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Relapse Following Truncation of Asparaginase in NOPHO ALL2008

Konferensbidrag (offentliggjort, men ej förlagsutgivet)
Författare S Gottschalk Højfeldt
K Grell
Jonas Abrahamsson
Bendik Lund
K Vettenranta
OG Jonsson
TL Frandsen
BO Wolthers
Mats Heyman
K Schmiegelow
BK Albertsen
Publicerad i 38th NOPHO Annual meeting. Aalborg, Denmark 3-7 May
Publiceringsår 2019
Publicerad vid Institutionen för kliniska vetenskaper, Avdelningen för pediatrik
Språk en
Ämneskategorier Cancer och onkologi, Pediatrik

Sammanfattning

Asparaginase related toxicities constitute a significant problem in the treatment of acute lymphoblastic leukemia (ALL); besides acute morbidity and mortality the toxicities can also cause truncation of treatment. Few studies have investigated relapse rates following asparaginase truncation, while taking asparaginase enzyme activity into account. The primary aim was to investigate if patients with truncation of asparaginase treatment or no enzyme activity (truncated) had a different risk of relapse compared to patients who had not been truncated and who had measurable enzyme activity (non-truncated). Children aged 1–17 years, diagnosed with non-high risk ALL July 2008 – March 2016 and treated according to the NOPHO ALL2008 protocol were eligible for inclusion. Excluding 140 patients with missing data, 1108 patients were included and followed from diagnosis with delayed entry at end of asparaginase treatment until relapse, competing events (death and secondary tumor), or end of follow-up. Median follow-up time was 5.54 years (interquartile range: 4.02–7.53). The 7-year cumulative incidence of relapse for the non-truncated was 6.68% (95% confidence interval [CI]: 4.72–8.63) and for the truncated 11.3% (95%CI: 7.01–15.7). The relapse-specific hazard ratio (HR) from a simple Cox regression comparing truncated vs. non-truncated was 1.76 (95%CI: 1.09–2.84, p=0.02). In a multiple analysis including MRD day 29, age group =/< 10 years, white blood cell count, and CNS status at diagnosis, the adjusted HR was 1.70 (95%CI: 1.05–2.74, p=0.03). Comparing patients who received <50% of their asparaginase doses with those who received =50% showed similar results (adjusted HR=1.84 (95%CI: 1.11–3.07, p=0.02)). No specific relapse type was found to be associated with asparaginase truncation. The relapse-specific hazard rate is significantly higher for children who had their asparaginase treatment truncated or had no enzyme activity. Our results confirm the importance of asparaginase in ALL treatment and emphasize the importance of therapeutic drug monitoring.

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