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Published on: May 10, 2017
Outcomes in patients with ETV6::RUNX1 or high-hyperdiploid B-ALL treated in the St. Jude Total Therapy XV/XVI studies
Katelyn Purvis1, Yinmei Zhou2, Seth E Karol1
1Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN.
Insights
Children with ETV6::RUNX1 or high-hyperdiploid B-cell acute lymphoblastic leukemia (B-ALL) have excellent outcomes with St. Jude low-risk therapy, even for those classified as NCI high-risk. This approach reduces toxicities like thrombosis and pancreatitis.
Area of Science:
- Pediatric Oncology
- Hematology
- Genetics
Background:
- ETV6::RUNX1 and high-hyperdiploid are favorable genetic subtypes of B-cell acute lymphoblastic leukemia (B-ALL) in children.
- The St. Jude (SJ) classification categorizes these B-ALL patients as low risk, often irrespective of National Cancer Institute (NCI) risk stratification.
- Exceptions include slow minimal residual disease (MRD) response or central nervous system/testicular involvement.
Purpose of the Study:
- To analyze the outcomes of children with ETV6::RUNX1 or high-hyperdiploid B-ALL treated within the SJ Total XV/XVI studies (2000-2017).
- To compare event-free survival (EFS) based on SJ and NCI risk classifications and treatment intensities.
- To assess the incidence of toxicities, such as thrombosis and pancreatitis, in relation to treatment intensity.
Main Methods:
- Retrospective analysis of pediatric patients (aged 1-18.99 years) with ETV6::RUNX1 (n=222) or high-hyperdiploid (n=296) B-ALL.
- Stratification of patients based on SJ and NCI risk classifications and treatment regimens (low-risk vs. standard/high-risk).
- Evaluation of 5-year EFS and incidence of specific adverse events.
Main Results:
- Both ETV6::RUNX1 and high-hyperdiploid B-ALL showed high 5-year EFS rates (97.7% and 94.7%, respectively).
- NCI high-risk patients with ETV6::RUNX1 or high-hyperdiploid B-ALL receiving SJ low-risk therapy achieved excellent EFS comparable to standard-risk patients.
- SJ low-risk therapy in NCI high-risk patients was associated with significantly lower rates of thrombosis and pancreatitis compared to standard/high-risk therapy.
Conclusions:
- SJ low-risk therapy provides excellent outcomes and reduced toxicity for pediatric B-ALL patients with ETV6::RUNX1 or high-hyperdiploid genotypes, including those classified as NCI high-risk.
- MRD-directed therapy is effective, but NCI high-risk high-hyperdiploid B-ALL with slow MRD response may need novel therapeutic strategies.
- A significant proportion of NCI high-risk patients with these favorable genotypes benefit from low-intensity treatment regimens.
Abstract:
Children with ETV6::RUNX1 or high-hyperdiploid B-cell acute lymphoblastic leukemia (B-ALL) have favorable outcomes. The St. Jude (SJ) classification considers these patients low risk, regardless of their National Cancer Institute (NCI) risk classification, except when there is slow minimal residual disease (MRD) response or central nervous system/testicular involvement. We analyzed outcomes in children (aged 1-18.99 years) with these genotypes in the SJ Total XV/XVI studies (2000-2017). Patients with ETV6::RUNX1 (n = 222) or high-hyperdiploid (n = 296) B-ALL had 5-year event-free survival (EFS) of 97.7% ± 1.1% and 94.7% ± 1.4%, respectively. For ETV6::RUNX1, EFS was comparable between NCI standard-risk and high-risk patients and between SJ low-risk and standard-risk patients. Of the 40 NCI high-risk patients, 37 who received SJ low-risk therapy had excellent EFS (97.3% ± 2.8%). For high-hyperdiploid B-ALL, NCI high-risk patients had worse EFS than standard-risk patients (87.6% ± 4.5% vs 96.4% ± 1.3%; P = .016). EFS was similar for NCI standard-risk and high-risk patients classified as SJ low risk (96.0% ± 1.5% and 96.9% ± 3.2%; P = .719). However, EFS was worse for NCI high-risk patients than for NCI standard-risk patients receiving SJ standard/high-risk therapy (77.4% ± 8.2% vs 98.0% ± 2.2%; P = .004). NCI high-risk patients with ETV6::RUNX1 or high-hyperdiploid B-ALL who received SJ low-risk therapy had lower incidences of thrombosis (P = .013) and pancreatitis (P = .011) than those who received SJ standard/high-risk therapy. MRD-directed therapy yielded excellent outcomes, except for NCI high-risk high-hyperdiploid B-ALL patients with slow MRD response, who require new treatment approaches. Among NCI high-risk patients, 93% with ETV6::RUNX1 and 54% with high-hyperdiploid B-ALL experienced excellent outcomes with a low-intensity regimen. These trials were registered at www.clinicaltrials.gov as #NCT00137111 and #NCT00549848.
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