ASPARAGINASE ACTIVITY AND ANTI- E. COLI ASPARAGINASE ANTIBODY LEVEL MONITORING FOR DIFFERENT ASPARAGINASE PREPARATIONS IN HONG KONG CHILDHOOD ALL PATIENTS
Author(s): ,
Paroni Fan
Affiliations:
Department of Paediatrics,The Chinese University of Hong Kong,Hong Kong,Hong Kong
,
Kathy Chan
Affiliations:
Department of Paediatrics,The Chinese University of Hong Kong,Hong Kong,Hong Kong
,
Terry Chow
Affiliations:
Department of Paediatrics,The Chinese University of Hong Kong,Hong Kong,Hong Kong
,
Grace Lam
Affiliations:
Department of Paediatrics,The Chinese University of Hong Kong,Hong Kong,Hong Kong
,
Frankie Cheng
Affiliations:
Department of Paediatrics,The Chinese University of Hong Kong,Hong Kong,Hong Kong
Chi-kong Li
Affiliations:
Department of Paediatrics,The Chinese University of Hong Kong,Hong Kong,Hong Kong
EHA Library. Fan O. 05/16/19; 267687; PB1664
Oi Lam Fan
Oi Lam Fan
Contributions
Abstract

Abstract: PB1664

Type: Publication Only

Background
Asparaginase is effective for treating paediatric ALL, nonetheless, hypersensitivity reaction is the most prevalent form of adverse events in patients. Silent inactivation has been reported that some patients develop anti-asparaginase antibodies against the preparations without showing any allergic symptoms.

Currently, native E.Coli asparaginase (Leuanse) is the only licensed preparation in Hong Kong whereas pegylated E.Coli asparaginase (Oncaspar) and Erwinia asparaginase are the second-line and third-line treatment on name-patient basis respectively. In Hong Kong, the switch of preparation is guided by the presence of clinical reaction, the efficacy of the Oncaspar and difference of effectiveness between the two available brands of Erwinia asparaginase are not known. Monitoring of asparaginase activity and anti-asparaginase antibody for guiding the switch of asparaginase preparation was shown to improve patients’ outcome but have not been exercised in Hong Kong.

Aims
We aim to evaluate the implementation of asparaginase activity measurement for monitoring the efficacy of different asparaginase preparations in clinical settings.

Methods
28 patients who were undergoing asparaginase treatment were recruited including 19 newly diagnosed patients who were followed up from the start of chemotherapy. Serum was collected during induction, continuation and re-induction phase with time points corresponding to the half-life of different preparations and after allergic reaction. Serum asparaginase activity and anti-E.Coli asparaginase antibody were measured, evaluated and analysed with the grading of severity of hypersensitivity reaction.

Results
Among the 28 patients, 53.5% (N=15) of them experienced allergic reaction to Leunase; 9 of them were checked for asparaginase activity and all displayed low enzyme activity (<100U/L); anti-E.Coli asparaginase antibody level was measured for 13 of them, 75.0%  (N=10) were antibody positive (>0.625ng/mL). Among the 12 patients without reaction,61.5%(N=8) of them were positive for the antibody while all of them could maintain good activity. Most of the patients had reaction at post-induction phase, they tolerated an average of 11.4 doses of Leunase.  15 patients allergic to Leunase were switched to Oncaspar but 73.3% (N=11) were hypersensitive to the preparation at a mean dose of 1.67. Enzyme activity was quantified for 6 of them, all of them failed to maintain normal activity while 3 patients without clinical reaction and 2 of them showed suboptimal asparagianse activity.  11 patients after hypersensitivity reaction to Oncaspar were treated with two brands of Erwinia asparaginase from UK or China, namely Erwinase and Baiyun Erwinase, depending on their availability. Among them, 3 patients (27.3%) were clinically hypersensitive but all samples collected before reaction were with normal activity. Both preparation of Erwinia asparaginase achieved good anti-asparaginase activities.

Conclusion
Our results high incidence of allergy to Leunase in Chinese children. Patients allergic to Leunase were either clinically hypersensitive or silently inactivated to Oncaspar, suggesting that Oncaspar may not be a suitable alternative after Leunase allergy while the two brands of Erwinia asparaginase displayed satisfactory efficacy without triggering much hypersensitive response. Given the specificity and sensitivity, measurement of asparaginase activity should be part of the clinical monitoring to ensure adequate efficacy of different preparations.

Session topic: 2. Acute lymphoblastic leukemia - Clinical

Keyword(s): Acute lymphoblastic leukemia, Asparaginase

Abstract: PB1664

Type: Publication Only

Background
Asparaginase is effective for treating paediatric ALL, nonetheless, hypersensitivity reaction is the most prevalent form of adverse events in patients. Silent inactivation has been reported that some patients develop anti-asparaginase antibodies against the preparations without showing any allergic symptoms.

Currently, native E.Coli asparaginase (Leuanse) is the only licensed preparation in Hong Kong whereas pegylated E.Coli asparaginase (Oncaspar) and Erwinia asparaginase are the second-line and third-line treatment on name-patient basis respectively. In Hong Kong, the switch of preparation is guided by the presence of clinical reaction, the efficacy of the Oncaspar and difference of effectiveness between the two available brands of Erwinia asparaginase are not known. Monitoring of asparaginase activity and anti-asparaginase antibody for guiding the switch of asparaginase preparation was shown to improve patients’ outcome but have not been exercised in Hong Kong.

Aims
We aim to evaluate the implementation of asparaginase activity measurement for monitoring the efficacy of different asparaginase preparations in clinical settings.

Methods
28 patients who were undergoing asparaginase treatment were recruited including 19 newly diagnosed patients who were followed up from the start of chemotherapy. Serum was collected during induction, continuation and re-induction phase with time points corresponding to the half-life of different preparations and after allergic reaction. Serum asparaginase activity and anti-E.Coli asparaginase antibody were measured, evaluated and analysed with the grading of severity of hypersensitivity reaction.

Results
Among the 28 patients, 53.5% (N=15) of them experienced allergic reaction to Leunase; 9 of them were checked for asparaginase activity and all displayed low enzyme activity (<100U/L); anti-E.Coli asparaginase antibody level was measured for 13 of them, 75.0%  (N=10) were antibody positive (>0.625ng/mL). Among the 12 patients without reaction,61.5%(N=8) of them were positive for the antibody while all of them could maintain good activity. Most of the patients had reaction at post-induction phase, they tolerated an average of 11.4 doses of Leunase.  15 patients allergic to Leunase were switched to Oncaspar but 73.3% (N=11) were hypersensitive to the preparation at a mean dose of 1.67. Enzyme activity was quantified for 6 of them, all of them failed to maintain normal activity while 3 patients without clinical reaction and 2 of them showed suboptimal asparagianse activity.  11 patients after hypersensitivity reaction to Oncaspar were treated with two brands of Erwinia asparaginase from UK or China, namely Erwinase and Baiyun Erwinase, depending on their availability. Among them, 3 patients (27.3%) were clinically hypersensitive but all samples collected before reaction were with normal activity. Both preparation of Erwinia asparaginase achieved good anti-asparaginase activities.

Conclusion
Our results high incidence of allergy to Leunase in Chinese children. Patients allergic to Leunase were either clinically hypersensitive or silently inactivated to Oncaspar, suggesting that Oncaspar may not be a suitable alternative after Leunase allergy while the two brands of Erwinia asparaginase displayed satisfactory efficacy without triggering much hypersensitive response. Given the specificity and sensitivity, measurement of asparaginase activity should be part of the clinical monitoring to ensure adequate efficacy of different preparations.

Session topic: 2. Acute lymphoblastic leukemia - Clinical

Keyword(s): Acute lymphoblastic leukemia, Asparaginase

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