Conservative treatment of L-asparaginase-associated lipid abnormalities in children with acute lymphoblastic leukemia.
OBJECTIVE
To determine the incidence and clinical consequences of asparaginase-associated lipid abnormalities in children with acute lymphoblastic leukemia (ALL).


METHODS
Sixty-five newly diagnosed children and adolescents aged 0.4-21 years with ALL or lymphoblastic lymphoma were retrospectively evaluated for lipid abnormalities. They were treated according to the ALLIC-BFM 2002 protocol between 2002 and 2005. Fasting cholesterol levels were measured in all patients and triglycerides (TG) in 42/65 patients.


RESULTS
Prior to treatment, mean cholesterol level was 149 +/- 50 mg/dl, and increased to maximal level 274 +/- 124 mg/dl during treatment. Mean TG level during treatment was 459 +/- 526 mg/dl (range 54-3,009). Twelve patients (28%) had TG levels <200 mg/dl, 18 (43%) had 200-400 mg/dl, 3 (7%) had 400-600 mg/dl, 4 (10%) between 600 and 1,000 mg/dl, and 5 (12%) patients had >1,000 mg/dl. No association was found between TG levels and age or gender. One of the 12 patients with TG >400 mg/dl developed left saggital sinus thrombosis and left frontal lobe infarct. TG level at the time of the event was 2,640 mg/dl. None of the five patients with TG levels >1,000 mg/dl developed pancreatitis. Children with TG levels between 400 and 600 mg/dl were treated by fasting. Fibrates and heparin were added to those with levels >600 mg/dl. Lipid abnormalities normalized in all children upon completion of asparaginase treatment.


CONCLUSIONS
Abnormalities of lipid profile in children with ALL during asparaginase therapy are relatively common. We recommend measuring TG before and during asparaginase treatment. Initiation of conservative treatment could prevent further increase of TG and decrease the risk of potential complications.
Cohen
Hofit
H
The Bert W. Strassburger Lipid Center, Sheba Medical Center, Tel-Hashomer, Israel. hofit.cohen@sheba.health.gov.il
Bielorai
Bella
B
Harats
Dror
D
Toren
Amos
A
Pinhas-Hamiel
Orit
O
D000293:Adolescent; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001215:Asparaginase / Q000008:administration & dosage / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D002995:Clofibric Acid / Q000008:administration & dosage; D050528:Diet, Carbohydrate-Restricted; D018752:Diet, Fat-Restricted; D016903:Drug Monitoring; D005215:Fasting; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000139:chemically induced / Q000208:ethnology / Q000517:prevention & control*; D015228:Hypertriglyceridemia / Q000139:chemically induced / Q000208:ethnology / Q000517:prevention & control*; D000960:Hypolipidemic Agents / Q000008:administration & dosage; D007223:Infant; D007557:Israel / Q000453:epidemiology; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000188:drug therapy* / Q000208:ethnology; D012074:Remission Induction; D012189:Retrospective Studies; D055815:Young Adult
D000970:Antineoplastic Agents; D000960:Hypolipidemic Agents; D002995:Clofibric Acid; D001215:Asparaginase