低风险B细胞急性淋巴细胞白血病中有利的三体异常与治愈预测：儿童肿瘤协作组AALL0331试验结果
Favorable Trisomies and Predict Cure in Low-Risk B-Cell Acute Lymphoblastic Leukemia: Results From Children's Oncology Group Trial AALL0331.
作者信息
Mattano Leonard A, Devidas Meenakshi, Maloney Kelly W, Wang Cindy, Friedmann Alison M, Buckley Patrick, Borowitz Michael J, Carroll Andrew J, Gastier-Foster Julie M, Heerema Nyla A, Kadan-Lottick Nina S, Matloub Yousif H, Marshall David T, Stork Linda C, Loh Mignon L, Raetz Elizabeth A, Wood Brent L, Hunger Stephen P, Carroll William L, Winick Naomi J
机构信息
HARP Pharma Consulting, Mystic, CT.
Department of Global Pediatric Medicine, St Jude Children's Research Hospital, Memphis, TN.
出版信息
J Clin Oncol. 2021 May 10;39(14):1540-1552. doi: 10.1200/JCO.20.02370. Epub 2021 Mar 19.
PURPOSE
Children's Oncology Group (COG) AALL0331 tested whether pegaspargase intensification on a low-intensity chemotherapy backbone would improve the continuous complete remission (CCR) rate in a low-risk subset of children with standard-risk B-acute lymphoblastic leukemia (ALL).
METHODS
AALL0331 enrolled 5,377 patients with National Cancer Institute standard-risk B-ALL (age 1-9 years, WBC < 50,000/μL) between 2005 and 2010. Following a common three-drug induction, a cohort of 1,857 eligible patients participated in the low-risk ALL random assignment. Low-risk criteria included no extramedullary disease, < 5% marrow blasts by day 15, end-induction marrow minimal residual disease < 0.1%, and favorable cytogenetics ( fusion or simultaneous trisomies of chromosomes 4, 10, and 17). Random assignment was to standard COG low-intensity therapy (including two pegaspargase doses, one each during induction and delayed intensification) with or without four additional pegaspargase doses at 3-week intervals during consolidation and interim maintenance. The study was powered to detect a 4% improvement in 6-year CCR rate from 92% to 96%.
RESULTS
The 6-year CCR and overall survival (OS) rates for the entire low-risk cohort were 94.7% ± 0.6% and 98.7% ± 0.3%, respectively. The CCR rates were similar between arms (intensified pegaspargase 95.3% ± 0.8% standard 94.0% ± 0.8%; = .13) with no difference in OS (98.1% ± 0.5% 99.2% ± 0.3%; = .99). Compared to a subset of standard-risk study patients given identical therapy who had the same early response characteristics but did not have favorable or unfavorable cytogenetics, outcomes were significantly superior for low-risk patients (CCR hazard ratio 1.95; = .0004; OS hazard ratio 5.42; < .0001).
CONCLUSION
Standard COG therapy without intensified pegaspargase, which can easily be given as an outpatient with limited toxicity, cures nearly all children with B-ALL identified as low-risk by clinical, early response, and favorable cytogenetic criteria.
目的
儿童肿瘤协作组（COG）的AALL0331试验旨在探究在低强度化疗基础上加用聚乙二醇天冬酰胺酶强化治疗，是否能提高标准风险B系急性淋巴细胞白血病（ALL）低风险亚组患儿的持续完全缓解（CCR）率。
方法
AALL0331在2005年至2010年间纳入了5377例符合美国国立癌症研究所标准风险B-ALL的患者（年龄1 - 9岁，白细胞计数<50,000/μL）。在进行常见的三药诱导治疗后，1857例符合条件的患者参与了低风险ALL随机分组。低风险标准包括无髓外疾病、第15天骨髓原始细胞<5%、诱导结束时骨髓微小残留病<0.1%以及良好的细胞遗传学特征（t(12;21)融合或同时存在4号、10号和17号染色体三体）。随机分组为接受标准的COG低强度治疗（包括两剂聚乙二醇天冬酰胺酶，诱导期和延迟强化期各一剂），巩固期和中期维持期间隔3周再额外给予四剂聚乙二醇天冬酰胺酶或不给予。该研究旨在检测6年CCR率从92%提高到96%的4%改善情况。
结果
整个低风险队列的6年CCR率和总生存率（OS）分别为94.7%±0.6%和98.7%±0.3%。两组的CCR率相似（强化聚乙二醇天冬酰胺酶组为95.3%±0.8%，标准组为94.0%±0.8%；P = 0.13），OS无差异（98.1%±0.5%对99.2%±0.3%；P = 0.99）。与一组接受相同治疗、具有相同早期反应特征但无良好或不良细胞遗传学特征的标准风险研究患者相比，低风险患者的预后显著更好（CCR风险比1.95；P = 0.0004；OS风险比5.42；P < 0.0001）。
结论
标准的COG治疗方案（不强化聚乙二醇天冬酰胺酶），毒性有限且可轻松门诊给药，能治愈几乎所有经临床、早期反应和良好细胞遗传学标准确定为低风险的B-ALL患儿。
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