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Asparaginase in ALL
Amplifying the Academic/Community Connection for Optimizing Asparaginase Therapy in ALL

Released: January 13, 2026

Amir T. Fathi
Amir T. Fathi, MD
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Key Takeaways
  • ASNase remains a cornerstone therapy for pediatric, AYA, and adult ALL. Erwinia-based ASNase can be used to replace E coli–derived products after hypersensitivity reaction development.
  • Preexisting fatty liver disease may increase the risk of liver injury with ASNase, but treatment with asparaginase is usually still feasible; however, experts recommend dose reductions, proactive planning, and close monitoring to limit hepatotoxicity and avoid therapy delays.
  • Encephalopathy can occur with asparaginase use. Experts recommend a symptom-driven approach for monitoring, particularly when encephalopathy develops or neuropsychiatric symptoms lack a clear etiology.

In this commentary, experts Amir T. Fathi, MD and Shira Dinner, MD, address key frequently asked questions about the use of asparaginase (ASNase) in the management of pediatric, adolescent and young adult (AYA), and adult patients with a diagnosis of acute lymphoblastic leukemia (ALL). This commentary also summarizes key insights and actionable takeaways for community practitioners gathered from qualitative interviews with oncology healthcare professionals (HCPs).

Do you monitor ammonia levels routinely, and if so, what thresholds prompt intervention?

Amir T. Fathi, MD:
ASNase catalyzes the hydrolysis of asparagine into aspartic acid and ammonia, and its efficacy can be determined by measuring the levels of ASNase activity. Malignant leukemia cells, like those in ALL, are uniquely sensitive to depletion of plasma asparagine. Normal cells make their own asparagine, but ALL cells cannot. Pharmacologic administration of ASNase works as an early form of targeted therapy because tumor cells essentially run out of this amino acid, leading to cell death. It is difficult to measure asparagine depletion. Although ammonia levels have been suggested to reflect ASNase activity, this is not done routinely for this purpose. I do not routinely monitor ammonia levels unless there is some degree of encephalopathy, which can occur with ASNase therapy, or unless it becomes challenging to pinpoint a root cause of the patient’s symptoms. In summary, I do not use numeric thresholds but rather a symptom-triggered approach.

What is your approach or strategies for patients with preexisting fatty liver disease?  

Amir T. Fathi, MD:
Some degree of evidence does suggest that patients with fatty liver disease, which is becoming increasingly recognized in the United States, have a higher risk of liver injury following ASNase treatment. In general, I don't think ASNase is off the table in such patients, but dose reductions and close monitoring are recommended to prevent liver injury. Further, liver injury does not frequently recur, but once it does, it can be challenging because it can delay subsequent therapies. However, HCPs need to be proactive. I recommend therapeutic dose monitoring (TDM) and ASNase dose reductions so that these patients can tolerate ASNase treatment and benefit from it. Guideline-based approaches to prevention and management of liver injury through laboratory assessments, supportive measures and medications, and close follow-up are very important.

Shira Dinner, MD:
Liver toxicity occurs most commonly after the first dose of ASNase but can occur after subsequent doses. Typically, liver damage is not permanent; it is reversible but can sometimes take weeks to resolve. It could delay or necessitate dose reduction in the next cycle of chemotherapy. To decrease the risk of hepatotoxicity, I recommend HCPs aim to synchronize the timing of ASNase with daunorubicin, a myelosuppressive drug that is often used in the induction regimen.

Ultimately, the goal is to preserve asparaginase’s therapeutic benefit while anticipating and managing toxicity early, rather than reacting after treatment delays occur. The section below distills the above discussion into actionable clinical pearls HCPs can apply across diverse  populations of patients with ALL.

Clinical Pearls and Actionable Takeaways
Key takeaways from the live program include the fact that ASNase remains a potent and vital antileukemic drug—a cornerstone for treating patients with ALL. The role of ASNase persists, even with the integration of targeted immunotherapies such as blinatumomab. Standard practice involves ASNase-containing, pediatric-inspired regimens, based on Children's Oncology Group protocols and informed by adult clinical trials (eg, CALGB 10403, ECOG-ACRIN E1910). Pediatric-inspired regimens can often be used preferentially for patients younger than 39 years of age, depending on fitness and performance status.

Therapeutic drug monitoring (TDM) is standard practice in pediatric oncology settings. In adult ALL centers, routine TDM implementation is highly variable, though there is an institutional drive toward formalizing protocols to ensure patients are receiving therapeutic benefit. TDM with serum asparaginase activity measurements is essential for early detection of “silent inactivation,” wherein antibodies are produced following ASNase therapy and prevent its function, leading to suboptimal asparagine depletion. Of importance, there is no cross-reactivity between E coli‒derived products and Erwinia ASNase–based products. Thus, Erwinia ASNase–based products can be used to replace pegaspargase or calaspargase pegol following allergy development.

Premedication (eg, steroids, diphenhydramine, acetaminophen, H2 blockers) is standard practice prior to Erwinia ASNase administration in patients with ALL but it can mask hypersensitivity symptoms, and nurses play a critical role in recognizing typical symptoms of hypersensitivity.

ASNase is associated with impactful adverse events, including organ injury (pancreas, liver), allergic reactions, and thrombosis. Liver transaminase elevations are common, are generally manageable, and usually do not require discontinuation of the drug. It is important to follow guideline-based approaches to prevent and manage these events including laboratory assessments, supportive measures and medications, close follow-up, and patient education/communication.

Your Thoughts
What challenges have you encountered in managing patients with ALL using asparaginase? Answer the polling question and browse the program page to access available slides and watch an on-demand webcast to learn more on this topic.

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How often do you switch patients from pegaspargase or calaspargase pegol to Erwinia ASNase–based products due to allergy development?

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