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Pediatric-inspired protocols in adult acute lymphoblastic leukemia: are the results bearing fruit?

ABSTRACT: Observational findings demonstrating improved survival for younger adults following pediatric, as opposed to adult, acute lymphoblastic leukemia (ALL) regimens have been translated into international, prospective multicenter clinical trials testing the pediatric regimen in young adult ALL. The results of these studies confirm the feasibility of delivering the pediatric regimen in the adult oncology setting and establish the superiority of this approach relative to historical adult cooperative group regimen results. Specific toxicities, including thrombosis, hepatotoxicity, and osteonecrosis, are more prevalent in adults receiving the pediatric regimen relative to young children. Persistent minimal residual disease (MRD) is a strong prognostic indicator in adults receiving the pediatric regimen; sensitive, high-quality MRD evaluation should be performed in all patients receiving these therapies. Incorporation of targeted agents, particularly in the frontline and MRD+ setting, will usher in the next era of the pediatric regimen in adult ALL.

SUBMITTER: Muffly L

PROVIDER: S-EPMC6913493 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Pediatric-inspired protocols in adult acute lymphoblastic leukemia: are the results bearing fruit?

Muffly Lori L Curran Emily E

Hematology. American Society of Hematology. Education Program 20191201 1

Observational findings demonstrating improved survival for younger adults following pediatric, as opposed to adult, acute lymphoblastic leukemia (ALL) regimens have been translated into international, prospective multicenter clinical trials testing the pediatric regimen in young adult ALL. The results of these studies confirm the feasibility of delivering the pediatric regimen in the adult oncology setting and establish the superiority of this approach relative to historical adult cooperative gr ...[more]

PMID: 31808881

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Project description:BackgroundRetrospective studies have shown adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) have superior survival when treated in pediatric versus adult centers (locus of care; LOC). Several adult centers recently adopted pediatric protocols. Whether this has narrowed LOC disparities in real-world settings is unknown.MethodsThe IMPACT Cohort is an Ontario population-based cohort that captured demographic, disease and treatment (treatment protocol, chemotherapy doses) data for all 15-21 year olds diagnosed with ALL 1992-2011. Cancer outcomes were determined by chart abstraction and linkage to provincial healthcare databases. Treatment protocols were classified as pediatric- or adult-based. We examined predictors of outcome, including LOC, protocol, disease biology, and time period.ResultsOf 271 patients, 152 (56%) received therapy at adult centers. 5-year event-free survival (EFS ± SE) among AYA at pediatric vs adult centers was 72% ± 4% vs 56% ± 4% (P = 0.03); 5-year overall survival (OS) was 82% ± 4% vs 64% ± 4% (P < 0.001). After adjustment, OS remained inferior at adult centers (hazard ratio 2.5; 95% confidence interval 1.1-6.1; P = 0.04). In the most recent period (2006-2011), 39/59 (66%) AYA treated at adult centers received pediatric protocols. These AYA had outcomes superior to the 20 AYA treated on adult protocols, but inferior to the 44 AYA treated at pediatric centers (EFS 72% ± 5% vs 60% ± 9% vs 81% ± 6%; P = 0.02; OS 77% ± 7% vs 65% ± 11% vs 91% ± 4%; P = 0.004). Induction deaths and treatment-related mortality did not vary by LOC.ConclusionsSurvival disparities between AYA with ALL treated in pediatric vs adult centers have persisted over time, partially attributable to incomplete adoption of pediatric protocols by adult centers. Although pediatric protocol use has improved survival, residual disparities remain, perhaps due to other differences in care between adult and pediatric centers.

Project description:Differences in survival have been reported between pediatric and adult acute lymphoblastic leukemia. The inferior prognosis in adult acute lymphoblastic leukemia is not fully understood but could be attributed, in part, to differences in genomic alterations found in adult as compared to in pediatric acute lymphoblastic leukemia.We compared two different sets of high-density single nucleotide polymorphism array genotyping data from 75 new diagnostic adult and 399 previously published diagnostic pediatric acute lymphoblastic leukemia samples. The patients' samples were randomly acquired from among Caucasian and Asian populations and hybridized to either Affymetrix 50K or 250K single nucleotide polymorphism arrays. The array data were investigated with Copy Number Analysis for GeneChips (CNAG) software for allele-specific copy number analysis.The high density single nucleotide polymorphism array analysis of 75 samples of adult acute lymphoblastic leukemia led to the identification of numerous cryptic and submicroscopic genomic lesions with a mean of 7.6 genomic alterations per sample. The patterns and frequencies of lesions detected in the adult samples largely reproduced known genomic hallmarks detected in previous single nucleotide polymorphism-array studies of pediatric acute lymphoblastic leukemia, such as common deletions of 3p14.2 (FHIT), 5q33.3 (EBF), 6q, 9p21.3 (CDKN2A/B), 9p13.2 (PAX5), 13q14.2 (RB1) and 17q11.2 (NF1). Some differences between adult and pediatric acute lymphoblastic leukemia were identified when the pediatric data set was partitioned into hyperdiploid and non-hyperdiploid cases and then compared to the nearly exclusively non-hyperdiploid adult samples. In this analysis, adult samples had a higher rate of deletions of chromosome 17p (TP53) and duplication of 17q.Our analysis of adult acute lymphoblastic leukemia cases led to the identification of new potential target lesions relevant for the pathogenesis of acute lymphoblastic leukemia. However, no unequivocal pattern of submicroscopic genomic alterations was found to separate adult acute lymphoblastic leukemia from pediatric acute lymphoblastic leukemia. Therefore, apart from different therapy regimen, differences of prognosis between adult and pediatric acute lymphoblastic leukemia are probably based on genetic subgroups according to cytogenetically detectable lesions but not focal genomic copy number microlesions.

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Pediatric-inspired protocols in adult acute lymphoblastic leukemia: are the results bearing fruit?

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Pediatric-inspired protocols in adult acute lymphoblastic leukemia: are the results bearing fruit?

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