Dataset Information

Enhanced Risk Stratification for Children and Young Adults with B-Cell Acute Lymphoblastic Leukemia: A Children's Oncology Group Report.

ABSTRACT: Current strategies to treat pediatric acute lymphoblastic leukemia rely on risk stratification algorithms using categorical data. We investigated whether using continuous variables assigned different weights would improve risk stratification. We developed and validated a multivariable Cox model for relapse-free survival (RFS) using information from 21199 patients. We constructed risk groups by identifying cutoffs of the COG Prognostic Index (PI_COG) that maximized discrimination of the predictive model. Patients with higher PI_COG have higher predicted relapse risk. The PI_COG reliably discriminates patients with low vs. high relapse risk. For those with moderate relapse risk using current COG risk classification, the PI_COG identifies subgroups with varying 5-year RFS. Among current COG standard-risk average patients, PI_COG identifies low and intermediate risk groups with 96% and 90% RFS, respectively. Similarly, amongst current COG high-risk patients, PI_COG identifies four groups ranging from 96% to 66% RFS, providing additional discrimination for future treatment stratification. When coupled with traditional algorithms, the novel PI_COG can more accurately risk stratify patients, identifying groups with better outcomes who may benefit from less intensive therapy, and those who have high relapse risk needing innovative approaches for cure.

SUBMITTER: DelRocco NJ

PROVIDER: S-EPMC10997503 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature

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Enhanced Risk Stratification for Children and Young Adults with B-Cell Acute Lymphoblastic Leukemia: A Children's Oncology Group Report.

DelRocco N J NJ Loh M L ML Borowitz M J MJ Gupta S S Rabin K R KR Zweidler-McKay P P Maloney K W KW Mattano L A LA Larsen E E Angiolillo A A Schore R J RJ Burke M J MJ Salzer W L WL Wood B L BL Carroll A J AJ Heerema N A NA Reshmi S C SC Gastier-Foster J M JM Harvey R R Chen I M IM Roberts K G KG Mullighan C G CG Willman C C Winick N N Carroll W L WL Rau R E RE Teachey D T DT Hunger S P SP Raetz E A EA Devidas M M Kairalla J A JA

Leukemia 20240215 4

Current strategies to treat pediatric acute lymphoblastic leukemia rely on risk stratification algorithms using categorical data. We investigated whether using continuous variables assigned different weights would improve risk stratification. We developed and validated a multivariable Cox model for relapse-free survival (RFS) using information from 21199 patients. We constructed risk groups by identifying cutoffs of the COG Prognostic Index (PI<sub>COG</sub>) that maximized discrimination of the ...[more]

PMID: 38360863

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Project description:PurposeSurvival for children and young adults with high-risk B-acute lymphoblastic leukemia has improved significantly, but 20% to 25% of patients are not cured. Children's Oncology Group study AALL0232 tested two interventions to improve survival.Patients and methodsBetween January 2004 and January 2011, AALL0232 enrolled 3,154 participants 1 to 30 years old with newly diagnosed high-risk B-acute lymphoblastic leukemia. By using a 2 × 2 factorial design, 2,914 participants were randomly assigned to receive dexamethasone (14 days) versus prednisone (28 days) during induction and high-dose methotrexate versus Capizzi escalating-dose methotrexate plus pegaspargase during interim maintenance 1.ResultsPlanned interim monitoring showed the superiority of the high-dose methotrexate regimens, which exceeded the predefined boundary and led to cessation of enrollment in January 2011. At that time, participants randomly assigned to high-dose methotrexate during interim maintenance 1 versus those randomly assigned to Capizzi methotrexate had a 5-year event-free survival (EFS) of 82% versus 75.4% (P = .006). Mature final data showed 5-year EFS rates of 79.6% for high-dose methotrexate and 75.2% for Capizzi methotrexate (P = .008). High-dose methotrexate decreased both marrow and CNS recurrences. Patients 1 to 9 years old who received dexamethasone and high-dose methotrexate had a superior outcome compared with those who received the other three regimens (5-year EFS, 91.2% v 83.2%, 80.8%, and 82.1%; P = .015). Older participants derived no benefit from dexamethasone during induction and experienced excess rates of osteonecrosis.ConclusionHigh-dose methotrexate is superior to Capizzi methotrexate for the treatment of high-risk B-acute lymphoblastic leukemia, with no increase in acute toxicity. Dexamethasone given during induction benefited younger children but provided no benefit and was associated with a higher risk of osteonecrosis among participants 10 years and older.

Dataset Information

Enhanced Risk Stratification for Children and Young Adults with B-Cell Acute Lymphoblastic Leukemia: A Children's Oncology Group Report.

Publications

Enhanced Risk Stratification for Children and Young Adults with B-Cell Acute Lymphoblastic Leukemia: A Children's Oncology Group Report.

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