Obesity and risk for venous thromboembolism from contemporary therapy for pediatric acute lymphoblastic leukemia

Prasca, Saskia; Carmona, Roxana; Ji, Lingyun; Ko, Richard H.; Bhojwani, Deepa; Rawlins, Yasmin; Mittelman, Steven D.; Orgel, Etan

doi:10.1016/j.thromres.2018.02.150

Cited by 14 publications

(14 citation statements)

References 45 publications

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“…6 The induction therapy in our patient included L-asparaginase and corticosteroids, and chemotherapy was the primary risk factor in our patient regarding developing CVST during leukemia treatment. A previous study found that obesity was strongly associated with venous thrombosis, 7 and our patient was obese. Another study reported that some patients represented with neurological symptoms and developed CVST 24 days after head injury.…”

Section: Discussionsupporting

confidence: 64%

Cerebral venous sinus thrombosis in a young child with acute lymphoblastic leukemia: a case report and literature review

et al. 2021

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Acute lymphoblastic leukemia (ALL) is a hematological malignancy. There are many risk factors for thrombus development in patients with ALL, and thrombi may develop in different parts of the body. Cerebral venous sinus thrombosis (CVST) is a rare complication of ALL that usually appears during treatment. We present a patient who developed CVST twice, once before diagnosis and once after treatment for ALL. We also reviewed the literature describing ALL and CVST.

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Section: Discussionsupporting

confidence: 64%

Cerebral venous sinus thrombosis in a young child with acute lymphoblastic leukemia: a case report and literature review

et al. 2021

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“…16 In this study, most increased risk of TE in ALL. [18][19][20][21][22] In our study, older age was associated with a higher risk of PE. We also observed a greater proportion of male sex in patients with PE.…”

Section: Discussionsupporting

confidence: 56%

“…Asparaginase decreases anticoagulant, procoagulant, and fibrinolytic protein levels, especially reduction in antithrombin results in hypercoagulability and increased risk of thrombosis 17 . Exposure to asparaginase, increasing age, T‐cell leukemia, mediastinal mass, obesity, and use of dexamethasone in induction have previously been pointed out as possible factors for increased risk of TE in ALL 18‐22 . In our study, older age was associated with a higher risk of PE.…”

Section: Discussionsupporting

confidence: 56%

“…16,23 To date, no other studies have focused on PE in pediatric and young adult ALL; thus, our finding needs to be confirmed and should be interpreted with caution due to few observations and limited statistical power in our study. In a study by Prasca et al, 22 obesity was a significant risk factor to DVT in children with ALL. A tendency toward an association between increased BMI and PE was observed, although not statistically significant.…”

Section: Discussionmentioning

confidence: 90%

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

Tuckuviene

Bjerg

Jónsson

et al. 2020

Research and Practice in Thrombosis and Haemostasis

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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.

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“…Obesity and metabolic dysfunction play a major role in survivors of childhood ALL leading to increased risk of morbidity and mortality throughout their life [3][4][5][6]. Altered lipid metabolism caused by intensive therapy has been addressed [7][8][9][10][11] and contradictory associations to toxicities such as thromboembolism [12][13][14][15], osteonecrosis [16,17] and pancreatitis [18][19][20][21][22][23][24] have been reported. Furthermore, abnormal lipid levels prior to ALL therapy [25][26][27][28][29] and obesity at time of ALL-diagnosis have been associated with reduced efficacy of induction therapy, impaired event-free and overall survival [30][31][32] as well as suggested as a part of the leukomogenisis [33].…”

Section: Introductionmentioning

confidence: 99%

Dyslipidemia at diagnosis of childhood acute lymphoblastic leukemia

et al. 2020

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As survival of acute lymphoblastic leukemia (ALL) exceeds 90%, limiting therapy-related toxicity has become a key challenge. Cardio-metabolic dysfunction is a challenge during and after childhood ALL therapy. In a single center study, we measured triglycerides (TG), total cholesterol (TC), high (HDL) and low density lipoproteins (LDL) levels at diagnosis and assessed the association with BMI, early therapy response, on-therapy hyperlipidemia and the toxicities; thromboembolism, osteonecrosis and pancreatitis. We included 127 children (1.0-17.9 years) all treated according to the NOPHO ALL2008 protocol. Dyslipidemia was identified at ALL-diagnosis in 99% of the patients, dominated by reduced HDL levels (98%) and mild hypertriglyceridemia (61%). Hypertriglyceridemia was not associated with body mass index (P = 0.71). Five percent of patients had mild hypercholesterolemia, 14% had mild hypocholesterolemia, 13% had decreased and 1% elevated LDL-levels. Increased TG and TC levels at ALL-diagnosis were not associated with any on-therapy lipid levels. Lipid levels and BMI were not associated to MRD after induction therapy; However, BMI and hypercholesterolemia were associated with worse risk group stratification (P<0.045 for all). The cumulative incidence of thromboembolism was increased both for patients with hypo-(20.0%) and hypercholesterolemia (16.7%) compared to patients with normal TC levels (2.2%) at diagnosis (P = 0.0074). In conclusion, dyslipidemic changes were present prior to ALL-therapy in children with ALL but did not seem to affect dysmetabolic traits during therapy and were not predictive of on-therapy toxicities apart from an association between dyscholesterolemia at time of ALL-diagnosis and risk of thromboembolism. However, the latter should be interpreted with caution due to low number in the groups.

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Obesity and risk for venous thromboembolism from contemporary therapy for pediatric acute lymphoblastic leukemia

Cited by 14 publications

References 45 publications

Cerebral venous sinus thrombosis in a young child with acute lymphoblastic leukemia: a case report and literature review

Cerebral venous sinus thrombosis in a young child with acute lymphoblastic leukemia: a case report and literature review

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

Dyslipidemia at diagnosis of childhood acute lymphoblastic leukemia

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