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

Abstract

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.

Keywords

• acute lymphoblastic leukemia
• asparaginase
• incidence
• pulmonary embolism
• toxicity