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Posted by on Jun 14, 2020 in Leukemia | 0 comments

In a nutshell

The study evaluated outcomes after stopping PEGasparaginase (PEG-ANAse; Oncaspar) and substituting with Erwinia ASNase (Elspar) in children with B-cell acute lymphoblastic leukemia (B-ALL). The main finding was that completely stopping ASNase was associated with poorer outcomes in such patients.

Some background

PEG-ASNase kills ALL cells by preventing them from making proteins. It is traditionally manufactured from E. coli bacteria. However, PEG-ASNase is often stopped due to toxic allergic reactions. It can be substituted with ASNase from another bacteria, Erwinia. Currently, ErwiniaASNase is unavailable due to a global shortage. The impacts of completely stopping ASNase and Erwinia substitution are unclear in children with ALL.

Methods & findings

This study included patients with newly diagnosed B-ALL from 2 clinical trials. 5,305 standard-risk (SR) patients from trial-1 and 3,081 high-risk (HR) patients from trial-2. Their induction or initial therapy included a single-dose of PEG-ASNase. This was followed by further doses based on patients’ risks and early response to therapy.

Chances of stopping PEG-ASNase over time were around 12.2% in trial-1 and 25.4% in trial-2. Chances of stopping this treatment were higher in older patients with a higher number of prescribed doses. Stopping PEG-ASNase did not impact disease-free survival (DFS; survival without signs of ALL) among SR patients from trial-1.

Among trial-2’s HR patients, 260 patients had Erwinia substitution. This was further stopped in 20% of patients. DFS was similar among patients who stopped PEG-ASNase but received all further Erwinia doses, compared to those who did not stop PEG-ANAse treatment. However, patients who did not receive all prescribed ASNase had 50% higher risks of developing cancer-related events.

The bottom line

The authors concluded that stopping ASNase in any form caused poor DFS in HR patients with B-ALL. Erwinia ASNase maintained outcomes as long as all the following doses were received.

The fine print

The study could not determine the exact number of ASNase missed doses. This might affect the results.

Published By :

Journal of clinical oncology

Date :

Apr 10, 2020

Original Title :

Impact of Asparaginase Discontinuation on Outcome in Childhood Acute Lymphoblastic Leukemia: A Report From the Children’s Oncology Group.

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