Hassan Seham, Ahmed Sonia, Ali Nesreen, Mokhles Abeer, Zaky Iman, Reda Hala, Youssef Sarah H, Hammad Dina, Hassanain Omneya, Sidhom Iman
Pediatric Oncology Department, Children's Cancer Hospital Egypt, Cairo, Egypt.
Pediatric Oncology Department, National Cancer Institute, Cairo University, and Children's Cancer Hospital Egypt, Cairo, Egypt.
Front Oncol. 2025 Jun 26;15:1606261. doi: 10.3389/fonc.2025.1606261. eCollection 2025.
Asparaginase-associated pancreatitis (AAP) poses a significant challenge in pediatric patients with acute lymphoblastic leukemia (ALL), with its severity ranging from mild cases to potentially life-threatening conditions.
To study the incidence, risk factors of AAP, and its impact on outcome in pediatric ALL patients in a large pediatric oncology hospital in a low-and middle-income country.
This retrospective study included 1804 pediatric patients newly diagnosed with ALL at a single tertiary care center from June 2012 to December 2017. They were treated with ALL protocol adopted from St Jude total study XV including native E. coli L-asparaginase.
Sixty-three (3.5%) patients experienced AAP. Age ≥10 years at diagnosis, initial white blood cell count (WBC) ≥50x10/L, and standard/high-risk treatment regimen were significantly associated with developing AAP. By multivariate analysis, age ≥10 years and high-dose asparaginase regimens remained significant risk factors for AAP. Mild/moderate AAP was reported in 47 (75%) patients without associated mortality, however, 6/16 (37.5%) patients with severe pancreatitis died. Asparaginase was re-challenged in 39/63 (62%) patients of whom 12 patients (30.8%) experienced recurrent AAP without mortality. Patients who were not re-exposed to asparaginase had a relapse rate of 37.5% compared to 23% for those who were re-challenged. The 5-year event-free-survival (EFS) and cumulative incidence of relapse (CIR) were 63.5% and 24.3%; respectively; for patients with AAP compared to 77% and 14.4% for those without AAP (P=0.01, P=0.02; respectively). However, AAP lost its significant impact when adjusted to other factors including age, WBC, immunophenotype, and ALL risk stratification (EFS: HR1.32; 95%CI, 0.88-1.98; P=0.17 and CIR: HR1.44; 95%CI, 0.86-2.4; .16).
Older age and high-dose asparaginase regimens are independent risk factors of AAP. The decision to re-challenge asparaginase should be carefully considered balancing the risk of recurrent pancreatitis against the potential risk of leukemic relapse.
天冬酰胺酶相关性胰腺炎（AAP）给急性淋巴细胞白血病（ALL）患儿带来了重大挑战，其严重程度从轻度病例到可能危及生命的情况不等。
研究低收入和中等收入国家一家大型儿科肿瘤医院中ALL患儿AAP的发病率、危险因素及其对预后的影响。
这项回顾性研究纳入了2012年6月至2017年12月在一家三级医疗中心新诊断为ALL的1804例儿科患者。他们接受了采用圣裘德总研究XV的ALL方案治疗，包括天然大肠杆菌L-天冬酰胺酶。
63例（3.5%）患者发生了AAP。诊断时年龄≥10岁、初始白细胞计数（WBC）≥50×10⁹/L以及标准/高风险治疗方案与发生AAP显著相关。多因素分析显示，年龄≥10岁和高剂量天冬酰胺酶方案仍是AAP的显著危险因素。47例（75%）患者报告为轻度/中度AAP，无相关死亡病例，然而，16例严重胰腺炎患者中有6例（37.5%）死亡。63例患者中有39例（62%）再次接受天冬酰胺酶治疗，其中12例（30.8%）发生复发性AAP，无死亡病例。未再次接触天冬酰胺酶的患者复发率为37.5%，而再次接受治疗的患者复发率为23%。AAP患者的5年无事件生存率（EFS）和累积复发率（CIR）分别为63.5%和24.3%；无AAP患者分别为77%和14.4%（P = 0.01，P = 0.02）。然而，在对年龄、WBC、免疫表型和ALL风险分层等其他因素进行调整后，AAP失去了显著影响（EFS：HR 1.32；95%CI，0.88 - 1.98；P = 0.17；CIR：HR 1.44；95%CI，0.86 - 2.4；P = 0.16）。
年龄较大和高剂量天冬酰胺酶方案是AAP的独立危险因素。再次使用天冬酰胺酶的决定应谨慎考虑，权衡复发性胰腺炎的风险与白血病复发的潜在风险。
