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Researchers characterized the prognostic significance of several forms of hyperdiploidy in acute lymphoblastic leukemia (ALL).
They also identified differences in sensitivity to cytotoxic agents based on particular chromosomal patterns. Results of the study were published in the Journal of Clinical Oncology.
The researchers conducting the study evaluated outcomes for children and adolescents with ALL who received 2 consecutive regimens for frontline treatment at St Jude Children’s Research Hospital, with outcomes considered based on hyperdiploid status in patients with B-cell ALL (B-ALL).
Hyperdiploidy was considered using multiple possible definitions, each of which was compared for prognostic value. These definitions included:
- Chromosome count of 51 to 67
- DNA index (DI)-based hyperdiploidy, with DI being a measure of the ratio of DNA content in leukemic G0/G1 cells compared with normal diploid cells and hyperdiploidy marked by a DI of ≥1.16 to <1.6 (DI1.16-1.6)
- United Kingdom ALL study group low-risk hyperdiploid status, involving simultaneous trisomy of chromosomes 17 and 18 or +17 or +18 without +5 and +20
- Single trisomy of chromosome 18
- Double trisomy of chromosomes 4 and 10
- Triple trisomy (TT) of chromosomes 4, 10, and 17
To identify potential differences in sensitivities to cytotoxic agents, the researchers also performed pharmacotyping of primary ALL cells from a subset of patients.
There were 1096 patients with ALL included in the study, of whom 915 had B-ALL. Pharmacotyping was conducted using data from 634 patients, among whom 526 patients had B-ALL, and 26.7% of these patients with B-ALL had hyperdiploidy.
A univariate analysis of hyperdiploidy definitions and outcomes suggested that TT was most favorable for event-free survival (EFS) and cumulative incidence of relapse (CIR). In this univariate analysis, patients with TT had a 10-year EFS rate of 97.3%, compared with 86.8% for other patients with B-ALL (P =.0003).
The 10-year CIR for patients with TT was 1.4%, compared with 8.8% for other patients with B-ALL (P =.002) in this analysis. To account for additional clinical prognostic factors, the researchers also performed a multivariable analysis of hyperdiploidy and outcomes.
In this analysis, DI1.16-1.6 emerged as the measure of hyperdiploidy associated with the most favorable EFS and CIR outcomes, with a hazard ratio (HR) of 0.45 (95% CI, 0.23-0.88; P =.02) for EFS and an HR of 0.45 (95% CI, 0.21-0.99; P =.046) for CIR.
In the pharmacotyping analysis, among patients with B-ALL, those having DI1.16-1.6 hyperdiploid status showed the greatest sensitivity to cytarabine (P =.008) and to asparaginase (P =.025) in comparisons with other patients. Greater asparaginase sensitivity also was observed with trisomy of chromosomes 16 and 17, while asparaginase resistance was associated with gains in chromosomes 7 and 9. Mercaptopurine sensitivity appeared greater with gains in chromosomes 14 and 17.
“Overall, our results suggest that DI may be the most optimal definition of hyperdiploidy because it identifies a sufficiently large group with excellent prognosis, achieving maximal impact by balancing patient numbers and favorable outcomes,” the researchers wrote in their report.
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of disclosures.
Reference
Lee SHR, Ashcraft E, Yang W, et al. Prognostic and pharmacotypic heterogeneity of hyperdiploidy in childhood ALL. J Clin Oncol. Published online September 20, 2023. doi:10.1200/JCO.23.00880
This article originally appeared on Hematology Advisor
