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

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Højfeldt , S G , Grell , K , Abrahamsson , J , Lund , B , Vettenranta , K , Jonsson , O , Frandsen , T , Wolthers , B O , Marquart , H V , Vaitkeviciene , G , Lepik , K , Heyman , M , Schmiegelow , K & Albertsen , B K 2021 , ' Relapse risk following truncation of pegylated asparaginase in childhood acute lymphoblastic leukemia ' , Blood , vol. 137 , no. 17 , pp. 2373-2382 . https://doi.org/10.1182/blood.2020006583

Title: Relapse risk following truncation of pegylated asparaginase in childhood acute lymphoblastic leukemia
Author: Højfeldt, Sofie Gottschalk; Grell, Kathrine; Abrahamsson, Jonas; Lund, Bendik; Vettenranta, Kim; Jonsson, Olafur; Frandsen, Thomas; Wolthers, Benjamin Ole; Marquart, Hanne Vibeke; Vaitkeviciene, Goda; Lepik, Kristi; Heyman, Mats; Schmiegelow, Kjeld; Albertsen, Birgitte K.
Contributor organization: HUS Children and Adolescents
Lastentautien yksikkö
Children's Hospital
Date: 2021-04-29
Language: eng
Number of pages: 10
Belongs to series: Blood
ISSN: 0006-4971
DOI: https://doi.org/10.1182/blood.2020006583
URI: http://hdl.handle.net/10138/336002
Abstract: 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/m(2) 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 enzymeactivity (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.
Subject: 3121 General medicine, internal medicine and other clinical medicine
Leukemia
CHILDREN
PANCREATITIS
INDUCTION
Peer reviewed: Yes
Usage restriction: openAccess
Self-archived version: acceptedVersion


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