗的复发性ALL儿童。从病历中提取数据并进行分析。59例患者纳入研究，其中16例复发≥2次。97%的患者经历了至少一次≥3级非血液学不良事件（AE）。90%的患者报告了3级或更高的感染。其他非血液学≥3级ae包括电解质异常、肝酶升高和疼痛。85%的患者达到了完全缓解（CR）。第1次或≥2次复发患者的ae发生率、CR率和最小残留病阴性率无显著差异。我们的研究证实R3 block 1是儿童复发ALL的一种高度活跃的再诱导方案。然而，它与严重毒性，特别是感染的高发率有关。我们报告中描述的毒性应用于R3骨干的最佳支持治疗和未来临床试验设计，特别是当新药物与该方案联合使用时。
The UK ALLR3 (R3) regimen has been adopted to treat pediatric relapsed acute lymphoblastic leukemia (ALL) by many centers in the United States and has become a preferred therapeutic backbone for testing novel agents in clinical trials. A detailed toxicity profile of this platform has not previously been reported. The toxicity and response rates for its use beyond first relapse are unknown. We performed a multi-institutional, retrospective study including children with relapsed ALL treated with the R3 reinduction chemotherapy backbone block 1 across five pediatric centers. Data were extracted from medical records and analyzed. Fifty-nine patients were included in the study, including 16 patients with ≥2nd relapse. Ninety-seven percent of patients experienced at least one Grade ≥3 nonhematologic adverse event (AE). Grade 3 or higher infection was reported in 90% of patients. Other nonhematologic Grade ≥3 AEs included electrolyte abnormalities, elevation in hepatic enzymes, and pain. Eighty-five percent of patients achieved a complete remission (CR). There were no significant differences in the incidence of AEs, CR rate, and rate of minimal residual disease negativity between patients with 1st or ≥2nd relapse. Our study confirmed that R3 block 1 is a highly active reinduction regimen in childhood relapsed ALL. However, it was associated with a high incidence of severe toxicities, particularly infection. The toxicity profiled in our report should be used to inform optimal supportive care and future clinical trial design with the R3 backbone, particularly when new agents are combined with this regimen.
登录
查看更多内容
影响因子：
45.3
作者：
Tallen, Gesche;Ratei, Richard;von Stackelberg, Arend
通讯作者：
von Stackelberg, Arend
影响因子：
1.8
作者：
Biswal S;Godnaik C
通讯作者：
Godnaik C
影响因子：
20.3
作者：
Messinger, Yoav H.;Gaynon, Paul S.;Bostrom, Bruce C.
通讯作者：
Bostrom, Bruce C.
影响因子：
20.3
作者：
Sung, Lillian;Aplenc, Richard;Gamis, Alan S.
通讯作者：
Gamis, Alan S.
影响因子：
6.2
作者：
Lim, Joshua Yew-Suang;Bhatia, Smita;Robison, Leslie L.;Yang, Jun J.
通讯作者：
Yang, Jun J.