Relapse risk following truncation of pegylated asparaginase in childhood acute lymphoblastic leukemia.

Autor:	Gottschalk Højfeldt S; Children and Adolescent Health, Aarhus University Hospital, Aarhus, Denmark.; Institute of Clinical Medicine, Faculty of Medicine, University of Aarhus, Aarhus, Denmark., Grell K; Section of Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, Denmark.; Department of Pediatrics and Adolescent Medicine, University Hospital, Rigshospitalet, Copenhagen, Denmark., Abrahamsson J; Institution for Clinical Sciences, Sahlgrenska Academy, Department of Pediatrics, University of Gothenburg, Gothenburg, Sweden., Lund B; Department of Pediatrics, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway., Vettenranta K; Department of Pediatrics, Helsinki University Central Hospital, Helsinki, Finland., Jónsson ÓG; Department of Pediatrics, Landspitali University Hospital, Reykjavik, Iceland., Frandsen TL; Department of Pediatrics and Adolescent Medicine, University Hospital, Rigshospitalet, Copenhagen, Denmark., Wolthers BO; Department of Pediatrics and Adolescent Medicine, University Hospital, Rigshospitalet, Copenhagen, Denmark., Marquart HV; Department of Clinical Immunology, University Hospital Rigshospitalet, Copenhagen, Denmark., Vaitkeviciene G; Clinic of Children's Diseases, Faculty of Medicine, Vilnius University, Vilnius, Lithuania., Lepik K; Department of Haematology and Oncology, Tallinn Children's Hospital, Tallinn, Estonia., Heyman M; Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institut, Stockholm, Sweden.; Department of Pediatric Oncology, Karolinska University Hospital, Stockholm, Sweden; and., Schmiegelow K; Department of Pediatrics and Adolescent Medicine, University Hospital, Rigshospitalet, Copenhagen, Denmark.; Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Albertsen BK; Children and Adolescent Health, Aarhus University Hospital, Aarhus, Denmark.; Institute of Clinical Medicine, Faculty of Medicine, University of Aarhus, Aarhus, Denmark.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2021 Apr 29; Vol. 137 (17), pp. 2373-2382.
DOI:	10.1182/blood.2020006583
Abstrakt:	Truncation of asparaginase treatment due to asparaginase-related toxicities or silent inactivation (SI) is common and may increase relapse risk in acute lymphoblastic leukemia (ALL). We investigated relapse risk following suboptimal asparaginase exposure among 1401 children aged 1 to 17 years, diagnosed with ALL between July 2008 and February 2016, treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol (including extended asparaginase exposure [1000 IU/m2 intramuscularly weeks 5-33]). Patients were included with delayed entry at their last administered asparaginase treatment, or detection of SI, and followed until relapse, death, secondary malignancy, or end of follow-up (median, 5.71 years; interquartile range, 4.02-7.64). In a multiple Cox model comparing patients with (n = 358) and without (n = 1043) truncated asparaginase treatment due to clinical toxicity, the adjusted relapse-specific hazard ratio (HR; aHR) was 1.33 (95% confidence interval [CI], 0.86-2.06; P = .20). In a substudy including only patients with information on enzyme activity (n = 1115), the 7-year cumulative incidence of relapse for the 301 patients with truncation of asparaginase treatment or SI (157 hypersensitivity, 53 pancreatitis, 14 thrombosis, 31 other, 46 SI) was 11.1% (95% CI, 6.9-15.4) vs 6.7% (95% CI, 4.7-8.6) for the 814 remaining patients. The relapse-specific aHR was 1.69 (95% CI, 1.05-2.74, P=.03). The unadjusted bone marrow relapse-specific HR was 1.83 (95% CI, 1.07-3.14, P=.03) and 1.86 (95% CI, 0.90- 3.87, P=.095) for any central nervous system relapse. These results emphasize the importance of therapeutic drug monitoring and appropriate adjustment of asparaginase therapy when feasible. This trial was registered at www.clinicaltrials.gov as #NCT03987542. (© 2021 by The American Society of Hematology.)
Databáze:	MEDLINE
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