Management of Asparaginase Toxicity in AYAs with ALL

Schmiegelow, Kjeld; Rank, Cecilie Utke

doi:10.1016/s2152-2650(20)30444-4

Cited by 2 publications

(3 citation statements)

References 12 publications

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“…We found that allergic reactions were less common for older children, and this finding is consistent with the study of Schmiegelow and Rank, who showed that the risk of L-asparaginase allergy decreased with age [12].…”

Section: Discussionsupporting

confidence: 92%

“…In recent years, the treatment of ALL in the adolescent and young adult (AYA) age group has been intensively studied, for which chemotherapy protocols involving a high-intensity asparaginase regimen have been shown to lead to better survival [ 10 , 11 ]. Some studies have found a higher risk of pancreatitis and thromboembolism, but not hypersensitivity, in adolescents than in children <10 years [ 12 ], while other studies have reported similar rates of asparaginase-associated toxicity in AYA patients and those <16 years of age [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

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L-Asparaginase Toxicity in the Treatment of Children and Adolescents with Acute Lymphoblastic Leukemia

Schmidt

Ivanov

Coriu

et al. 2021

JCM

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Asparaginase is a basic component of chemotherapy in pediatric acute lymphoblastic leukemia (ALL) and has played a crucial role in improving the long-term survival of this disease. The objectives of this retrospective study were to elucidate the toxicity profile associated with asparaginase in children and adolescents with ALL, to analyze the impact of each type of toxicity on long-term outcomes, and to identify risk factors. We analyzed the medical charts of 165 patients diagnosed with ALL at Sf. Maria Iasi Children’s Hospital from 2010 to 2019 and treated according to a chemotherapeutic protocol containing asparaginase. The median duration of follow-up was 5 years (0.1–11.5 years). Groups of patients with specific types of toxicity were compared to groups of patients without toxicity. We found the following incidence of asparaginase-associated toxicity: 24.1% clinical hypersensitivity, 19.4% hepatotoxicity, 6.7% hypertriglyceridemia, 4.2% hyperglycemia, 3.7% osteonecrosis, 3% pancreatitis, 2.4% thrombosis, and 1.2% cerebral thrombosis. Overall, 82 patients (49.7%) had at least one type of toxicity related to asparaginase. No type of toxicity had a significant impact on overall survival or event-free survival. Being older than 14 years was associated with a higher risk of osteonecrosis (p = 0.015) and hypertriglyceridemia (p = 0.043) and a lower risk of clinical hypersensitivity (p = 0.04). Asparaginase-related toxicity is common and has a varied profile, and its early detection is important for realizing efficient and appropriate management.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

L-Asparaginase Toxicity in the Treatment of Children and Adolescents with Acute Lymphoblastic Leukemia

Schmidt

Ivanov

Coriu

et al. 2021

JCM

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“…In general, the evidence regarding risk factors for hyperlipidemia was conflicting (Table 4). Consistent with asparaginase-associated toxicities such as osteonecrosis, pancreatitis, and thrombosis, 13,[49][50][51] older age (> 10 years) appears to be associated with an increased risk of hyperlipidemia. 14,16,17,27,32 This might be due to more frequent stratification to higher risk groups in older children with more intensive chemotherapy, including asparaginase or related to growth spurts and the onset of puberty.…”

Section: Glucocorticoidsmentioning

confidence: 99%

Hyperlipidemia in children and adolescents with acute lymphoblastic leukemia: A systematic review and meta‐analysis

Laumann,

Pedersen,

Andrés‐Jensen

et al. 2023

Pediatric Blood & Cancer

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BackgroundThe established association between acute lymphoblastic leukemia (ALL) and hyperlipidemia has, in some studies, been linked to toxicities such as pancreatitis, thrombosis, and osteonecrosis. However, a systematic review investigating the incidence, management, and clinical implications of hyperlipidemia during childhood ALL treatment is lacking.ObjectivesSystematically assess the incidence of hyperlipidemia during ALL treatment, explore associations with risk factors and severe toxicities (osteonecrosis, thrombosis, and pancreatitis), and review prevalent management strategies.MethodsA systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) statement. Data synthesis was descriptive, and a meta‐analysis of hypertriglyceridemia and risk of severe toxicities was performed.ResultsWe included 13 studies with 3,425 patients. Hyperlipidemia incidence varied widely (6.7%‐85%) but with inconsistent definitions and screening strategies across studies. Evidence regarding risk factors was conflicting, but age (> 10 years) and treatment with asparaginase and glucocorticosteroids seem to be associated with hyperlipidemia. Hypertriglyceridemia (grade 3/4) increased the risk for osteonecrosis (odds ratio (OR): 4.27, 95% confidence interval (CI): 2.77‐6.61). No association could be established for pancreatitis (OR: 1.60, 95% CI: 0.53‐4.82) or thrombosis (OR: 2.45, 95% CI: 0.86‐7.01), but larger studies are needed to confirm this.ConclusionThe overall evidence of this systematic review is limited by the small number of studies and risk of bias. Our review suggests that hypertriglyceridemia increases the risk for osteonecrosis. However, larger studies are needed to explore the clinical implications of hyperlipidemia and randomized trials investigating hyperlipidemia management and its impact on severe toxicities.

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Management of Asparaginase Toxicity in AYAs with ALL

Cited by 2 publications

References 12 publications

L-Asparaginase Toxicity in the Treatment of Children and Adolescents with Acute Lymphoblastic Leukemia

L-Asparaginase Toxicity in the Treatment of Children and Adolescents with Acute Lymphoblastic Leukemia

Hyperlipidemia in children and adolescents with acute lymphoblastic leukemia: A systematic review and meta‐analysis

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