Determinants of survival after first relapse of acute lymphoblastic leukemia: a Children’s Oncology Group study,Leukemia

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Determinants of survival after first relapse of acute lymphoblastic leukemia: a Children’s Oncology Group study
Leukemia ( IF 12.8 ) Pub Date : 2024-09-11 , DOI: 10.1038/s41375-024-02395-4
Susan R Rheingold ₁ , Deepa Bhojwani ₂ , Lingyun Ji ₃ , Xinxin Xu ₄ , Meenakshi Devidas ₅ , John A Kairalla ₆ , Mary Shago ₇ , Nyla A Heerema ₈ , Andrew J Carroll ₉ , Heather Breidenbach ₁₀ , Michael Borowitz ₁₁ , Brent L Wood ₁₂ , Anne L Angiolillo ₁₃ , Barbara L Asselin ₁₄ , W Paul Bowman ₁₅ , Patrick Brown ₁₆ , ZoAnn E Dreyer ₁₇ , Kimberly P Dunsmore ₁₈ , Joanne M Hilden ₁₉ , Eric Larsen ₂₀ , Kelly Maloney ₁₉ , Yousif Matloub ₂₁ , Leonard A Mattano ₂₂ , Stuart S Winter ₂₃ , Lia Gore ₁₉ , Naomi J Winick ₂₄ , William L Carroll ₂₅ , Stephen P Hunger ₁ , Elizabeth A Raetz ₂₅ , Mignon L Loh ₂₆

Affiliation

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.
Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Children's Oncology Group, Monrovia, CA, USA.
Department of Global Pediatric Medicine, St Jude Children's Research Hospital, Memphis, TN, USA.
Department of Biostatistics, University of Florida, Gainesville, FL, USA.
Department of Laboratory Medicine and Pathobiology, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
Department of Pathology, The Ohio State University, Columbus, OH, USA.
Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA.
The Hospital for Sick Children, Toronto, ON, Canada.
Department of Pathology and Oncology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Department of Pathology and Laboratory Medicine, Childrens Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Servier Pharmaceuticals, Boston, MA, USA.
Department of Pediatrics, Golisano Children's Hospital, Wilmot Cancer Center at University of Rochester Medical Center, Rochester, New York, NY, USA.
Cook Children's Medical Center, Fort Worth, TX, USA.
Bristol Myers Squibb, Princeton, NJ, USA.
Department of Pediatrics, Section of Hematology/Oncology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.
Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, VA, USA.
Department of Pediatrics, University of Colorado School of Medicine and Center for Cancer and Blood Disorders, Children's Hospital Colorado, Aurora, CO, USA.
Department of Pediatrics, Maine Medical Center, Portland, ME, USA.
Department of Pediatrics, Case Western Reserve University, Cleveland, OH, USA.
HARP Pharma Consulting, Mystic, CT, USA.
Cancer and Blood Disorders Program, Children's Minnesota, Minneapolis, MN, USA.
Department of Pediatrics, University of Texas Southwestern Medical Center, Childrens Health, Dallas, TX, USA.
Perlmutter Cancer Center, Department of Pediatrics, NYU Grossman School of Medicine, New York, NY, USA.
Department of Pediatrics, Seattle Children's Hospital, Seattle, WA, USA.

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.

中文翻译：

急性淋巴细胞白血病首次复发后生存的决定因素：儿童肿瘤学组研究

有限的预后因素与儿童急性淋巴细胞白血病（ALL）复发后的总生存期（OS）相关。对 12 项儿童肿瘤组一线 ALL 试验（1996-2014）入组的患者进行了分析，以评估与复发后 OS 相关的其他预后因素。在 16,115 名患者中，2053 名（12.7%）复发。B-ALL （12.5%）和 T-ALL （11.2%）的复发率相似，而婴儿（34.2%）的复发率更高。大约 50% 的 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。整个队列复发后的 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 因早期、中期和晚期复发时间而异;B-ALL 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%、58 ± 9.8%。ETV6：：RUNX1 或三体 4 + 10 患者的中位复发时间为 43 个月，复发后 OS 分别为 74.4 ± 3.1% 和 70.2 ± 3.6%。低二倍体、 KMT2A 重排和 TCF3：:P BX1 患者的中位复发时间较短（12.5-18 个月）和复发后 OS 差（14.2 ± 6.1% 、 31.9 ± 7.7% 、 36.8 ± 6.6%）。复发部位因细胞遗传学亚型而异。这个大型数据集提供了确定复发后 OS 风险因素的机会，以便为试验设计提供信息并突出复发后结果不佳的人群。

更新日期：2024-09-11

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