Asparaginase-Associated Pancreatitis in Acute Lymphoblastic Leukemia: Results From the NOPHO ALL2008 Treatment of Patients 1-45 Years of Age.

Autor:	Rank CU; Rigshospitalet, Copenhagen, Denmark.; University of Copenhagen, Copenhagen, Denmark., Wolthers BO; Rigshospitalet, Copenhagen, Denmark., Grell K; Rigshospitalet, Copenhagen, Denmark.; University of Copenhagen, Copenhagen, Denmark., Albertsen BK; Aarhus University Hospital, Aarhus, Denmark., Frandsen TL; Rigshospitalet, Copenhagen, Denmark., Overgaard UM; Rigshospitalet, Copenhagen, Denmark., Toft N; Herlev University Hospital, Herlev, Denmark., Nielsen OJ; Rigshospitalet, Copenhagen, Denmark., Wehner PS; Odense University Hospital, Odense, Denmark., Harila-Saari A; Uppsala University Hospital, Uppsala, Sweden., Heyman MM; Karolinska University Hospital, Stockholm, Sweden., Malmros J; Karolinska University Hospital, Stockholm, Sweden., Abrahamsson J; Queen Silvia Children's Hospital, Gothenburg, Sweden., Norén-Nyström U; Umeå University, Umeå, Sweden., Tomaszewska-Toporska B; Skåne University Hospital, Lund, Sweden., Lund B; Trondheim University Hospital, Trondheim, Norway., Jarvis KB; Oslo University Hospital, Oslo, Norway.; University of Oslo, Oslo, Norway., Quist-Paulsen P; Trondheim University Hospital, Trondheim, Norway., Vaitkevičienė GE; Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania.; Vilnius University, Vilnius, Lithuania., Griškevičius L; Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania.; Vilnius University, Vilnius, Lithuania., Taskinen M; Helsinki University Hospital, Helsinki, Finland., Wartiovaara-Kautto U; Helsinki University Hospital, Helsinki, Finland., Lepik K; Tallinn Children's Hospital, Tallinn, Estonia., Punab M; Tartu University Hospital, Tartu, Estonia., Jónsson ÓG; Reykjavik University Hospital, Reykjavík, Iceland., Schmiegelow K; Rigshospitalet, Copenhagen, Denmark.; University of Copenhagen, Copenhagen, Denmark.
Jazyk:	angličtina
Zdroj:	Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2020 Jan 10; Vol. 38 (2), pp. 145-154. Date of Electronic Publication: 2019 Nov 26.
DOI:	10.1200/JCO.19.02208
Abstrakt:	Purpose: Asparaginase-associated pancreatitis (AAP) is common in patients with acute lymphoblastic leukemia (ALL), but risk differences across age groups both in relation to first-time AAP and after asparaginase re-exposure have not been explored. Patients and Methods: We prospectively registered AAP (n = 168) during treatment of 2,448 consecutive ALL patients aged 1.0-45.9 years diagnosed from July 2008 to October 2018 and treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol. Results: Compared with patients aged 1.0-9.9 years, adjusted AAP hazard ratios (HRa) were associated with higher age with almost identical HRa (1.6; 95% CI, 1.1 to 2.3; P = .02) for adolescents (10.0-17.9 years) and adults (18.0-45.9 years). The day 280 cumulative incidences of AAP were 7.0% for children (1.0-9.9 years: 95% CI, 5.4 to 8.6), 10.1% for adolescents (10.0 to 17.9 years: 95% CI, 7.0 to 13.3), and 11.0% for adults (18.0-45.9 years: 95% CI, 7.1 to 14.9; P = .03). Adolescents had increased odds of both acute (odds ratio [OR], 5.2; 95% CI, 2.1 to 13.2; P = .0005) and persisting complications (OR, 6.7; 95% CI, 2.4 to 18.4; P = .0002) compared with children (1.0-9.9 years), whereas adults had increased odds of only persisting complications (OR, 4.1; 95% CI, 1.4 to 11.8; P = .01). Fifteen of 34 asparaginase-rechallenged patients developed a second AAP. Asparaginase was truncated in 17/21 patients with AAP who subsequently developed leukemic relapse, but neither AAP nor the asparaginase truncation was associated with increased risk of relapse. Conclusion: Older children and adults had similar AAP risk, whereas morbidity was most pronounced among adolescents. Asparaginase re-exposure should be considered only for patients with an anticipated high risk of leukemic relapse, because multiple studies strongly indicate that reduction of asparaginase treatment intensity increases the risk of relapse.
Databáze:	MEDLINE
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