Department of Pediatrics and the Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Division of Pediatric Hematology-Oncology, Children's Hospital Los Angeles, Norris Comprehensive Cancer Center and Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Leukemia. 2024 Nov;38(11):2382-2394. doi: 10.1038/s41375-024-02395-4. Epub 2024 Sep 11.
Limited prognostic factors have been associated with overall survival (OS) post-relapse in childhood Acute Lymphoblastic Leukemia (ALL). Patients enrolled on 12 Children's Oncology Group frontline ALL trials (1996-2014) were analyzed to assess for additional prognostic factors associated with OS post-relapse. Among 16,115 patients, 2053 (12.7%) relapsed. Relapse rates were similar for B-ALL (12.5%) and T-ALL (11.2%) while higher for infants (34.2%). Approximately 50% of B-ALL relapses occurred late (≥36 months) and 72.5% involved the marrow. Conversely, 64.8% of T-ALL relapses occurred early (<18 months) and 47.1% involved the central nervous system. The 5-year OS post-relapse for the entire cohort was 48.9 ± 1.2%; B-ALL:52.5 ± 1.3%, T-ALL:35.5 ± 3.3%, and infant ALL:21.5 ± 3.9%. OS varied by early, intermediate and late time-to-relapse; 25.8 ± 2.4%, 49.5 ± 2.2%, and 66.4 ± 1.8% respectively for B-ALL and 29.8 ± 3.9%, 33.3 ± 7.6%, 58 ± 9.8% for T-ALL. Patients with ETV6::RUNX1 or Trisomy 4 + 10 had median time-to-relapse of 43 months and higher OS post-relapse 74.4 ± 3.1% and 70.2 ± 3.6%, respectively. Patients with hypodiploidy, KMT2A-rearrangement, and TCF3::PBX1 had short median time-to-relapse (12.5-18 months) and poor OS post-relapse (14.2 ± 6.1%, 31.9 ± 7.7%, 36.8 ± 6.6%). Site-of-relapse varied by cytogenetic subtype. This large dataset provided the opportunity to identify risk factors for OS post-relapse to inform trial design and highlight populations with dismal outcomes post-relapse.
在儿童急性淋巴细胞白血病（ALL）复发后，只有少数预后因素与总生存期（OS）相关。本研究分析了 1996 年至 2014 年期间，12 项儿童肿瘤协作组（COG）一线 ALL 临床试验中入组的患者，以评估与复发后 OS 相关的其他预后因素。在 16115 例患者中，2053 例（12.7%）复发。B-ALL（12.5%）和 T-ALL（11.2%）的复发率相似，而婴儿的复发率较高（34.2%）。大约 50%B-ALL 复发发生在晚期（≥36 个月），72.5%累及骨髓。相反，64.8%的 T-ALL 复发发生在早期（<18 个月），47.1%累及中枢神经系统。整个队列的复发后 5 年 OS 为 48.9±1.2%；B-ALL：52.5±1.3%，T-ALL：35.5±3.3%，婴儿 ALL：21.5±3.9%。OS 因复发时间的早晚而不同；B-ALL 早期、中期和晚期的 OS 分别为 25.8±2.4%、49.5±2.2%和 66.4±1.8%，T-ALL 分别为 29.8±3.9%、33.3±7.6%和 58±9.8%。ETV6::RUNX1 或三体 4+10 的患者复发中位时间为 43 个月，复发后 OS 分别为 74.4±3.1%和 70.2±3.6%。低倍体、KMT2A 重排和 TCF3::PBX1 的患者复发中位时间较短（12.5-18 个月），复发后 OS 较差（14.2±6.1%、31.9±7.7%、36.8±6.6%）。细胞遗传学亚型不同，复发部位也不同。本大数据集提供了识别复发后 OS 风险因素的机会，以指导临床试验设计，并突出复发后预后不良的人群。
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