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Helpful Criteria When Implementing NGS Panels in Childhood Lymphoblastic Leukemia.

ABSTRACT: The development of Next-Generation Sequencing (NGS) has provided useful diagnostic, prognostic, and therapeutic strategies for individualized management of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients. Consequently, NGS is rapidly being established in clinical practice. However, the technology's complexity, bioinformatics analysis, and the different available options difficult a broad consensus between different laboratories in its daily routine introduction. This collaborative study among Spanish centers was aimed to assess the feasibility, pros, and cons of our customized panel and other commercial alternatives of NGS-targeted approaches. The custom panel was tested in three different sequencing centers. We used the same samples to assess other commercial panels (Oncomine^TM Childhood Cancer Research Assay; Archer^®FusionPlex^® ALL, and Human Comprehensive Cancer Panel GeneRead Panel v2^®). Overall, the panels showed a good performance in different centers and platforms, but each NGS approach presented some issues, as well as pros and cons. Moreover, a previous consensus on the analysis and reporting following international guidelines would be preferable to improve the concordance in results among centers. Our study shows the challenges posed by NGS methodology and the need to consider several aspects of the chosen NGS-targeted approach and reach a consensus before implementing it in daily practice.

SUBMITTER: Vega-Garcia N

PROVIDER: S-EPMC7711852 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Helpful Criteria When Implementing NGS Panels in Childhood Lymphoblastic Leukemia.

Vega-Garcia Nerea N Benito Rocío R Esperanza-Cebollada Elena E Llop Marta M Robledo Cristina C Vicente-Garcés Clara C Alonso Javier J Barragán Eva E Fernández Guerau G Hernández-Sánchez Jesús M JM Martín-Izquierdo Marta M Maynou Joan J Minguela Alfredo A Montaño Adrián A Ortega Margarita M Torrebadell Montserrat M Cervera José J Sánchez Joaquín J Jiménez-Velasco Antonio A Riesco Susana S Hernández-Rivas Jesús M JM Lassaletta Álvaro Á Fernández José María JM Rives Susana S Dapena José Luis JL Ramírez Manuel M Camós Mireia M On Behalf Of The Group Of Leukemia Of The Spanish Society Of Pediatric Hematology And Oncology Sehop

Journal of personalized medicine 20201126 4

The development of Next-Generation Sequencing (NGS) has provided useful diagnostic, prognostic, and therapeutic strategies for individualized management of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients. Consequently, NGS is rapidly being established in clinical practice. However, the technology's complexity, bioinformatics analysis, and the different available options difficult a broad consensus between different laboratories in its daily routine introduction. This collaborati ...[more]

PMID: 33255984

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Project description:Comprehensive studies on neutropenia and infection-related complications in patients with acute lymphoblastic leukemia (ALL) are lacking.We evaluated infection-related complications that were grade??3 on National Cancer Institute's Common Terminology Criteria for Adverse Events (version 3.0) and their risk factors in 409 children with newly diagnosed ALL throughout the treatment period.Of the 2420 infection episodes, febrile neutropenia and clinically or microbiologically documented infection were seen in 1107 and 1313 episodes, respectively. Among documented infection episodes, upper respiratory tract was the most common site (n?=?389), followed by ear (n?=?151), bloodstream (n?=?147), and gastrointestinal tract (n?=?145) infections. These episodes were more common during intensified therapy phases such as remission induction and reinduction, but respiratory and ear infections, presumably viral in origin, also occurred during continuation phases. The 3-year cumulative incidence of infection-related death was low (1.0±0.9%, n?=?4), including 2 from Bacillus cereus bacteremia. There was no fungal infection-related mortality. Age 1-9.9 years at diagnosis was associated with febrile neutropenia (P?=?0.002) during induction and febrile neutropenia and documented infection (both P?<?0.001) during later continuation. White race was associated with documented infection (P?=?0.034) during induction. Compared with low-risk patients, standard- and high-risk patients received more intensive therapy during early continuation and had higher incidences of febrile neutropenia (P?<?0.001) and documented infections (P?=?0.043). Furthermore, poor neutrophil surge after dexamethasone pulses during continuation, which can reflect the poor bone marrow reserve, was associated with infections (P?<?0.001).The incidence of infection-related death was low. However, young age, white race, intensive chemotherapy, and lack of neutrophil surge after dexamethasone treatment were associated with infection-related complications. Close monitoring for prompt administration of antibiotics and modification of chemotherapy should be considered in these patients.

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Helpful Criteria When Implementing NGS Panels in Childhood Lymphoblastic Leukemia.

Publications

Helpful Criteria When Implementing NGS Panels in Childhood Lymphoblastic Leukemia.

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