In a study reported in the Journal of Clinical Oncology, O’Connor et al combined genetic subtypes and minimal residual disease as a continuous variable to construct a risk stratification model for pediatric acute lymphoblastic leukemia (ALL).
The study involved a population-based cohort of 3,113 patients treated in a clinical trial (UKALL2003), with a median follow-up of 7 years. Minimal residual disease was evaluated by polymerase chain reaction analysis of Ig/TCR gene rearrangements. Immunophenotype, cytogenetics, and fluorescence in situ hybridization were used to segregate patients into four exclusive genetic subtypes: cytogenetic good, intermediate, and high risk and T-cell acute lymphoblastic leukemia (T-ALL).
Integrated Risk Model
Minimal residual disease value distributions differed according to the distinct genetic subtypes (P < .001). Overall, the risk of relapse was reduced by 20% for each log reduction in minimal residual disease level (hazard ratio = 0.80, P < .001). The risk of relapse was directly proportional to the minimal residual disease level within each genetic risk group, but absolute relapse rates associated with specific minimal residual disease values varied by genetic subtype.
Integrated risk groups were constructed according to the following criteria: standard risk = good-risk cytogenetics and minimal residual disease < 0.1% plus intermediate-risk cytogenetics and minimal residual disease < 0.01% plus T-ALL with undetectable minimal residual disease; intermediate risk = good-risk cytogenetics and minimal residual disease ≥ 0.1% and < 5% plus intermediate-risk cytogenetics and minimal residual disease ≥ 0.01% and < 1% plus T-ALL with minimal residual disease > 0% and < 5%; and high risk = minimal residual disease ≥ 5% plus high-risk cytogenetics plus intermediate-risk cytogenetics and minimal residual disease ≥ 1%. Relapse rates at 5 years were 4%, 13%, and 33% in the three integrated risk groups (P < .001), with 5-year event-free survival of 94%, 83%, and 58% (P < .001), respectively.
The investigators concluded: “A single threshold for assigning patients to a [minimal residual disease] risk group does not reflect the response kinetics of the different genetic subtypes. Future risk algorithms should integrate genetics with [minimal residual disease] to accurately identify patients with the lowest and highest risk of relapse.”
The study was supported by Bloodwise.
Anthony V. Moorman, MD, of Wolfson Childhood Cancer Research Centre, Newcastle University, is the corresponding author of the Journal of Clinical Oncology article.
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