Written in Blood
Obesity Has Early and Lasting Effects on Children with ALL
determined by the absence of leukemia cells in the bone marrow
in the setting of recovered blood counts. Minimal residual disease
(MRD) takes this assessment a step further, in identifying remaining
leukemia cells using more sensitive technology, such as flow cytometry.
According to the authors, led by Etan Orgel, MD, of the Children’s
Hospital Los Angeles, MRD is among the strongest predictors of
long-term survival and disease recurrence. However, they noted,
“Whether obesity poses a uniform risk during this period or whether it
contributes greater influence during
certain phases of treatment has yet
to be investigated.”
The investigators hypothesized
that obesity during remission
induction therapy is associated with
Bone pain was the most frequent treatment-emergent adverse reaction that
persistent leukemia – as seen on endoccurred in at least 1% or greater in patients treated with GRANIX at the recommended dose and was numerically two times more frequent than in the placebo
of-induction MRD positivity– due in
group. The overall incidence of bone pain in Cycle 1 of treatment was 3.4%
part to the “active” nature of adipo(3.4% GRANIX, 1.4% placebo, 7.5% non-US-approved filgrastim product).
Leukocytosis
cytes (fat cells) in the regulation of
In clinical studies, leukocytosis (WBC counts > 100,000 x 106/L) was observed
chemotherapy response in patients
in less than 1% patients with non-myeloid malignancies receiving GRANIX.
with ALL cell lines.
No complications attributable to leukocytosis were reported in clinical studies.
6.2 Immunogenicity
To test that hypothesis, the
As with all therapeutic proteins, there is a potential for immunogenicity. The
investigators analyzed a cohort of
incidence of antibody development in patients receiving GRANIX has not
been adequately determined.
198 pediatric patients who were
7 DRUG INTERACTIONS
diagnosed with BP-ALL between the
No formal drug interaction studies between GRANIX and other drugs have
ages of 1 and 21. All patients were
been performed.
Drugs which may potentiate the release of neutrophils‚ such as lithium‚
treated with Children’s Oncology
should be used with caution.
Group induction chemotherapy
Increased hematopoietic activity of the bone marrow in response to growth
factor therapy has been associated with transient positive bone imaging
regimens for one month, either as
changes. This should be considered when interpreting bone-imaging results.
a three-drug or four-drug regimen,
8 USE IN SPECIFIC POPULATIONS
depending on the patient’s risk level.
8.1 Pregnancy
Pregnancy Category C
Investigators assessed the influence
There are no adequate and well-controlled studies of GRANIX in pregnant
of BMI on risk of MRD in the bone
women. In an embryofetal developmental study, treatment of pregnant rabbits with tbo-filgrastim resulted in adverse embryofetal findings, including
marrow; MRD was determined
increased spontaneous abortion and fetal malformations at a maternally toxic
from flow cytometry analysis of
dose. GRANIX should be used during pregnancy only if the potential benefit
bone marrow specimens collected at
justifies the potential risk to the fetus.
In the embryofetal developmental study, pregnant rabbits were administered
the end of induction therapy.
subcutaneous doses of tbo-filgrastim during the period of organogenesis
Approximately one-third of the
at 1, 10 and 100 mcg/kg/day. Increased abortions were evident in rabbits
treated with tbo-filgrastim at 100 mcg/kg/day. This dose was maternally toxic
cohort was classified as overweight
as demonstrated by reduced body weight. Other embryofetal findings at this
(n=30; 15.2%) or obese (n=41;
dose level consisted of post-implantation loss‚ decrease in mean live litter
20.7%) at the time of diagnosis. More
size a