221
a
factor
50). ~’
revealed
as
risk
(n
recipients, although subgroup analysis suggested days
analysis
overweight
group
of TPNwas
associated
for
for adults with HLA-matched donors
significantly
only
autologous
only
of whom95%
the OralMucositisAssessment
a
a
cohort
of 2238
In
Scale,
Using
patients.
study
hematologic malignancies, Deeg
large
subjects,
et alls
at
with
demon- new
to assist
data
had
grading system
comparative
Horowitz
et
a123
150
between
strated
centers,
mortality
day
post-
ideal
com-
transplant
similar
association between mucositis
recently
significantly higher
a
adults
to 95% ideal
described
(<95%
transplant among underweight
of
A
and children
and the risk
infection.
few small studies
withnon-metab-
(85%
severity
weight)
weight)
with all
>95%
was noted
but this association was not
Dickson et a119
ideal weight. Atrend for
have assessed intestinal
subjects
permeability
pared
in
children
ideal
olized
an association of
infection
no association with mucositis
<85%
altered
perme-
higher mortality
probes, finding
with
a
unfortu-
rate,24 but,
statistically sig-
ability
higher
weight,
described
a
In
nificant.
Likewise,
recently
in
nately,
severity. 25
increase in
a
other
disassociation has been noted between
oral mucositis and fatal veno-occlusive disease
(VOD)
studies,
early mortality
significant
underweight
mass
but not over-
index)
(<80%
age-adjusted body
in
a
multivariate
of
of the
that
evaluations
oral
may
weightpatients
regression analysis
liver, suggesting
473adults
HCTfor
not mirror the
of visceral
autologous
severity
undergoing
hematologic
regimen-related
associatedwiththe
Long-term
malignancies.
mortality
toXiCity.26
was
for both
the Dickson tested
estimate of tious
Over the
a
of
have been
treatment, however,
significantly higher
years,
variety
strategies
in
to
oral
reduce and
and
and their infec-
involved bowel
non-
underweight
overweight patients
gut toxicity
as measured
a
The earliest
study,
by
Kaplan-Meier
sequelae.
attempts
Therewereno
but
tolerated
sterilization,
oral,
5-yearnon-relapsemortality.
significant
rates
patients poorly
on estimates
or
absorbable antimicrobials.
and antiviral
with
effects
in either
of
survival
5-year
or
relapse
Prophylaxis
has aided
systemic
which
dose
antifungal
in
agents
immensely
underweight
overweight patients,
reassured these researchers that
in
oral and
which otherwise
under examina-
infections,
currently
chemotherapy
gut
Measures
preventing
was not
delayed
tion to
adjustments
overweight patients
resulting
healing.
in
mucositis include both
underdosing.
protect against
topical
It is
to
studies in
these
a
mean-
factor
the hemato-
difficult
beta,
agents (transforming growth
synthesize
ingfulwayfor clinical practice.
poietic growth
do
factors G-CSF and
and
GM-CSF)
sys-
However,
they
signal
as
interleukin-
the needto consider extremes of
status
temic
(keratinocyte
factor,
bodyweight
agents
growth
and
Glutamine also has
variables in research
Researchers must
11, amifostine,
study design.
lisofylline).27
the
of altered
as both
a
and
also continue to
relevance
been
body
investigated
topical
systemic agent.
pursue
habitus to outcome in HCT and the
if
for
role,
any,
of
and
intervention,
underweight patients
pretransplant
especially repletion
Glutamine and mucosal
Nutrient
toxicity
or better
recognition
to nutritionalriskfactors atthetimeofinitial
with
doses of
response
diagnosis
manipulation
pharmacologic
and treatment.
the
that obese
has
to nutritionists because ofits
Unfortunately,
reported
glutamine
the
despite
appealed
of
it has been
fuel for
oxidative
and
role as
paucity
research,
primary
enterocytes
are denied
because ofthe concern
dose
HCToccurs in an
patients
transplants
lymphocytes.
essentially glutamine-
of
for the
and
of
environment
owingto
by
chemoradiotherapy
depletion
free
the
safety
efficacy
chemotherapy
regi-
glutathione
mens based on
stores
and the
on
weight.2o
dependence
glutamine-free TPNfor anextended time. The earliest
trial conducted
et a128 in 45
by
Zeigler
widely
allogeneic
the
TPNon
REDUCE
STRATEGIES TO
CONDITIONING-RELATED
has been
influence of
infection outcome and
referenced to
patients
positive
support
TOXICITIES AND RELIANCE ON TPN
glutamine-supplemented
Conventional
are
of
IV
This
transplant preparative regimens
the most intensive used in
hospital length
stay.
The
is
double-blind trial
dose
randomized,
therapies
oncology.
provided
glutamine
metaboli-
a
as
of marrow ablative
associated
0.57
determined
toxicity
dose-limiting
regimens
g/kg,
previously
with the
and
from
one
almost
tract or
safe,29
always
gastrointestinal
cally
neurologically
day
post-HCT
those
total
until oral intake reached 50% of estimated
liver,
especially
alkylating
containing
body
energy
study
this
Statistical flaws of
needs for three
were lack ofan
irradiation,
agents (cyclophosphamide,
days.
a
and failure to ana-
and
and
busulfan,
melphalan,
priori hypothesis
thiotepa),
etoposide.21
as intent to treat.
determined to be
which
was
The
of the mucosal barrier and bacterial
balance,
glutamine
Nitrogen
disruption
lyze
in
the
control
-~-
to the
of infec-
translocation contribute
tion and fevers of unknown
( -1.4
pathogenesis
in the
superior
the
of
0.5
with
(-4.2 ~-- 1.2
origin
period
g) compared
was calculated on
group
the
g),
after
the
It is dif-
one-halfof
a
sam-
only
patients;
entire
neutropenia immediately
cytoreduction.
ficult to assess
ofthe
size calculation
of oral mucositis or diarrheal have been accruedfor
the
should
the
directly
grading
integrity
gastrointes-
ple
suggests
sample
tinal
so
a
difference of3
tract,
g/d. Finally,
stool volumes have often served as
a
for
did not use an
surrogate
the
investigators
objective, reproducible
a
overall
et a122
for
that
blood
or
definition
is,
infections,
toxicity.
positive
that
Rappaport
proposed
peak
mucositis score and
ofTPN
as
in
occurred the
relevant
as
tissue culture. Ofthe 10 infections
days
required
in trials
to evaluate
control
four had
three had celluli-
bacteremias,
designed
end-points
agents
gut
group,
Both these indices were associated with
or
tis
catheter exit sites that
in cul-
protectants.
grew organisms
in
and
a
increased blood infections
evaluation
and three
non-culture
had
proven
ture,
The
prospective
pneumonias.
not be main-
of
would
.047)
126)
(n
(n
76)
allogeneic
autologous
graft
significance (p
likely
Theus et al.
