Thrombosis is associated with worse survival in children with acute lymphoblastic leukemia: A report from CYP‐C

Abstract

There are conflicting data about whether the development of cancer‐associated thrombo‐embolism (TE) negatively impacts survival in children. The objective was to determine whether TE during treatment was associated with overall survival (OS) and event‐free survival (EFS) in children with acute lymphoblastic leukemia (ALL). We performed a population‐based retrospective cohort study using the Cancer in Young People‐Canada registry. Children <15 years of age were diagnosed with de novo ALL (2000–2016). The primary exposure variable was radiologically‐confirmed thrombo‐embolism requiring medical intervention. Multivariable Cox regression models were used to determine the impact of thrombo‐embolism on survival, where TE was time‐dependent. We included 2006 children (median age: 4 years, 88.5% precursor B‐cell ALL). Thrombo‐embolism occurred in 113 patients (5.6%), at a median time of 107 days (interquartile range: 35–184 days) after ALL diagnosis. Among standard/low‐risk patients, 41/1165 (3.5%) developed TE while among high/very high‐risk patients, 72/841 (8.6%) developed TE. Patients with TE had a significantly worse OS (adjusted HR [aHR] of death: 2.61, 95% CI: 1.62–4.22, p < 0.001) and EFS (aHR of an event [death, relapse, second malignancy]: 2.03, 95% CI: 1.35–3.05, p = 0.001), compared with patients without TE. No statistically significant difference was seen in standard/low risk ALL for OS and EFS, but TE was associated with a significantly lower OS and EFS in children with high/very high‐risk ALL (aHR of death: 2.90, 95% CI: 1.79–4.72, p < 0.001; aHR of an event: 2.02, 95% CI: 1.30–3.12, p = 0.002). Thus, TE led to a statistically significant reduction in OS and EFS in children with high risk/very high‐risk leukemia.

Thrombosis Complications in Pediatric Acute Lymphoblastic Leukemia: Risk Factors, Management, and Prevention: Is There Any Role for Pharmacologic Prophylaxis?

“…Conflicting data exists whether the development of cancer associated VTE has a negative impact on survival. In a population-based retrospective cohort study using the “Cancer in Young People Canada Registry”, 2006 children < 15 years of age (median age 4 years) with the diagnosis of ALL (88.5% B-cell precursor ALL) were studied for VTE and survival outcomes ( 78 ). Thromboembolism occurred in 113 patients (5.6%) at a median time of 107 days (IQR 35–184) from ALL diagnoses.…”

“…Patients with VTE had worse overall survival with a HRa for death of 2.61 (95% CI 1.62–4.22) p < 0.001) and EFS (HRa of death, relapse, second malignancy: 2.03 95% CI 1.35–3.05 p = 0.001) compared to patients without VTE. Thromboembolism was associated with significantly lower overall survival and event-free survival in children with high/very high-risk ALL (HRa 2.90, 95% CI 1.79–4.72, p < 0.001 and HRa 2.02, 95% CI 1.30–3.12 p = 0.002, respectively) ( 78 ). Omission of asparaginase can result in inferior leukemic survival.…”

Challenges in Management of VTE in Children With Cancer: Risk Factors and Treatment Options

“…Thrombosis occurs in up to 36% of pediatric patients with ALL, many of which occur during induction remission ( 28 ) with a median time of 107 days ( 4 ). A recent study demonstrated an increased risk among high/very high-risk leukemia patients (8.6%) vs. standard/low-risk patients (3.5%) ( 4 ).…”

“…Thrombosis occurs in up to 36% of pediatric patients with ALL, many of which occur during induction remission ( 28 ) with a median time of 107 days ( 4 ). A recent study demonstrated an increased risk among high/very high-risk leukemia patients (8.6%) vs. standard/low-risk patients (3.5%) ( 4 ). Patients with ALL are at particular risk for VTE due to multiple risk factors at diagnosis and throughout induction therapy such as endothelial damage from central venous catheter insertion, the inherent prothrombotic state associated with cancer, as well as pro-thrombotic medications that are administered together during induction therapy including asparaginase, corticosteroids, and anthracyclines ( 8 ).…”

“…Thrombotic complications are well-recognized in children with cancer and can lead to significant morbidity ( 1 – 3 ) and reduced survival ( 4 – 6 ). The incidence greatly exceeds that of the general pediatric population with an incidence of 2.1–16% for symptomatic thrombosis and up to 50% when including asymptomatic events ( 7 – 10 ).…”