An observational study reported in The Lancet Oncology by -Wolthers et al in the Ponte di Legno Toxicity Working Group identified characteristics and the course of asparaginase-associated pancreatitis in childhood acute lymphoblastic leukemia. Kjeld Schmiegelow, MD, of The University Hospital Rigshospitalet, is the corresponding author of The Lancet Oncology article.
The study involved merged data from patient files from 26 trials by 18 trial groups on children aged 1.0 to 17.9 years diagnosed with t(9;22)-negative acute lymphoblastic leukemia between June 1996 and January 2016 who developed asparaginase-associated pancreatitis within 50 days of asparaginase exposure.
A total of 465 patients with asparaginase-associated pancreatitis were identified. Among those with available data, 33 of 424 (8%) required mechanical ventilation, 109 of 422 (26%) developed pseudocysts, 81 of 393 (21%) needed insulin therapy, and 7 of 458 (2%) died.
Risk of assisted mechanical ventilation, need for insulin, pseudocysts, or death was associated with older age (median ages for patients with vs without complications = 10.5 vs 6.1 years, P < .0001) and with having one or more vs no affected vital signs (fever, hypotension, tachycardia, or tachypnea; 44% vs 24%, P = .02).
At 1 year after diagnosis of pancreatitis, 31 of 275 patients (11%) still needed insulin or had recurrent abdominal pain. Both were associated with having developed pseudocysts (odds ratio [OR] = 9.48, P = .0002 for insulin; OR = 11.79, P < .0001 for abdominal pain).Within 8 years of asparaginase-associated pancreatitis, the risk of abdominal symptoms decreased from 8% to 0%, but the need for insulin was constant at 9%.
Among 96 patients re-exposed to asparaginase (including 59 after severe asparaginase-associated pancreatitis), 44 (46%) developed a second asparaginase-associated pancreatitis (severe in 52%). Risk of persisting need for insulin or abdominal pain after two vs one episode of pancreatitis did not differ (7% vs 12%, P = .51). Risk of a second episode was not associated with any baseline characteristics.
The investigators concluded: “Since the risk of a second asparaginase-associated pancreatitis was not associated with severity of the first asparaginase-associated pancreatitis and a second asparaginase-associated pancreatitis did not involve an increased risk of complications, asparaginase re-exposure should be determined mainly by the anticipated need for asparaginase for anti-leukaemic efficacy. A study of the genetic risk factors identifying patients in whom asparaginase exposure should be restricted is needed.”
The study was funded by The Danish Childhood Cancer Foundation and The Danish Cancer Society. ■