Successful challenges using native E. coli asparaginase after hypersensitivity reactions to PEGylated E. coli asparaginase.
OBJECTIVE
Asparaginase is an essential component of pediatric acute lymphoblastic leukemia (ALL) therapy. However, asparaginase-induced hypersensitivity reactions can compromise its efficacy either by directly influencing the pharmacokinetics of asparaginase or by leading to a discontinuation of asparaginase treatment. Here, we report successful challenges using native Escherichia coli asparaginase after previous hypersensitivity reactions to both PEGylated E. coli asparaginase and Erwinia asparaginase.


METHODS
The two patients included in this case report were diagnosed with B-precursor ALL at St. Jude Children's Research Hospital and were treated with a common regimen. Both patients developed hypersensitivity reactions to PEGylated E. coli asparaginase and Erwinia asparaginase early in treatment, and they were challenged with native E. coli asparaginase. Serum samples were collected for estimating the pharmacokinetic parameters of each patient during native E. coli asparaginase therapy.


RESULTS
Challenges with native E. coli asparaginase were successful, and asparaginase serum concentrations above therapeutic levels were attained in both patients.


CONCLUSIONS
These two cases suggest that some patients can be given native E. coli asparaginase after hypersensitivity reactions to PEGylated asparaginase and achieve therapeutic concentrations of the drug in serum.
Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105, USA.
C A
CA
Fernandez
E
E
Stewart
J C
JC
Panetta
M R
MR
Wilkinson
A R
AR
Morrison
F D
FD
Finkelman
J T
JT
Sandlund
C H
CH
Pui
S
S
Jeha
M V
MV
Relling
P K
PK
Campbell
D000293:Adolescent; D001215:Asparaginase / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D016974:Dickeya chrysanthemi / Q000201:enzymology; D004342:Drug Hypersensitivity / Q000209:etiology; D004926:Escherichia coli / Q000201:enzymology; D005260:Female; D006801:Humans; D008297:Male; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy
D011092:Polyethylene Glycols; C042705:pegaspargase; D001215:Asparaginase