美国基因组血统对亚马逊地区急性淋巴细胞白血病患儿严重毒性反应的影响。

Effect of American genomic ancestry on severe toxicities in children with acute lymphoblastic leukemia in the Amazon region.

作者信息

Wanderley Alayde Vieira, de Moraes Francisco Cezar Aquino, da Costa Nunes Giovanna Gilioli, Pereira Esdras Edgar Batista, Leitão Luciana Pereira Colares, de Oliveira Marcelo Braga, Tavares Ágatha Tereza Miranda, da Costa Pantoja Laudreisa, Khayat Bruna Cláudia Meireles, Fernandes Marianne Rodrigues, de Assumpção Paulo Pimentel, Dos Santos Ândrea Kely Ribeiro, Burbano Rommel Mario Rodríguez, Dos Santos Sidney Emanuel Batista, Ribeiro Raul, Khayat André Salim, Dos Santos Ney Pereira Carneiro

机构信息

Otávio Lobo Children's Cancer Hospital-Belém, Belém, PA, 66063-240, Brazil.

Oncology Research Center, Federal University of Pará, University Hospital João de Barros de Barreto. , Rua Dos Mundurucus, no 4487, Belem, PA, 66073-005, Brazil.

出版信息

Discov Oncol. 2024 May 18;15(1):171. doi: 10.1007/s12672-024-01014-z.

DOI:10.1007/s12672-024-01014-z

PMID:38761320

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11102409/

Abstract

BACKGROUND

Acute Lymphoblastic Leukemia (ALL) is a neoplasm of the hematopoietic system characterized by a clonal expansion of abnormal lymphocyte precursor cells. ALL is the most common form of cancer in children, but despite advances in treatment, it can still be fatal. Ethnic differences influence survival rates, and genomic ancestry plays an important role, especially in mixed-race populations such as Latin America. This study aims to analyze the influence of genomic ancestry on toxicity in children with ALL in the Amazon region.

METHODS

The study included 171 patients (protocol number 119,649/2012-Ethics Committee) with ALL treated at a pediatric treatment center in Belém do Pará, in the Brazilian Amazon. The patients were submitted to the BFM protocol of induction therapy for ALL. Toxicity was assessed based on laboratory tests and adverse events, classified according to the CTC-NCI guide. Genomic ancestry was determined using autosomal informative markers.

RESULTS

The majority of children (94.74%) developed some type of toxicity during treatment, 87.04% of which were severe. Infectious toxicity was the most common, present in 84.8% of cases, 77.24% of which were severe. Amerindian ancestry showed an association with the risk of severe general toxicity and severe infectious toxicity, with a contribution of 35.0% demonstrating a significant increase in risk. In addition, post-induction refractoriness and relapse were also associated with an increased risk of death.

CONCLUSION

This study highlights the influence of Amerindian genomic ancestry on response to therapy and toxicity in children with ALL in the Amazon region. Understanding these associations can contribute to personalizing treatment and improving clinical outcomes.

摘要

背景

急性淋巴细胞白血病（ALL）是一种造血系统肿瘤，其特征是异常淋巴细胞前体细胞的克隆性扩增。ALL是儿童中最常见的癌症形式，但尽管治疗取得了进展，它仍然可能致命。种族差异影响生存率，基因组血统起着重要作用，尤其是在拉丁美洲等混血人群中。本研究旨在分析基因组血统对亚马逊地区ALL儿童毒性的影响。

方法

该研究纳入了171例ALL患者（方案编号119,649/2012 - 伦理委员会），这些患者在巴西亚马逊地区帕拉州贝伦的一家儿科治疗中心接受治疗。患者接受了ALL诱导治疗的BFM方案。根据实验室检查和不良事件评估毒性，并根据美国国立癌症研究所（NCI）的常见毒性标准（CTC）进行分类。使用常染色体信息标记确定基因组血统。

结果

大多数儿童（94.74%）在治疗期间出现了某种类型的毒性，其中87.04%为严重毒性。感染性毒性最为常见，84.8%的病例出现，其中77.24%为严重感染性毒性。美洲印第安人血统与严重全身毒性和严重感染性毒性的风险相关，其贡献率为35.0%，表明风险显著增加。此外，诱导后难治性和复发也与死亡风险增加相关。