Cancer Res Treat.  2025 Apr;57(2):558-569. 10.4143/crt.2024.127.

Survival of Children with Acute Lymphoblastic Leukemia with Risk Group–Based Protocol Changes: A Single-Center Experience with 460 Patients over a 20-Year Period

• Lee NH
• Ju HY
• Yi ES
• Choi YB
• Yoo KH
• Koo HH

• KMID: 2566872
• DOI: http://doi.org/10.4143/crt.2024.127

Abstract

Purpose
Recent treatments for pediatric acute lymphoblastic leukemia (ALL) are founded on risk stratification. We examined the survival rates and prognostic factors of patients over a 20-year period at a single institution.
Materials and Methods
This study analyzed patients diagnosed with ALL and treated at the Pediatric Department of Samsung Medical Center (SMC). Patients were categorized into standard-risk (SR), high-risk (HR), and very high-risk (VHR) groups. The SMC protocol for the HR group underwent two changes during the study period: a modified Children’s Cancer Group (CCG)-1882 protocol was used from 2000 to 2005, the Korean multicenter HR ALL-0601 protocol from 2006 to 2014, and the Korean multicenter HR ALL-1501 protocol from 2015 to 2019.
Results
Of the 460 patients, complete remission was achieved in 436 patients (94.8%). The 10-year overall survival rate (OS) was 83.8±1.9% for all patients. OS according to the SMC risk group was as follows: 95.9%±1.4% in the SR group, 83.8%±3.6% in the HR group, and 66.2%±6.9% in the VHR group. The 5-year OS within the HR group varied according to the treatment protocol: 73.9%±7.5%, in the modified CCG-1882 protocol, 83.0%±3.9%, in the 0601 protocol, and 96.2%±2.6%, in the 1501 protocol. For those aged 15 years and older, the OS was only 56.5%±13.1%. Relapse occurred in 71 patients (15.4%), and the OS after relapse was 37.7%±6.0%.
Conclusion
The treatment outcomes of patients with ALL improved markedly. However, there is a need to further characterize adolescents and young adult patients, as well as those who have experienced relapses.

Keyword

Acute lymphoblastic leukemia; Pediatrics; Risk factors; Prognosis

Figure

• 

  Fig. 1. Change of treatment scheme of acute lymphoblastic leukemia (ALL) in Samsung Medical Center (SMC). In the standard-risk group, a modified Children’s Cancer Group (CCG)-1891 protocol, involving remission induction using prednisolone, L-asparaginase, and vincristine with intrathecal chemotherapy, was consistently applied throughout the entire study period [9]. In contrast, the treatment protocol for the high-risk group underwent two modifications. Initially, from 2000 to 2005, a modified CCG-1882 protocol was employed [10]. Subsequently, from 2006 to 2014, the Korean multicenter high-risk ALL-0601 protocol was utilized. Finally, from 2015 to 2019, the Korean multicenter high-risk ALL-1501 protocol was implemented. Allogeneic hematopoietic stem cell transplantation was performed after the third cycle of consolidation following remission induction in the very high-risk group. HSCT, hematopoietic stem transplantation; RER, rapid early responder; SER, slow early responders; VHR, very high-risk.

• 

  Fig. 2. Survival rates of total patients. (A) The 10-year overall survival rate for all patients was 83.8%±1.9%. (B) The 10-year relapse-free survival rate for all patients was 77.3%±2.1%. (C) The 10-year cumulative incidence of relapse for all patients was 17.3%±2.0%. (D) The 10-year treatment related mortality rate in all patients was 9.0%±1.5%.

• 

  Fig. 3. Survival rates according to clinical factors. (A) The 10-year overall survival (OS) exhibited variation by age, with rates of 64.6%±10.8% for children under 1 year, 89.4%±1.8% for those aged 1 to 10 years, and 72.6%±4.5% for those aged 10 years or older, demonstrating a significant difference (p < 0.001). Notably, individuals aged 15 years or older had a very poor prognosis, with an OS of 56.5%±13.1%. (B, C) According to the National Cancer Institute (NCI) risk group, the 10-year OS was 92.4% for the standard-risk (SR) group and 73.1% in the high-risk (HR) group (p < 0.001). According to the Samsung Medical Center (SMC) risk group, it was 95.5%±1.4% in the SR group, 83.8%±3.6% for the HR group, and 66.2%±6.9% for the very high-risk group (p < 0.001). (D) The 10-year OS for specific cytogenetic abnormalities included 66.7%±13.6% for t(4;11), 58.0%±7.9% for the Philadelphia chromosome, 33.3%±27.2% for hypodiploidy, 81.2%±3.6% for normal chromosomes, 90.7%±3.7% for ETV6::RUNX1, and 93.1%±3.6% for hyperdiploidy (p < 0.001). VHR, very high-risk.

• 

  Fig. 4. Survival rates according to treatment protocols. (A) The 5-year overall survival for the modified Children’s Cancer Group (CCG)-1891 protocol in the standard-risk group was 96.8%±1.3%, while for the high-risk (HR) group protocols, it was 73.9%±7.5% for the modified CCG-1882 protocol, 83.0%±3.9% for the 0601 protocol, and 96.2%±2.6% for the 1501 protocol (p < 0.001). (B) Among HR patients, 5-year overall survival was 93.1%±3.8% in the rapid early responder (RER) and 94.9%±3.6% in the slow early responder (SER) groups, respectively (p=0.264).

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  Fig. 5. Survival rates of relapse patients. (A) The 5-year overall survival for relapsed patients was 37.7%±6.0%. (B) Within the relapsed patients, the 5-year overall survival for the group experiencing relapse after 60 months was 71.3%±14.1%, while for the group relapsing before 60 months, it was 31.5%±6.3% (p=0.05).

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