Risk factors of asparaginase-associated pancreatitis in children with acute lymphoblastic leukaemia
DOI:
https://doi.org/10.18203/2349-3291.ijcp20243464Keywords:
Asparaginase, Associated pancreatitis, Acute lymphoblastic leukemiaAbstract
Background: Acute lymphoblastic leukaemia (ALL) is the top childhood cancer, with survival rates of 80–85%. Attention now focuses on treatment complications. Pancreatitis, linked to Asparaginase in ALL therapy, remains poorly understood despite its recognition. The main objective of the study was to identify the risk factors of pancreatitis in children with acute lymphoblastic leukemia receiving L-Asparaginase during induction chemotherapy.
Methods: A prospective observational study was conducted at BSMMU's Paediatric Haematology and Oncology Department from March 2018 to February 2019. Newly diagnosed ALL cases in children aged 1 to 17.9 years were included, excluding those <1 or >18 years, with prior pancreatitis, or relapsed cases. Informed consent was obtained from parents/legal guardians. Diagnosis relied on clinical, CBC, bone marrow and immunophenotyping. Induction chemotherapy followed the UK ALL 2003 protocol for 35 days, with regular follow-ups monitoring abdominal symptoms and laboratory markers. USG of the abdomen was performed if pancreatitis symptoms or elevated serum amylase/lipase occurred post-L-asparaginase administration.
Results: Among 80 patients, pancreatitis affected 3 (3.8%) after the 2nd, 3rd and 7th doses of L-asparaginase, independent of individual or cumulative dosing, induction phase or concomitant medications. Age, sex, initial WBC count, ALL lineage, treatment regimen and CNS status were not statistically linked to pancreatitis incidence. Clinical manifestations included abdominal pain, tenderness, nausea, vomiting and fever, alongside elevated serum amylase and lipase levels, supported by consistent ultrasonographic findings. Despite these symptoms, no pancreatitis-related mortalities were observed, however, overall mortality during induction therapy reached 20%, unrelated to pancreatic complications.
Conclusions: In this study no significant risk factor could be identified for developing pancreatitis in ALL patients treated with asparaginase. Further studies with large sample size are required to predict who will develop pancreatic toxicity from asparaginase.
References
Sonabend RY, McKay SV, Okcu MF. ‘Hyperglycemia during induction therapy is associated with increased infectious complications in childhood acute lymphocytic leukemia’, Pediatric Blood & Cancer. 2008;51(3):387-92.
Islam A, Eden T.‘Brief report on pediatric oncology in Bangladesh’. South Asian J Cancer. 2023;2(2):105.
Lund B, Asberg A, Heyman, M. ‘Risk factors for treatment related mortality in childhood acute lymphoblastic leukaemia’, Pediatric blood and cancer. 2011;56:551–9.
Tallal L, Tan C, Oettgen H. ‘E. coli L-asparaginase in the treatment of leukemia and solid tumors in 131 children’, Cancer. 2011;25(2):306-20.
Jaffe N, Traggis D, Das L. 1971, ‘L-Asparaginase in the treatment of neoplastic diseases in children’, Cancer Research. 1971;31:942–9.
Silverman, L.B., Gelber, R.D., Dalton, V.K., et al. 2001, ‘Improved outcome for children with acute lymphoblastic leukemia: results of Dana- Farber Consortium Protocol 91-01’. Blood. 2001;97:1211-8.
Muller HJ, Boos J. ‘Use of L-asparaginase in childhood ALL’, Critical Reviews in Oncology Hematol. 1998;28:97–113.
Cohen H, Bielorai B, Harats D. ‘Conservative treatment of L-asparaginase-associated lipid abnormalities in children with acute lymphoblastic leukemia’, Pediatric Blood and Cancer. 2008;54:703–6.
Raetz EA, Salzer WL. ‘Tolerability and efficacy of L-asparaginase therapy in pediatric patients with acute lymphoblastic leukemia’. J Pediat Hematol Oncol. 2017;32:554–63.
Knoderer HM, Robarge J, Flockhart DA. Predicting asparaginase-associated pancreatitis’, Pediatric Blood and Cancer. 2011;49:634–9.
Flores-Calderon J, Exiga-Gonzalez E, Moran- Villota S. ‘Acute pancreatitis in children with acute lymphoblastic leukemia treated with L-asparaginase’. J Pediat Hematol Oncol. 2009;31:90–793.
Kearney SL, Dahlberg SE, Levy DE. ‘Clinical course and outcome in children with acute lymphoblastic leukemia and asparaginase-associated pancreatitis’. Pediatric Blood and Cancer. 2009;53:162-7.
Treepongkaruna S, Thongpak N, Pakakasama S. ‘Acute pancreatitis in children with acute lymphoblastic leukemia after chemotherapy’, Journal of Pediatric Hematology-Oncol. 2005;31:812–5.
Alvarez OA, Zimmerman G. ‘Pegaspargase- induced pancreatitis’, Medical and Pediatric Oncol. 2000;34:200–5.
Sahu S, Saika S, Pai S. ‘L-asparaginase (Leunase) induced pancreatitis in childhood acute lymphoblastic leukemia’, Pediatric Hematology Oncol. 1998;15:533–8.
Hunault-Berger M, Chevallier P, Delain M. ‘Changes in antithrombin and fibrinogen levels during induction chemotherapy with L-asparaginase in adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma. Use of supportive coagulation therapy and clinical outcome: the CAPELAL study’, Haematologica. 2008;93(10):1488-94.
Sehgal, S., Sharma, S., Chandra, J., et al. 2016, ‘Coagulation Profile at Diagnosis in Patients with Acute Lymphoblastic Leukemia’. Indian J Ped. 2016;83(10):1082-6.
Trivedi, C.D., Pitchumoni, C.S. 2005, ‘Drug-Induced Pancreatitis An Update’. J Clin Gastroenterol. 2005;39:709–16.
Weetman RM, Baehner RL. ‘Latent onset of clinical pancreatitis in children receiving L asparaginase therapy’. Cancer. 1974;34:780-5.
Weaver G. ‘Steroid-induced pancreatitis’, Gastroenterol. 1982;2:601-3.
