21 号染色体的染色体内扩增与当代标准风险儿童肿瘤组研究中治疗的儿童急性淋巴细胞白血病患者的不良结局相关：来自儿童肿瘤组的报告。
Intrachromosomal amplification of chromosome 21 is associated with inferior outcomes in children with acute lymphoblastic leukemia treated in contemporary standard-risk children's oncology group studies: a report from the children's oncology group.
机构信息
Nyla A. Heerema and Julie M. Gastier-Foster, The Ohio State University Wexner Medical Center; Julie M. Gastier-Foster, The Ohio State University College of Medicine and Nationwide Children's Hospital, Columbus, OH; Andrew J. Carroll, University of Alabama at Birmingham, Birmingham, AL; Meenakshi Devidas, University of Florida, Gainesville, FL; Mignon L. Loh, University of California at San Francisco, San Francisco, CA; Michael J. Borowitz, Johns Hopkins Medical Institutions, Baltimore, MD; Eric C. Larsen, Maine Children's Cancer Program, Scarborough, ME; Leonard A. Mattano Jr, Michigan State University College of Human Medicine, Kalamazoo, MI; Kelly W. Maloney and Stephen P. Hunger, Children's Hospital Colorado and University of Colorado School of Medicine, Aurora, CO; Cheryl L. Willman, University of New Mexico, Albuquerque, NM; Brent L. Wood, University of Washington, Seattle, WA; Naomi J. Winick, University of Texas Southwestern Medical Center, Dallas, TX; and William L. Carroll and Elizabeth A. Raetz, The New York University Cancer Institute, New York University Langone Medical Center, New York, NY.
出版信息
J Clin Oncol. 2013 Sep 20;31(27):3397-402. doi: 10.1200/JCO.2013.49.1308. Epub 2013 Aug 12.
PURPOSE
Five-year overall survival (OS) for children with B-cell precursor acute lymphoblastic leukemia (B-ALL) exceeds 90% with risk-adapted therapy. Age, initial WBC count, genetic aberrations, and minimal residual disease (MRD) are used for risk stratification. Intrachromosomal amplification of a region of chromosome 21 (iAMP21; three or more extra copies of RUNX1 on an abnormal chromosome 21) is a recently identified recurrent genomic lesion associated with inferior outcome in some studies. We investigated the impact of iAMP21 in a large cohort treated in contemporary Children's Oncology Group (COG) ALL trials.
PATIENTS AND METHODS
Fluorescent in situ hybridization for specific genetic aberrations was required at diagnosis. MRD was measured by flow cytometry at end induction. Outcome was measured as event-free survival (EFS) and OS.
RESULTS
iAMP21 was found in 158 (2%) of 7,793 patients with B-ALL age ≥ 1 year; 74 (1.5%) of 5,057 standard-risk (SR) patients, and 84 (3.1%) of 2,736 high-risk (HR) patients. iAMP21 was associated with age ≥ 10 years, WBC less than 50,000/μL, female sex, and detectable MRD at day 29. Four-year EFS and OS were significantly worse for patients with iAMP21 and SR B-ALL, but iAMP21 was not a statistically significant prognostic factor in HR patients. There was no interaction between MRD and iAMP21. Among SR patients, day 29 MRD ≥ 0.01% and iAMP21 were associated with the poorest EFS and OS; absence of both was associated with the best outcome.
CONCLUSION
iAMP21 is associated with inferior outcome in pediatric B-ALL, particularly SR patients who require more intensive therapy and are now treated on HR COG ALL protocols.
目的
采用风险适应疗法，儿童 B 细胞前体急性淋巴细胞白血病（B-ALL）的 5 年总生存率（OS）超过 90%。年龄、初始白细胞计数、遗传异常和微小残留病（MRD）用于风险分层。染色体 21 区域的内染色体扩增（iAMP21；异常染色体 21 上有三个或更多额外的 RUNX1 拷贝）是最近发现的一种与某些研究中不良预后相关的复发性基因组病变。我们在当代儿童肿瘤学组（COG）ALL 试验中对大量接受治疗的患者进行了 iAMP21 的影响研究。
患者和方法
诊断时需要进行特定遗传异常的荧光原位杂交。诱导结束时通过流式细胞术测量 MRD。通过无事件生存（EFS）和 OS 来衡量结果。
结果
在年龄≥ 1 岁的 7793 例 B-ALL 患者中发现了 158 例（2%）iAMP21；在 5057 例标准风险（SR）患者中发现了 74 例（1.5%），在 2736 例高风险（HR）患者中发现了 84 例（3.1%）。iAMP21 与年龄≥ 10 岁、白细胞计数<50,000/μL、女性和第 29 天可检测到的 MRD 有关。携带 iAMP21 的 SR 患者的 4 年 EFS 和 OS 显著较差，但在 HR 患者中，iAMP21 不是统计学上显著的预后因素。MRD 与 iAMP21 之间没有相互作用。在 SR 患者中，第 29 天 MRD≥0.01%和 iAMP21 与最差的 EFS 和 OS 相关；两者均不存在与最佳结果相关。
结论
iAMP21 与儿科 B-ALL 的不良预后相关，尤其是 SR 患者，他们需要更强化的治疗，现在按照 HR COG ALL 方案进行治疗。
Zotero 插件