1 INTRODUCTION
Acute Lymphoblastic Leukemia (ALL) is the most common cancer in children
as it represents approximately 25% of cancer diagnoses among children
below 15 years. Management of ALL has evolved over many decades; with a
risk-based approach, treatment intensification, and better supportive
care, survival rates in children have progressively risen to nearly
90%.1 L‑Asparaginase is an integral component of
treatment for children with ALL and since its introduction by the Dana
Farber group in 1977 into pediatric treatment protocols survival has
significantly improved.2,3
There are three currently available L-Asparaginase preparations approved
for clinical applications: Escherichia coli derived native E.coli
Asparaginase, PEGylated Asparaginase (PEG Asparaginase), and Erwinia
chrysanthemi derived Erwinia Asparaginase. All presently available
Asparaginase preparations share the same mechanism of action – the
deamination and depletion of asparagine, an essential amino acid for the
lymphoblast. Yet, each displays a markedly different pharmacokinetic
profile.4,5. PEG Asparaginase has a significantly
longer half-life and is less immunogenic than the native
Asparaginase.6 When used in front-line therapy to
replace native Asparaginase as part of combination chemotherapy, PEG
Asparaginase has shown comparable efficacy.7
In clinical practice, the enzyme is currently given by the intravenous,
intramuscular or subcutaneous route, with dosages being different across
various protocols followed.8 Asparaginase activity of
100 IU/L at desired time point for the molecule is considered to be
sufficient for complete asparagine depletion.9Although this might theoretically result in different pharmacokinetic
profiles, information on the comparability of the routes of
administration is limited about the currently available preparations.
Therapeutic drug monitoring of Serum Asparaginase Activity (SAA) level
helps individualise Asparaginase dosing. The common side effects
encountered with Asparaginase are hypersensitivity reactions, silent
inactivation, cerebral sinus venous thrombosis, pancreatitis,
hyperglycemia, hypertriglyceridemia, and liver dysfunction
(hyperbilirubinemia and transaminitis). There is heterogeneity among
healthcare providers in the usage of L-Asparaginase concerning
preparations used, doses and route of administration, therapeutic drug
monitoring, and toxicity profile observed along with dilemma of choosing
a bioequivalent drug. The present survey attempts to understand the
Asparaginase usage practice among healthcare providers in India, which
will pave the way for effective designing of future clinical trials
associated with pediatric oncology.