Asparaginase-associated pancreatitis in childhood acute lymphoblastic leukaemia: an observational Ponte di Legno Toxicity Working Group study

• Published in: The lancet oncology 2017-09, Vol.18 (9), p.1238-1248
• Main Authors: Wolthers, Benjamin O, Frandsen, Thomas L, Baruchel, André, Attarbaschi, Andishe, Barzilai, Shlomit, Colombini, Antonella, Escherich, Gabriele, Grell, Kathrine, Inaba, Hiroto, Kovacs, Gábor, Liang, Der-Cherng, Mateos, Marion, Mondelaers, Veerle, Möricke, Anja, Ociepa, Tomasz, Samarasinghe, Sujith, Silverman, Lewis B, van der Sluis, Inge M, Stanulla, Martin, Vrooman, Lynda M, Yano, Michihiro, Zapotocka, Ester, Schmiegelow, Kjeld
• Format: Article
• Language: English
• Subjects: Abdomen; Acute lymphoblastic leukemia; Adolescent; Age; Antineoplastic Agents - adverse effects; Asparaginase; Asparaginase - adverse effects; Cancer; Child; Child, Preschool; Childhood; Children; Cohort Studies; Cysts; E coli; Female; Health risk assessment; Humans; Infant; Leukemia; Lymphoma; Male; Pancreatitis; Pancreatitis - chemically induced; Pancreatitis - epidemiology; Pancreatitis - therapy; Patients; Pediatrics; Precursor Cell Lymphoblastic Leukemia-Lymphoma - complications; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Risk factors; Studies; Toxicity; Working groups
• ISSN: 1470-2045; 1474-5488
• DOI: 10.1016/S1470-2045(17)30424-2

Survival for childhood acute lymphoblastic leukaemia surpasses 90% with contemporary therapy; however, patients remain burdened by the severe toxic effects of treatment, including asparaginase-associated pancreatitis. To investigate the risk of complications and risk of re-exposing patients with asparaginase-associated pancreatitis to asparaginase, 18 acute lymphoblastic leukaemia trial groups merged data for this observational study. Patient files from 26 trials run by 18 trial groups were reviewed on children (aged 1·0–17·9 years) diagnosed with t(9;22)-negative acute lymphoblastic leukaemia between June 1, 1996, and Jan 1, 2016, who within 50 days of asparaginase exposure developed asparaginase-associated pancreatitis. Asparaginase-associated pancreatitis was defined by at least two criteria: abdominal pain, pancreatic enzymes at least three times the upper limit of normal (ULN), and imaging compatible with pancreatitis. Patients without sufficient data for diagnostic criteria were excluded. Primary outcomes were defined as acute and persisting complications of asparaginase-associated pancreatitis and risk of re-exposing patients who suffered an episode of asparaginase-associated pancreatitis to asparaginase. Data were collected from Feb 2, 2015, to June 30, 2016, and analysed and stored in a common database at Rigshospitalet, Copenhagen, Denmark. Of 465 patients with asparaginase-associated pancreatitis, 33 (8%) of 424 with available data needed mechanical ventilation, 109 (26%) of 422 developed pseudocysts, acute insulin therapy was needed in 81 (21%) of 393, and seven (2%) of 458 patients died. Risk of assisted mechanical ventilation, need for insulin, pseudocysts, or death was associated with older age (median age for patients with complications 10·5 years [IQR 6·4–13·8] vs without complications 6·1 years [IQR 3·6–12·2], p