In a patient with HR B ALL and severe pancreatitis due to peg-asparaginase, how do you assess the impact of peg discontinuation on risk of relapse?

We know from Gupta et al., PMID 32275469 that omission of asparaginase courses from a mBFM chemotherapy backbone has an adverse prognostic impact among NCI HR patients. In fact, complete discontinuation of asparaginase was associated with a 50% increased risk of an event among HR patients. Thus, when feasible and safe, it is in the patient's best interest to complete all asparaginase courses.

However, certain asparaginase-associated toxicities can be dose limiting, including pancreatitis. Pancreatitis is a toxicity we often grapple with given the potentially life-threatening severity that can occur. There are helpful data on the incidence and severity of pancreatitis by age group, perhaps the largest from the Ponte di Legno working group (W...

Grade 3-4 pancreatitis is considered an indication to withhold future doses of asparaginase of any form. Discontinuation of asparaginase doses is associated with inferior disease free survival in higher-risk pediatric patients with B lymphoblastic leukemia. These results seem less applicable to standard and low-risk pediatric patients with acute preB lymphoblastic leukemia.

The above results illustrate the potentially severe consequences of medication shortages (Erwinia) for pediatric oncology patients.

Gupta et al., PMID 32275469.