Correspondence
Monitoring
asparaginase activity
I believe the findings of
Daiane Cecconello and colleagues 1
do not provide sufficient evidence
for decision making, given the space
constraints of a Comment. Several
methodological characteristics were
not reported, and this could influence
interpretation of the findings.
The authors report that there were
fewer patients treated with leuginase
who reached an asparaginase activity
level of 0·1 UI/mL or more, than
those treated with aginasa (χ² test
p<0·001). Therefore, the authors
stated that these findings could
help decision makers to develop
adequate strategies to provide
effective treatment for patients
with acute lymphoblastic leukaemia.
Given that the above-mentioned
Comment is not based on any
previous publication, it is important
to critically review these findings
to assess its validity and relevance.
Without either the full study or
its protocol being available, it is
important to interpret these findings
with caution.
For example, the eligibility criteria
and definition of exposed and non-
exposed groups are not described.
Moreover, it is not known whether
possible confounding factors were
considered, such as nutritional
status, age, comorbidities, and
previous treatment, given that these
variables can affect asparaginase
efficacy, which is measured by serum
activity level. The study design is
not clear, and this information is
fundamentally related to the level of
evidence. Regardless of whether it
is an experimental or observational
study, methodological characteristics
must be reported to understand risk
of bias and validity of the results.
The level of evidence and strength
of recommendation are important
topics to be regarded in the decision-
making process, when risk of bias,
inconsistency, evidence indirectness,
www.thelancet.com/oncology Vol 19 November 2018 e575
imprecision, and publi­cation bias are 2 van der Sluis IM, Vrooman LM, Pieters R, et al.
Consensus expert recommendations for
all considered.
It was reported that to measure
identification and management of
asparaginase hypersensitivity and silent
asparaginase, blood samples were inactivation. Haematologica 2016;
101: 279–85.
collected before drug infusion and
24 h and 48 h after infusion. It is
noteworthy that half-life times
are different according to the type
of asparaginase, and it is not clear
whether Cecconello and colleagues
considered these differences in their
analysis. Asparaginase activity was
measured at a cutoff of concentrations
greater than 0·1 IU/mL; however, the
activity level necessary to complete
asparagine depletion remains unclear.2
Moreover, the authors emphasise the
number of deaths in the leuginase
group, although the χ² test does not
have the statistical power to support
this statement.
Biological drugs such as asparaginase
have intrinsic characteristics that can
affect clinical assessment, regulation
processes, incorporation in a health
system, and pharmacovigilance.
The Brazilian national policy on
Biological Drugs in the Unified Health
System (SUS) is being generated
with these factors in mind, with
an intensive contribution from the
Working Group, which is composed of
different stakeholders.
The level of evidence from these
findings is affected by several metho­
dological limitations. Therefore,
I recommend doing prospective
studies (experimental and obser­
vational) to adequately monitor
asparaginase activity during acute
lymphoblastic leukaemia treatment,
to support decision making in a public
health system, such as the SUS.
I declare no competing interests.
*Maria Inez Pordeus Gadelha
maria.gadelha@saude.gov.br
Chief of Staff of the Secretary of Health Care,
Ministry of Health, Brasilia, Brazil
1 Cecconello DK, Werlang ICR, Alegretti AP, et al.
Monitoring asparaginase activity in
middle-income countries. Lancet Oncol 2018;
19: 1149–50.