Individualized Asparaginase Dosing in Childhood Acute Lymphoblastic Leukemia

• DOI: 10.1200/jco.19.02292
• Publication Date: 2020-01-10T20:57:47Z
• Authors: Robin Q.H. Kloos; Rob Pieters; Florine M.V. Jumelet; Hester A. de Groo...; Cor van den Bos; Inge M. van der S...
• Keywords: Asparaginase; Transaminase

PURPOSE In the DCOG ALL-11 protocol, polyethylene glycol–conjugated Escherichia coli asparaginase (PEGasparaginase) and Erwinia treatment of pediatric acute lymphoblastic leukemia are individualized with therapeutic drug monitoring (TDM). The efficacy TDM its effect on asparaginase-associated toxicity reported. PATIENTS AND METHODS After induction 3 fixed intravenous doses 1,500 IU/m 2 PEGasparaginase, medium-risk patients (n = 243) received 14 that targeted trough levels 100-250 IU/L, standard-risk 108) 1 dose, high-risk 18) 2-5 administrations (1,500 ). a neutralizing hypersensitivity reaction, were started 20,000 times per week, l-asparagine was measured to monitor efficacy. Several toxicities studied. RESULTS final median PEGasparaginase dose lowered 450 . Overall, 97% all nonallergic > 100 IU/L. Asparagine < 0.5 μM in 96% 67% respectively. Ten percent developed reaction which 40% silent inactivations. cumulative incidence grade 3-4 pancreatitis, central neurotoxicity, thromboses 12%, 4%, 6%, respectively, not associated activity levels. During intensification, 50% had increased ALT 3% hyperbilirubinemia (both 3/4 correlated levels), 37% hypertriglyceridemia. Hypertriglyceridemia occurred less intensification compared ALL-10 (37% v 47%), is similar but higher during intensification. CONCLUSION results significant reduction adequate sufficient asparagine depletion. addition, TDM, inactivation allergic-like reactions identified. However, reduced limited.