A Laboratory Derived Test to Assess L-Asparaginase Levels in the Clinical Samples.

The L-asparaginase assay is a laboratory developed test (LDT) to determine the enzyme activity of L-asparaginase in patients who have been treated with Elspar®/Kidrolase®, Oncaspar®, or Erwinaze®. This assay has been validated and is performed in our CLIA certified laboratory to monitor the asparaginase activity level during a patient’s treatment.

The assay is intended to help physicians identify patients experiencing “silent inactivation” and/or rapid clearance so as to ensure that adequate asparaginase activity is present during treatment. The assay is done on a plasma or serum sample obtained from the patient after treatment. A minimal volume of sample (0.3 mL) is required and the results are usually returned by close of business on the same day that the sample is received. Hence, our assay essentially offers real-time therapeutic monitoring of the asparaginase levels in the treated patient.  An “algorithm” of when to submit samples for analysis has been developed (1) (and is posted on this site along with other relevant papers – see the “Additional References” link, below)

What is L-asparaginase?

L-asparaginase is a high molecular weight enzyme which often induces an immune response in a significant percentage of treated patients. (2)  There are two forms of hypersensitivity seen in clinical practice. Clinical hypersensitivity ranges from a mild local injection site reaction to full blown anaphylaxis.(3) Since asparaginase derived from E. coli is frequently used as first treatment, patients who develop a reaction are switched to Erwinaze (derived from Erwinia chrysanthemi) to continue their treatment because of the lack of cross-reactivity of anti-E. coli antibodies to Erwinaze.(4)

The second form of hypersensitivity is when antibodies are formed, but the patients do not experience any clinical signs of hypersensitivity. Even though there are no outward symptoms, these antibodies can either inactivate the enzyme or enhance the metabolism of asparaginase such that the patient may not have adequate serum or plasma activity levels to achieve an anti-leukemic effect (often referred to as “silent inactivation” or “silent hypersensitivity”).(5)

As a result, hypersensitivity to L-asparaginase is a clinically relevant issue regardless of the source from which the drug is prepared.(3)

NOTE: The performance characteristics of this test were validated by NEXT Molecular Analytics. The U.S. Food and Drug Administration (FDA) has not approved or cleared this test; however, FDA approval or clearance is currently not required for clinical use of this test. The results are not intended to be used as the sole means for clinical diagnosis or patient management decisions. Next Molecular Analytics is authorized under Clinical Laboratory Improvement Amendments (CLIA) to perform high-complexity testing.

1. Bleyer A, Asselin B, Koontz S, Hunger S.  Pediatr Blood Cancer . 2015;62: 1102-1105.

2. Woo MH, Hak LJ, Storm MC et al. Hypersensitivity or development of antibodies to asparaginase does not impact treatment outcome of childhood acute lymphoblastic leukemia. Journal of  Clinical Oncology, 2000;18:1525-1532.

3. Raetz EA, Salzer WL. Tolerability and efficacy of L-asparaginase therapy in pediatric patients with acute lymphoblastic leukemia. Journal of Pediatric Hematology Oncology, 2010; 32:554-563.

4. Wang, B., Relling, MV, Storm, MC et al. Evaluatoin of immunologic corss reaction of anti-asparagainase3 antibodies in acute lymphoblastic leukemia (ALL) and lympohoma patients. Leukemia 2003; 17:1583-1588.

5. Pieters R, Hunger S, Boos J, et al. L-asparaginase treatment in acute lymphoblastic leukemia: a focus on Erwinia asparaginase. Cancer,2011;117:238-249.