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

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

Alayde Vieira Wanderley  1 , Francisco Cezar Aquino de Moraes  2 , Giovanna Gilioli da Costa Nunes  3 , Esdras Edgar Batista Pereira  3 , Luciana Pereira Colares Leitão  4 , Marcelo Braga de Oliveira  3 , Ágatha Tereza Miranda Tavares  3 , Laudreisa da Costa Pantoja  3 , Bruna Cláudia Meireles Khayat  3 , Marianne Rodrigues Fernandes  3 , Paulo Pimentel de Assumpção  3 , Ândrea Kely Ribeiro Dos Santos  5 , Rommel Mario Rodríguez Burbano  6 , Sidney Emanuel Batista Dos Santos  5 , Raul Ribeiro  7 , André Salim Khayat  3 , Ney Pereira Carneiro Dos Santos  3
Affiliations

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

Alayde Vieira Wanderley et al. Discov Oncol. .

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.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Genomic ancestry of children with Acute Lymphoid Leukemia, due to the development of severe toxicity. The proximity at each apex of the triangle represents how positively correlated ancestry is with the development of toxicity. EUR European, AFR African, AMR Amerindian
Fig. 2
Fig. 2
Variation in the odds ratios recorded for different distributions of genomic ancestry for severe general toxicity in patients with ALL in the Amazon Region
Fig. 3
Fig. 3
Variation in the odds ratios recorded for different distributions of genomic ancestry for severe infectious toxicity in patients with ALL in the Amazon Region
See this image and copyright information in PMC

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