Asparaginase-associated pancreatitis in children with acute lymphoblastic leukaemia in the NOPHO ALL2008 protocol

TY - JOUR

T1 - Asparaginase-associated pancreatitis in children with acute lymphoblastic leukaemia in the NOPHO ALL2008 protocol

AU - Raja, Raheel A

AU - Schmiegelow, Kjeld

AU - Albertsen, Birgitte K

AU - Prunsild, Kaie

AU - Zeller, Bernward

AU - Vaitkeviciene, Goda

AU - Abrahamsson, Jonas

AU - Heyman, Mats

AU - Taskinen, Mervi

AU - Harila-Saari, Arja

AU - Kanerva, Jukka

AU - Frandsen, Thomas L

AU - Nordic Society of Paediatric Haematology and Oncology (NOPHO) group

N1 - © 2014 John Wiley & Sons Ltd.

PY - 2014/4

Y1 - 2014/4

N2 - L-asparaginase is an important drug in the treatment of childhood acute lymphoblastic leukaemia (ALL). Treatment is associated with several toxicities, including acute pancreatitis. Clinical course, presentation, re-exposure to L-asparginase after pancreatitis and risk of recurrent pancreatitis within an asparaginase-intensive protocol has been poorly reported. Children (1-17 years) on the ongoing Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol with asparaginase-associated pancreatitis (AAP) diagnosed between 2008 and 2012 were identified through the online NOPHO ALL toxicity registry. NOPHO ALL2008 includes eight or 15 doses of intramuscular pegylated L-asparginase (PEG-asparaginase) 1000 iu/m(2) /dose at 2-6 weeks intervals, with a total of 30 weeks of exposure to PEG-asparaginase (clinicaltrials.gov no: NCT00819351). Of 786 children, 45 were diagnosed with AAP with a cumulative risk of AAP of 5·9%. AAP occurred after a median of five doses (range 1-13), and 11 d (median) from the latest administration of PEG-Asparaginase. Thirteen patients developed pseudocysts (30%) and 11 patients developed necrosis (25%). One patient died from pancreatitis. Twelve AAP patients were re-exposed to L-asparginase, two of whom developed mild AAP once more, after four and six doses respectively. In conclusion, re-exposure to PEG-asparaginase in ALL patients with mild AAP seems safe.

AB - L-asparaginase is an important drug in the treatment of childhood acute lymphoblastic leukaemia (ALL). Treatment is associated with several toxicities, including acute pancreatitis. Clinical course, presentation, re-exposure to L-asparginase after pancreatitis and risk of recurrent pancreatitis within an asparaginase-intensive protocol has been poorly reported. Children (1-17 years) on the ongoing Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol with asparaginase-associated pancreatitis (AAP) diagnosed between 2008 and 2012 were identified through the online NOPHO ALL toxicity registry. NOPHO ALL2008 includes eight or 15 doses of intramuscular pegylated L-asparginase (PEG-asparaginase) 1000 iu/m(2) /dose at 2-6 weeks intervals, with a total of 30 weeks of exposure to PEG-asparaginase (clinicaltrials.gov no: NCT00819351). Of 786 children, 45 were diagnosed with AAP with a cumulative risk of AAP of 5·9%. AAP occurred after a median of five doses (range 1-13), and 11 d (median) from the latest administration of PEG-Asparaginase. Thirteen patients developed pseudocysts (30%) and 11 patients developed necrosis (25%). One patient died from pancreatitis. Twelve AAP patients were re-exposed to L-asparginase, two of whom developed mild AAP once more, after four and six doses respectively. In conclusion, re-exposure to PEG-asparaginase in ALL patients with mild AAP seems safe.

KW - Adolescent

KW - Antineoplastic Agents

KW - Antineoplastic Combined Chemotherapy Protocols

KW - Asparaginase

KW - Child

KW - Child, Preschool

KW - Female

KW - Humans

KW - Infant

KW - Male

KW - Pancreatitis

KW - Polyethylene Glycols

KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma

KW - Treatment Outcome

U2 - 10.1111/bjh.12733

DO - 10.1111/bjh.12733

M3 - Journal article

C2 - 24428625

SN - 0963-1860

VL - 165

SP - 126

EP - 133

JO - British Journal of Haematology, Supplement

JF - British Journal of Haematology, Supplement

IS - 1

ER -