"Rapid Asparagine Depletion as a Possible Risk Marker for Pancreatitis in Children with Acute Lymphoblastic Leukemia Under Treatment with L-Asparaginase: Case Report from Five Patients"

Abstract

We will be describing our experience with five patients diagnosed with acute lymphoblastic leukemia (ALL), who developed L-Asparaginase (L-Asp)-induced pancreatitis during their remission induction stage. The patients were treated, at the State Cancer Center of Durango, Mexico (CECAN-Durango) since December 2021, along with a group of 30 pediatric patients (in the remission induction phase of their treatment) who did not develop pancreatitis. All patients were diagnosed with (ALL) according to criteria from the French American-British Hematology Association (FAB). Once diagnosed, patients were treated according to the St. Jude Total XV protocol. In the protocol group, L-Asp enzyme activity and asparagine (Asp) concentrations were measured on 3 occasions. Population pharmacokinetic/pharmacodynamic (PK/PD) modeling using the previously assembled and validated monolix suite software was used to determine PK/PD parameters. Four of the patients after the ninth administration and one after the sixth administration of L-Asp revealed an increase in amylase and lipase enzymes even though the patients were asymptomatic. Three of the patients had abdominal distension and diffused pain. A computed axial tomography (CAT) scan confirmed the diagnosis of pancreatitis due to the use of L-Asp, which was immediately discontinued. Regarding Asp levels, it was observed that the five patients who developed pancreatitis reached complete depletion earlier than the 30 patients without pancreatitis. By analyzing the decay slope of Asp, we found that this could be a risk. marker for the development of pancreatitis as an adverse effect of the administration of L-Asp in patients with ALL.

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“…Un estudio reciente realizado en nuestro grupo de trabajo demostró que la rápida depleción completa de Asp (< 0.1 µM) antes de las primeras 24 horas posinfusión de L-Asp puede ser un marcador de riesgo de pancreatitis en pacientes con leucemia linfoblástica aguda en tratamiento. 94…”