Pulmonary embolism in acute lymphoblastic leukemia — An observational study of 1685 patients treated according to the NOPHO ALL2008 protocol

Abstract

Background Pulmonary embolism (PE) is a serious complication of acute lymphoblastic leukemia (ALL). We examined the cumulative incidence and clinical presentation of PE in a well‐defined cohort of patients with ALL aged 1‐45 years treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol. Methods As part of the mandatory toxicity reporting of NOPHO ALL2008, thromboembolism including PE was reported consecutively. The cumulative incidence of first‐time PE was calculated using the Aalen‐Johansen estimator during a 2.5‐year period from ALL diagnosis. We used Fisher’s exact test to examine categorical variables and Cox logistic regression to estimate hazard ratios (HRs) for PE. Results PE was diagnosed in 32 of 1685 patients. The 2.5‐year cumulative incidence of first‐time PE increased with age: 0.43% (95% CI, 0.18‐1.03) in children aged 1‐9 years, 3.28% (95% CI, 1.72‐6.22) in children aged 10‐17 years, and 7.22% (95% CI, 4.61‐11.21) in adults aged 18‐45 years. The majority of PEs, 78% (25/32), occurred during asparaginase treatment. HRs adjusted for age and sex were associated with male sex (HR, 2.4; 95% CI, 1.0‐5.6) and older age (10‐17 years: HR 7.5; 95% CI, 2.5‐22.2), 18‐45 years: HR, 16.5; 95% CI, 6.1‐44.5). In two‐thirds of the patients (63%; 17/27), PE and its treatment had no impact on the administered doses of asparaginase. PE‐associated 30‐day mortality was 9.4% (95% CI, 1.9‐25.0). Conclusions Awareness of PE is warranted during ALL treatment. Larger multicenter studies are needed to examine predictors of PE in ALL.

Predictors of thrombosis in children receiving therapy for acute lymphoblastic leukemia: Results from Dana‐Farber Cancer Institute ALL Consortium trial 05‐001

“…The Nordic Society for Paediatric Haematology and Oncology (NOPHO) studies documented about 9%-10% case fatality rate in children with ALL and TE, highlighting the seriousness of this condition. 7,8 Further, even in the absence of TE-related mortality, recent studies have documented an independent adverse impact of ALL-associated TE on overall or EFS. 6 In our cohort, there was no mortality associated with TE, and in contrast to a report by Pelland-Marcotte et al, there was no difference in OS and EFS in patients with or without TE.…”

“…[1][2][3][4][5] Recent studies have also suggested that TE may adversely impact overall and event-free survival in children with ALLassociated TE. [6][7][8] Anticoagulation prophylaxis is effective in preventing TE in patients at high risk for TE. 9 However, it is associated with increased risk of bleeding especially in patients receiving myelosuppressive therapy.…”

“…Thromboembolism (TE) has been increasingly reported in contemporary clinical trials as a serious complication in children with acute lymphoblastic leukemia (ALL) resulting in significant morbidity and therapy alterations 1–5 . Recent studies have also suggested that TE may adversely impact overall and event‐free survival in children with ALL‐associated TE 6–8 . Anticoagulation prophylaxis is effective in preventing TE in patients at high risk for TE 9 .…”

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

“…Pulmonary embolism (PE) can be a life-threatening complication during ALL therapy. The NOPHO ALL 2008 study reported PE events in 32 of 1,685 patients enrolled in their trial ( 69 ). The 2.5-year cumulative incidence of first-time PE increased with the age groups: 0.43% (95% CI, 0.18–1.03) in children aged 1–9 years, 3.28% (95% CI, 1.72–6.22) in children aged 10–17 years, and 7.22% (95% CI, 4.61–11.21) in adults aged 18–45 years.…”

“…In two-thirds of the patients (63%; 17/27), PE and its treatment had no impact on the cumulative prescribed doses of asparaginase. Their study reported a PE-associated 30-day mortality of 9.4% (95% CI, 1.9–25.0) ( 69 ). Predictive models to assist in the diagnosis of PE need to be further studied in pediatric and young adults with ALL.…”