Expert recommendations for pancreatitis/pancreatic necrosis treatment after L-asparaginase in children with acute lymphoblastic leukemia

L-asparaginase is one of the most effective drugs in pediatric and adult acute lymphoblastic leukemia treatment. But drug side effects are an important problem. pancreatitis and pancreatic necrosis are not common (2–18 %) complication, but high chance of severe disease with fatal outcome make to bring in careful attention of pediatric oncologists-hematologists, surgeons, intensivists, radiologists. Recognizing multidisciplinary importance of this problem, at June 21^st, 2023 at Morozov Children’s Clinical hospital a Round table on pancreatitis/pancreatic necrosis after L-asparaginase use was organized. This article presents expert recommendations from federal and regional clinics in diagnosis and treatment of such severe complication.

1. Campbell M., Kiss C., Zimmermann M. et al. Childhood acute lymphoblastic leukemia: results of the randomized acute lymphoblastic leukemia Intercontinental-Berlin-Frankfurt-Münster 2009 trial. J Clin Oncol 2023;41(19):3499–511. DOI: 10.1200/JCO.22.01760

2. Valiev T.T., Shervashidze M.A., Osipova I.V. et al. ALL-IC BFM 2002 protocol: treatment results of acute lymphoblastic leukemia in children in a multicenter clinical trial. Klinicheskaya onkogematologiya. Fundamentalnye issledovaniya i klinicheskaya praktika = Clinical Oncohematology. Basic Research and Clinical Practice 2022;15(2):119–29. (In Russ.).

3. Wetzler M., Sanford B., Kurtzberg J. et al. Effective asparagine depletion with pegylated asparaginase results in improved outcomes in adult acute lymphoblastic leukemia: Cancer and Leukemia Group B Study 9511. Blood 2007;109(10):4164–7. DOI: 10.1182/blood-2006-09-045351

4. Korkina Yu.S., Valiev Т.Т. Asparaginase drugs: a new view of the mechanism of action, side effects and experience in BFM (Berlin–Frankfurt–Mȕnster) protocols. Rossiyskiy zhurnal detskoy gematologii i onkologii = Russian Journal of Pediatric Hematology and Oncology 2021;8(4):81–9. (In Russ.). DOI: 10.21682/2311-1267-2021-8-4-81-89

5. Egler R.A., Ahuja S.P., Matloub Y. et al. L-asparaginase in the treatment of patients with acute lymphoblastic leukemia. J Pharmacol Pharmacother 2016;7(2):62–71. DOI: 10.4103/0976-500X.184769

6. Pession A., Valsecchi M.G., Masera G. et al. Long-term results of a randomized trial on extended use of high dose L-asparaginase for standard risk childhood acute lymphoblastic leukemia. J Clin Oncol 2005;23(28):7161–7. DOI: 10.1200/JCO.2005.11.411

7. Keating M.J., Holmes R., Lerner S. et al. L-asparaginase and PEG asparaginase – past, present, and future. Leuk Lymphoma 1993:10(Suppl):153–7. DOI: 10.3109/10428199309149129

8. Bagnenko S.F., Tolstoy A.D., Krasnogorov V.B. et al. Acute pancreatitis (DIAgnostic protocols and treatment). Annaly khirurgicheskoy gepatologii = Annals of Surgical Hepatology 2006;11(1):60–6. (In Russ.).

9. Rasheed A., Gallagher S.F. Acute Pancreatitis Classification Working Group. Classification of acute pancreatitis 2012: revision of the Atlanta classification and definitions by international consensus. Gut 2013;62(1):102–11.

10. Tolstoy A.D. Parapancreatitis (etiology, pathogenesis, diagnosis, treatment). Saint Petersburg, 2003. 256 p. (In Russ.).

11. Kloos R.Q.H., Pieters R., Jumelet F.M.V. et al. Individualized asparaginase dosing in childhood acute lymphoblastic leukemia. J Clin Oncol 2020;38(7):715–74. DOI: 10.1200/JCO.19.02292

12. Rank C.U., Wolthers B.O., Grell K. et al. Asparaginase-associated pancreatitis in acute lymphoblastic leukemia: results from the NOPHO ALL2008 treatment of patients 1–45 years of age. J Clin Oncol 2020;38(2):145–54. DOI: 10.1200/JCO.19.02208

13. Schmiegelow K., Rank C.U., Stock W. et al. SOHO state of the art updates and next questions: management of asparaginase toxicity in adolescents and young adults with acute lymphoblastic leukemia. Clin Lymphoma Myeloma Leuk 2021;21(11):725–33. DOI: 10.1016/j.clml.2021.07.009

14. Liu C., Yang W., Devidas M. et al. Clinical and genetic risk factors for acute pancreatitis in patients with acute lymphoblastic leukemia. J Clin Oncol 2016;34(18):2133–40. DOI: 10.1200/JCO.2015.64.5812

15. Lynggaard L.S., Rank C.U., Hansen S.N. et al. Asparaginase enzyme activity levels and toxicity in childhood acute lymphoblastic leukemia: a NOPHO ALL2008 study. Blood Adv 2022;6(1):138–47. DOI: 10.1182/bloodadvances.2021005631

16. Lankisch P.G., Apte M., Banks P.A. et al. Acute pancreatitis. Lancet 2015;386(9988):85–96. DOI: 10.1016/S0140-6736(14)60649-8