Download PDF
CC BY-NC-ND 4.0 · South Asian J Cancer
DOI: 10.1055/s-0043-1767811
Original Article

Practice of L-Asparaginase Usage: A Survey among Healthcare Providers Treating Children with Cancer in India

Archana MV
1   Division of Pediatric Hematology and Oncology, Manipal Comprehensive Cancer Care Centre, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India.
,
Kalasekhar VS 
2   Department of Pediatric Oncology, Regional Cancer Centre, Trivandrum, Kerala, India
,
Vinay Munikoty
1   Division of Pediatric Hematology and Oncology, Manipal Comprehensive Cancer Care Centre, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India.
,
Ramitha R. Bhat
1   Division of Pediatric Hematology and Oncology, Manipal Comprehensive Cancer Care Centre, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India.
,
Atul Achyutrao
1   Division of Pediatric Hematology and Oncology, Manipal Comprehensive Cancer Care Centre, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India.
,
Vani Lakshmi R
3   Department of Data Science, Prasanna School of Public Health, Manipal Academy of Higher Education, Manipal, Karnataka, India
,
Vasudeva Bhat K 
1   Division of Pediatric Hematology and Oncology, Manipal Comprehensive Cancer Care Centre, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India.
› Author Affiliations
› Further Information
   Permissions and Reprints

Abstract

Zoom Image
Vasudeva Bhat K

Introduction L-asparaginase is an essential chemotherapeutic agent in the therapy of acute lymphoblastic leukemia (ALL), which has led to improvement in survival. In low- and middle-income countries like India, the outcomes in ALL are inferior compared with the published literature, one of the causes of which is believed to be due to the inferior quality of bioequivalent asparaginase.

Objective The following survey attempts to understand the practice of using this agent among oncologists treating children with cancer in our country.

Methods The researchers designed a structured online questionnaire comprising 25 aspects of L-asparaginase usage in the study. The questionnaire was directed to the healthcare providers involved in treating children with cancer in India.

Results Of the total 80 responses recorded, 51 (64%) respondents had more than 5 years of experience in pediatric oncology and were treating at least 5 to 10 newly diagnosed ALL patients per month. Forty-one (51%) respondents utilized native asparaginase, and 21 (26.3%) oncologists used PEGylated-asparaginase exclusively. The most common route of administration was the intramuscular route (66.3%). Seventy percent of respondents utilized native form at a dose of 10,000 IU/m2 and 20% at 6,000 IU/m2. The amounts used for PEGylated L-asparaginase were 1,000,IU/m2, 2,500,IU/m2, and variable doses in 48, 40, and 10% of responses, respectively. Though serum asparaginase assay (SAA) was not measured routinely in most of the centers, 39 (48.8%) healthcare providers perceived performing SAA helps to make the clinical decision.

Conclusion This survey shows a wide variation in L-asparaginase usage among healthcare providers caring for children with cancer in our country. As L-asparaginase is the pivotal component of ALL therapy, uniformity in its usage and dosing with the possibility of monitoring SAA due to the quality of bioequivalent may be one of the critical steps toward improving outcomes in ALL in our country.

Keywords

asparaginase - oncologists - pediatric ALL

Note

Presented as a poster in 53rd Congress of the International Society of Pediatric oncology (SIOP), virtual congress, October 21 to 24, 2021


Authors' Contributions

Archana MV designed the study design, collected data, and written manuscript. Vasudeva Bhat conceptualized the research, prepared the study design, and approved the final version of the manuscript. Kalashekar VS and Vinay Munikoty reviewed and approved the final version of the manuscript. Vanilakshmi analyzed the data. Ramitha and Atul helped with data collection and edited manuscript.


All authors have contributed to the manuscript in significant ways and have reviewed and agreed upon the manuscript content.


Review Board Approval

The Institutional Ethics Committee (IEC), Kasturba Hospital and Kasturba Medical College, Manipal (IEC 532/2020) approved the study protocol.




Publication History

Article published online:
10 April 2023

© 2023. MedIntel Services Pvt Ltd. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India

 

  • References

  • 1 Pui CH, Evans WE, Jacquillat C. Treatment of acute lymphoblastic leukemia. N Engl J Med 2006; 354 (02) 166-178
    CrossrefPubMedGoogle Scholar
  • 2 Sallan SE, Hitchcock-Bryan S, Gelber R, Cassady JR, Frei III E, Nathan DG. Influence of intensive asparaginase in the treatment of childhood non-T-cell acute lymphoblastic leukemia. Cancer Res 1983; 43 (11) 5601-5607
    PubMedGoogle Scholar
  • 3 Clavell LA, Gelber RD, Cohen HJ. et al. Four-agent induction and intensive asparaginase therapy for treatment of childhood acute lymphoblastic leukemia. N Engl J Med 1986; 315 (11) 657-663
    CrossrefPubMedGoogle Scholar
  • 4 Asselin BL, Whitin JC, Coppola DJ, Rupp IP, Sallan SE, Cohen HJ. Comparative pharmacokinetic studies of three asparaginase preparations. J Clin Oncol 1993; 11 (09) 1780-1786
    CrossrefPubMedGoogle Scholar
  • 5 Lanvers-Kaminsky C. Asparaginase pharmacology: challenges still to be faced. Cancer Chemother Pharmacol 2017; 79 (03) 439-450
    CrossrefPubMedGoogle Scholar
  • 6 Avramis VI, Sencer S, Periclou AP. et al. A randomized comparison of native Escherichia coli asparaginase and polyethylene glycol conjugated asparaginase for treatment of children with newly diagnosed standard-risk acute lymphoblastic leukemia: a Children's Cancer Group study. Blood 2002; 99 (06) 1986-1994
    CrossrefPubMedGoogle Scholar
  • 7 Silverman LB, Supko JG, Stevenson KE. et al. Intravenous PEG-asparaginase during remission induction in children and adolescents with newly diagnosed acute lymphoblastic leukemia. Blood 2010; 115 (07) 1351-1353
    CrossrefPubMedGoogle Scholar
  • 8 Asselin B, Rizzari C. Asparaginase pharmacokinetics and implications of therapeutic drug monitoring. Leuk Lymphoma 2015; 56 (08) 2273-2280
    CrossrefPubMedGoogle Scholar
  • 9 Brigitha LJ, Pieters R, van der Sluis IM. How much asparaginase is needed for optimal outcome in childhood acute lymphoblastic leukaemia? A systematic review. Eur J Cancer 2021; 157: 238-249
    CrossrefPubMedGoogle Scholar
  • 10 Vora A, Wade R, Mitchell C, Goulden N, Richards S. Efficacy and toxicity of pegylated asparaginase in the treatment of children and young adults with acute lymphoblastic leukaemia: results of the United Kingdom Medical Research Council (MRC) Trial UKALL 2003. Blood 2008; 112 (11) 909-909
    CrossrefGoogle Scholar
  • 11 Dinndorf PA, Gootenberg J, Cohen MH, Keegan P, Pazdur R. FDA drug approval summary: pegaspargase (oncaspar) for the first-line treatment of children with acute lymphoblastic leukemia (ALL). Oncologist 2007; 12 (08) 991-998
    CrossrefPubMedGoogle Scholar
  • 12 Place AE, Stevenson KE, Vrooman LM. et al. Intravenous pegylated asparaginase versus intramuscular native Escherichia coli L-asparaginase in newly diagnosed childhood acute lymphoblastic leukaemia (DFCI 05-001): a randomised, open-label phase 3 trial. Lancet Oncol 2015; 16 (16) 1677-1690
    CrossrefPubMedGoogle Scholar
  • 13 Cooper SL, Young DJ, Bowen CJ, Arwood NM, Poggi SG, Brown PA. Universal premedication and therapeutic drug monitoring for asparaginase-based therapy prevents infusion-associated acute adverse events and drug substitutions. Pediatr Blood Cancer 2019; 66 (08) e27797 DOI: 10.1002/PBC.27797.
    CrossrefPubMedGoogle Scholar
  • 14 Kloos RQH, Pieters R, Jumelet FMV, de Groot-Kruseman HA, van den Bos C, van der Sluis IM. Individualized asparaginase dosing in childhood acute lymphoblastic leukemia. J Clin Oncol 2020; 38 (07) 715-724
    CrossrefPubMedGoogle Scholar
  • 15 Sankaran H, Sengupta S, Purohit V. et al. A comparison of asparaginase activity in generic formulations of E. coli derived L- asparaginase: in-vitro study and retrospective analysis of asparaginase monitoring in pediatric patients with leukemia. Br J Clin Pharmacol 2020; 86 (06) 1081-1088
    CrossrefPubMedGoogle Scholar
  • 16 Sidhu J, Gogoi MP, Agarwal P. et al. Unsatisfactory quality of E. coli asparaginase biogenerics in India: implications for clinical outcomes in acute lymphoblastic leukaemia. Pediatr Blood Cancer 2021; 68 (11) e29046 DOI: 10.1002/PBC.29046.
    CrossrefPubMedGoogle Scholar
  • 17 Vyas C, Jain S, Kapoor G, Mehta A, Takkar Chugh P. Experience with generic pegylated L-asparaginase in children with acute lymphoblastic leukemia and monitoring of serum asparaginase activity. Pediatr Hematol Oncol 2018; 35 (5-6): 331-340
    CrossrefPubMedGoogle Scholar
  • 18 Hijiya N, van der Sluis IM. Asparaginase-associated toxicity in children with acute lymphoblastic leukemia. Leuk Lymphoma 2016; 57 (04) 748-757
    CrossrefPubMedGoogle Scholar
  • 19 Gupta S, Wang C, Raetz EA. et al. Impact of asparaginase discontinuation on outcome in childhood acute lymphoblastic leukemia: a report from the children's oncology group. J Clin Oncol 2020; 38 (17) 1897-1905
    CrossrefPubMedGoogle Scholar
  • 20 Gibson A, Hernandez C, Tejada FNH, Kawedia J, Rytting M, Cuglievan B. Asparaginase-associated pancreatitis in pediatric patients with acute lymphoblastic leukemia: current perspectives. Paediatr Drugs 2021; 23 (05) 457-463
    CrossrefPubMedGoogle Scholar