Pediatric Hematology/Oncology, Washington School of Medicine, St Louis Children's Hospital, St Louis, MO.
Children's Minnesota Cancer and Blood Disorders Program, Minneapolis, MN.
J Clin Oncol. 2020 Sep 10;38(26):3062-3070. doi: 10.1200/JCO.20.00531. Epub 2020 Jun 17.
The Children's Oncology Group (COG) protocol AALL0434 evaluated the safety and efficacy of multi-agent chemotherapy with Capizzi-based methotrexate/pegaspargase (C-MTX) in patients with newly diagnosed pediatric T-cell lymphoblastic lymphoma (T-LL) and gained preliminary data using nelarabine in high-risk patients.
The trial enrolled 299 patients, age 1-31 years. High-risk (HR) patients had ≥ 1% minimal detectable disease (MDD) in the bone marrow at diagnosis or received prior steroid treatment. Induction failure was defined as failure to achieve a partial response (PR) by the end of the 4-week induction. All patients received the augmented Berlin-Frankfurt-Muenster (ABFM) C-MTX regimen. HR patients were randomly assigned to receive or not receive 6 5-day courses of nelarabine incorporated into ABFM. Patients with induction failure were nonrandomly assigned to ABFM C-MTX plus nelarabine. No patients received prophylactic cranial radiation; however, patients with CNS3 disease (CSF WBC ≥ 5/μL with blasts or cranial nerve palsies, brain/eye involvement, or hypothalamic syndrome) were ineligible.
At end-induction, 98.8% of evaluable participants had at least a PR. The 4-year event-free survival (EFS) and overall survival (OS) were 84.7% ± 2.3% and 89.0% ± 2.0%. The 4-year disease-free survival (DFS) from end-induction was 85.9% ± 2.6%. There was no difference in DFS observed between the HR and standard-risk groups ( = .29) or by treatment regimen ( = .55). Disease stage, tumor response, and MDD at diagnosis did not demonstrate thresholds that resulted in differences in EFS. Nelarabine did not show an advantage for HR patients. CNS relapse occurred in only 4 patients.
COG AALL0434 produced excellent outcomes in one of the largest trials ever conducted for patients with newly diagnosed T-LL. The COG ABFM regimen with C-MTX provided excellent EFS and OS without cranial radiation.
儿童肿瘤学组（COG）方案 AALL0434 评估了基于 Capizzi 的甲氨蝶呤/培门冬酶（C-MTX）联合多药化疗在新诊断的儿科 T 细胞淋巴母细胞淋巴瘤（T-LL）患者中的安全性和疗效，并在高危患者中使用奈拉滨获得了初步数据。
该试验共纳入 299 例年龄 1-31 岁的患者。高危（HR）患者在诊断时骨髓中最小残留疾病（MDD）≥1%或接受过皮质类固醇治疗。诱导失败定义为在 4 周诱导结束时未达到部分缓解（PR）。所有患者均接受增强型柏林-法兰克福-明斯特（ABFM）C-MTX 方案治疗。HR 患者随机分为接受或不接受奈拉滨 6 个 5 天疗程的治疗。诱导失败的患者非随机接受 ABFM C-MTX 联合奈拉滨治疗。没有患者接受预防性颅脑照射；然而，患有中枢神经系统 3 期疾病（CSF WBC≥5/μL，伴有原始细胞或颅神经麻痹、脑/眼受累或下丘脑综合征）的患者不符合入组条件。
在诱导结束时，98.8%的可评估参与者至少有 PR。4 年无事件生存率（EFS）和总生存率（OS）分别为 84.7%±2.3%和 89.0%±2.0%。从诱导结束到无病生存（DFS）的 4 年时间为 85.9%±2.6%。高危组和标准风险组之间（=0.29）或治疗方案之间（=0.55）DFS 无差异。疾病分期、肿瘤反应和诊断时的 MDD 均未显示导致 EFS 差异的阈值。奈拉滨对 HR 患者没有优势。仅有 4 例患者发生中枢神经系统复发。
COG AALL0434 在新诊断的 T-LL 患者中开展的最大规模试验之一中取得了优异的结果。COG ABFM 方案联合 C-MTX 治疗在不进行颅脑照射的情况下提供了优异的 EFS 和 OS。
