Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932
Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932
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DOI：
10.1200/jco.20.00494
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发表时间：
2021-05-01
影响因子：
45.3
通讯作者：
Hunger, Stephen P.
中科院分区：
文献类型：
--
作者：
Angiolillo, Anne L.;Schore, Reuven J.;Hunger, Stephen P.
目的：AALL 0932评估了两种随机维持干预措施，以优化新诊断的NCI标准风险（SR）B-急性淋巴细胞白血病（B-ALL）儿童的无病生存期（DFS），同时减轻治疗负担。2，364名平均风险（AR）患者被随机分配（2 x 2析因设计）在长春新碱/地塞米松脉冲维持治疗开始时，每4结果：入选的所有合格和可评估的SR B-ALL患者（n = 9，226）的5年无事件生存率和总生存率（OS）（95%CI）分别为92.0%（91.1%和92.8%）和96.8%（96.2%和97.3%）。随机分配的AR患者从维持治疗开始的5年DFS和OS分别为94.6%（93.3%和95.9%）和98.5%（97.7%和99.2%）。随机分配接受VCR/DEX治疗的患者的5年DFS和OS 4（n = 1，186）对比VCR/DEX 12（n = 1，178）分别为94.1%（92.2%和96.0%）和98.3%（97.2%和99.4%）vs 95.1%（93.3%和96.9%）和98.6%（97.7%和99.6%）（P = 0.86和0.69）。随机分配接受MTX 20与MTX 40的AR患者的5年DFS和OS为95.1%（93.3%和96.8%）和98.8%（97.9%和99.7%）v 94.2%（92.2%和96.1%）和98.1%（97.0%和99.2%）（P = 0.92和0.89）。接受VCR/DEX 12治疗的0 NCI-SR AR B-ALL患者尽管接受了三分之一的长春新碱，但结局出色。地塞米松脉冲先前用作儿童肿瘤组（COG）试验的标准治疗。与20 mg/m2/周相比，MTX的起始剂量40 mg/m2/周并没有改善结局。降低长春新碱/地塞米松脉冲频率已纳入一线COG B-ALL试验，以减轻患者及其家属的治疗负担。
Purpose:AALL0932 evaluated two randomized maintenance interventions to optimize disease-free survival (DFS) while reducing the burden of therapy in children with newly diagnosed NCI standard-risk (SR) B-acute lymphoblastic leukemia (B-ALL).Methods:AALL0932 enrolled 9,229 patients with B-ALL; 2,364 average-risk (AR) patients were randomly assigned (2 x 2 factorial design) at the start of maintenance therapy to vincristine/dexamethasone pulses every 4 (VCR/DEX4) or every 12 (VCR/DEX12) weeks, and a starting dose of weekly oral methotrexate of 20 mg/m(2) (MTX20) or 40 mg/m(2) (MTX40).Results:Five-year event-free survival and overall survival (OS) from enrollment (with 95% CIs), for all eligible and evaluable SR B-ALL patients (n = 9,226), were 92.0% (91.1% and 92.8%) and 96.8% (96.2% and 97.3%), respectively. The 5-year DFS and OS from the start of maintenance for randomly assigned AR patients were 94.6% (93.3% and 95.9%) and 98.5% (97.7% and 99.2%), respectively. The 5-year DFS and OS for patients randomly assigned to receive VCR/DEX4 (n = 1,186) versus VCR/DEX12 (n = 1,178) were 94.1% (92.2% and 96.0%) and 98.3% (97.2% and 99.4%) v 95.1% (93.3% and 96.9%) and 98.6% (97.7% and 99.6%), respectively (P = .86 and .69). The 5-year DFS and OS for AR patients randomly assigned to receive MTX20 versus MTX40 were 95.1% (93.3% and 96.8%) and 98.8% (97.9% and 99.7%) v 94.2% (92.2% and 96.1%) and 98.1% (97.0% and 99.2%), respectively (P = .92 and .89).Conclusions:The 0NCI-SR AR B-ALL who received VCR/DEX12 had outstanding outcomes despite receiving one third of the vincristine/dexamethasone pulses previously used as standard of care on Children's Oncology Group (COG) trials. The higher starting dose of MTX of 40 mg/m(2)/week did not improve outcomes when compared with 20 mg/m(2)/week. The decreased frequency of vincristine/dexamethasone pulses has been incorporated into frontline COG B-ALL trials to decrease the burden of therapy for patients and their families.