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DNA index as prognostic factor in childhood acute lymphoblastic leukemia in the COG-TARGET database
Kun-Yin Qiu1,2, Xiong-Yu Liao1,2, Zhan-Wen He1,2
1Department of Paediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, People's Republic of China.
Insights
DNA index (DI) between 1.1 and 1.2 is a favorable prognostic factor in pediatric acute lymphoblastic leukemia (ALL). This finding aids in risk stratification for better treatment outcomes in childhood ALL.
Area of Science:
- Oncology
- Pediatric Hematology
- Genetics
Background:
- Pediatric acute lymphoblastic leukemia (ALL) treatment outcomes vary significantly.
- Identifying reliable prognostic markers is crucial for optimizing therapy in childhood ALL.
- The DNA index (DI) has been investigated as a potential prognostic indicator.
Purpose of the Study:
- To evaluate the prognostic value of the DNA index (DI) in pediatric ALL patients treated on Children's Oncology Group (COG) protocols.
- To determine if DI can serve as a significant cut-point for risk stratification.
- To correlate DI with event-free survival (EFS) and overall survival (OS).
Main Methods:
- Retrospective analysis of 1668 pediatric ALL patients from the TARGET dataset (2000-2015).
- Evaluation of DNA index (DI) and its association with EFS and OS.
- Multivariate analysis and generalized additive models were employed to assess prognostic significance.
Main Results:
- The study included 1668 pediatric ALL patients with a median follow-up of 7.7 years.
- ETV6/RUNX1 fusion gene was associated with better EFS and OS, while bone marrow non-relapse (BM NR) on Day 29 indicated poorer outcomes.
- Multivariate analysis confirmed DI as a significant prognostic factor, with a DI between 1.1 and 1.2 associated with the most favorable outcomes.
Conclusions:
- The DNA index (DI) between 1.1 and 1.2 is a significant favorable prognostic factor in pediatric ALL.
- ETV6/RUNX1 fusion and BM NR on Day 29 are also critical prognostic indicators in childhood ALL.
- These findings support the use of DI for risk stratification in pediatric ALL treatment protocols.
Background:
This study was aimed to evaluate the value of DNA index(DI) among pediatric acute lymphoblastic leukemia (ALL) treated on Children's Oncology Group (COG) protocols between 2000 and 2015.
Methods:
Retrospective study were analysis among pediatric ALL patients from the TARGET dataset.
Result:
Totally, 1668 eligible pediatric patients were enrolled in this study. Of them, 993 are male and 675 are female with a median age of 7.6 years old. The median follow-up for those patients was 7.7 years (range 0.1-15.7 years). The probability of 15-year EFS and OS were reported to be 67.5 ± 3.1% and 78.3 ± 2.5%, respectively. BCR/ABL1 fusion gene affected the early treatment response and the survival of childhood ALL. Moreover, those patients with ETV6/RUNX1 fusion gene were also significantly associated with better EFS (HR = 0.6, 95% CI 0.4-0.8, P = 0.003) and OS (HR = 0.3, 95%CI 0.2-0.5, P < 0.001) compared to patients with no ETV6/RUNX1. On the contrary, BM NR on Day+ 29 showed a significant decrease in EFS (HR = 3.1, 95%CI 2.1-4.5, P < 0.001) and OS (HR = 1.7, 95%CI 1.1-2.8, P = 0.026). Multivariate analysis showed that DI was significantly associated with better EFS and OS. The threshold effect of DI on poor outcome was significant after adjusting for potential confounders. The adjusted regression coefficient (Log RR) was 0.7 (95%CI 0.1-3.2, P = 0.597) for DI < 1.1 while 8.8 (95%CI 1.4-56.0, P = 0.021) for DI ≥ 1.2 and 0.0 (95%CI 0.0-0.8, P = 0.041) for 1.1 ≤ DI < 1.2. Generalized additive models revealed that the lowest rates of the adverse outcomes estimated to occur among DI between 1.1 and 1.2.
Conclusion:
For those childhood ALL treated on COG protocols between 2000 and 2015, ETV6/RUNX1 and BM NR were closely related to the prognosis. Moreover, the DI between 1.1 and 1.2 can serve as a significant cut-point discriminating the risk group, which indicated a favourable prognostic factor.
