title: Severe hypertriglyceridaemia during therapy for childhood acute lymphoblastic leukaemia.
abstract: BACKGROUND
  Asparaginase and steroids can cause hypertriglyceridaemia in children with acute lymphoblastic leukaemia (ALL). There are no guidelines for screening or management of patients with severe hypertriglyceridaemia (>1000mg/dL) during ALL therapy.
  
  
  METHODS
  Fasting lipid profiles were obtained prospectively at four time-points for 257 children consecutively enrolled on a frontline ALL study. Risk factors were evaluated by the exact chi-square test. Details of adverse events and management of hypertriglyceridaemia were extracted retrospectively.
  
  
  RESULTS
  Eighteen of 257 (7%) patients developed severe hypertriglyceridaemia. Older age and treatment with higher doses of asparaginase and steroids on the standard/high-risk arm were significant risk factors. Severe hypertriglyceridaemia was not associated with pancreatitis after adjustment for age and treatment arm or with osteonecrosis after adjustment for age. However, patients with severe hypertriglyceridaemia had a 2.5-3 times higher risk of thrombosis compared to patients without, albeit the difference was not statistically significant. Of the 30 episodes of severe hypertriglyceridaemia in 18 patients, seven were managed conservatively while the others with pharmacotherapy. Seventeen of 18 patients continued to receive asparaginase and steroids. Triglyceride levels normalised after completion of ALL therapy in all 12 patients with available measurements.
  
  
  CONCLUSIONS
  Asparaginase- and steroid-induced transient hypertriglyceridaemia can be adequately managed with dietary modifications and close monitoring without altering chemotherapy. Patients with severe hypertriglyceridaemia were not at increased risk of adverse events, with a possible exception of thrombosis. The benefit of pharmacotherapy in decreasing symptoms and potential complications requires further investigation.
authors.affiliation: Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA; Department of Pediatrics, University of Tennessee Health Sciences Center, Memphis, TN, USA. Electronic address: deepa.bhojwani@stjude.org.
authors.forename: Deepa
authors.initials: D
authors.lastname: Bhojwani
authors.affiliation: Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Rashid
authors.initials: R
authors.lastname: Darbandi
authors.affiliation: Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Deqing
authors.initials: D
authors.lastname: Pei
authors.affiliation: Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Laura B
authors.initials: LB
authors.lastname: Ramsey
authors.affiliation: Department of Pediatrics, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Wassim
authors.initials: W
authors.lastname: Chemaitilly
authors.affiliation: Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA; Department of Pediatrics, University of Tennessee Health Sciences Center, Memphis, TN, USA.
authors.forename: John T
authors.initials: JT
authors.lastname: Sandlund
authors.affiliation: Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Cheng
authors.initials: C
authors.lastname: Cheng
authors.affiliation: Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA; Department of Pediatrics, University of Tennessee Health Sciences Center, Memphis, TN, USA.
authors.forename: Ching-Hon
authors.initials: CH
authors.lastname: Pui
authors.affiliation: Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Mary V
authors.initials: MV
authors.lastname: Relling
authors.affiliation: Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA; Department of Pediatrics, University of Tennessee Health Sciences Center, Memphis, TN, USA.
authors.forename: Sima
authors.initials: S
authors.lastname: Jeha
authors.affiliation: Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA; Department of Pediatrics, University of Tennessee Health Sciences Center, Memphis, TN, USA.
authors.forename: Monika L
authors.initials: ML
authors.lastname: Metzger
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001215:Asparaginase / Q000008:administration & dosage / Q000009:adverse effects; D002648:Child; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D005215:Fasting / Q000097:blood; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D015228:Hypertriglyceridemia / Q000139:chemically induced / Q000175:diagnosis*; D008055:Lipids / Q000097:blood; D008297:Male; D010020:Osteonecrosis / Q000139:chemically induced / Q000175:diagnosis; D010195:Pancreatitis / Q000139:chemically induced / Q000175:diagnosis; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D011446:Prospective Studies; D012074:Remission Induction; D018570:Risk Assessment / Q000706:statistics & numerical data; D012307:Risk Factors; D012720:Severity of Illness Index; D013923:Thromboembolism / Q000139:chemically induced / Q000175:diagnosis; D016896:Treatment Outcome
chemical_list: D005938:Glucocorticoids; D008055:Lipids; D011092:Polyethylene Glycols; C042705:pegaspargase; D003907:Dexamethasone; D001215:Asparaginase
keywords: Asparaginase; Childhood ALL; Hypertriglyceridaemia; Thrombosis
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