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Transient
Transient
By Garrett
M. Brodeur,
leukemoid
reactions
syndrome).
We
myeloblasts.
report
On
cultured
leukocyte
Leukemoid
Reaction
in a Phenotypicall.y
a
blood
and
could
be responsible
bone
disclosed
for
the
of more
leukemia
21
than
one
found
of cells
Ieukemoid
normal
have
boy
was
Robert
been
cells.
tissue,
with
perhaps
by inhibiting
may
help
and David
described
blood
for
and
K. Kalwinsky
infants
with
bone
marrow
karyotype.
These
newborns-i.e..
their
to distinguish
the
growth.
transient
trisomy
Ieukocytosis.
cells.
thus indicating
mosaicism.
diminished.
Subsequently,
a normal
in some
Mosaicism
hepatosplenomegaly,
in all
reactions
E. Tipton,
well
with
other
96% were
normal,
and the organomegaly
a predominance
the
L. Williams,
3-day-old
trisomy
transient
over
analysis
acute
normal
analysis,
advantage
chromosome
resemble
Dorothy
were
trisomic
and the
returned
to normal
marrow
a proliferative
that
phenotypically
chromosome
skin fibroblasts
count
gradually
V. DahI,
Gary
and Trisomy
21
Normal
Newborn
findings
Serial
that
may
cytogenetic
leukemoid
only
of
the
of
mosaicism
temporarily
studies,
reactions
4%
treatment,
analysis
suggest
cells
(Down
circulating
However,
Without
chromosome
trisomic
21
and
from
gain
as well
acute
as
leukemia
in infants.
A
CUTE
leukemia
occurs
with increased
in newborns
with Down
syndrome.’
to that
of
later
childhood,
the
predominant
leukemia
in infancy
is myeloblastic.2
appear
identical
to acute
myeloblastic
spontaneously
Down
tions
resolve,
syndrome.3’4
to be acute
ment,4
others
moid
reactions.3
taneous
not
While
leukemia
contend
are
mechanism
but
with
15.9
g/dl,
conditreat-
transient
leuke-
be related
cells
neous
cytogenetic
Serial
provided
resolution
studies
useful
information
about
of this child’s
disease.
types
the
3% lymphocytes,
platelet
count
was
3%.
Cytogenetic
technique
studies
by
PHA
stimulation.
grown
from
Since
newborns
he was
netic
analysis
marrow
after
trypsin-Giemsa
biopsy
33-51
banding
A
in
para
white
Hospital
IV,
mother
aborta
0),
circumcision.
blasts
SJCRH
that
day
The
resembled
for further
Blood. Vol.
boy
was
Five
patient’s
fibroblasts
for
From
and
a 24-yr-old
the
was
no
blood
excessive
count
myeloblasts.
was
The
St.
Jude
of acute
white
and
group
bleeding
160
(gravida
delivery
incompatibility
blood
patient
Children’s
x
a diagno-
that
below
the
from
blood
biopsy
and
cells
incubated
with
and
was
and
the
done
analysis.
findings
Since
these
leukemoid
patients,
the
red
cells
were
or infection,
as hemorrhage
blood
no
developed
packed
with
such
for
in all
thrombocytopenia
Transfusions
2 mo,
value
21
the cytogenetic
in
all
acetabular
mean
syndrome.
spontaneously
Anemia
were
the
chromosome
normal,
Down
Down
features.
trisomy
for later
had
have
dermatoglyphics
except
a skin
phenotypically
patient
Within
the
counts
had
V,
were
was
developed
109/liter
with
was then
referred
of
part
Program
Foundation,
Submitted
Address
by
Center
October
reprint
returned
to
Clinical
Project
60%
to
North
332
©
I 980
March
of
Cancer
Education
(CORE)
Si.
of Pediat-
Tennessee
1979:
P.O.
& Stratton.
and
accepted
to Garrett
St.
Grant
CA-20180.
ofDimes.
requests
Lauderdale,
by Grune
Pathology.
Department
University
Grant
of Hematology-Oncology.
after
the
Center
Tenn.
Support
/6.
and
and
Genetics,
Memphis.
in
Cancer
National
Hospital,
Medical
Sciences,
Leukemia
done
ofllematology-Onco/ogy
‘s Research
Section
23944.
or
count
Divisions
Children
Supported
myeloblastic
woman
labor,
A complete
when
leukocyte
Jude
Box
CAthe
from
the
by AISAC.
19. 1979.
Brodeur.
Children’s
318,
a grant
December
M.
Grant
CA-21765,
Memphis.
M.D..
Research
Tenn.
Division
Hospital.
38101.
Inc.
0006-4971/80/5504-0024$0I.00/0
evaluation.
55, No. 4 (April),
to
pregnancy,
infection.
of life
rics,
referred
stains.
of the
for the chromo-
f or Health
for evaluation
later,
complications,
develop.
and
disclosed
cultured
month.
first
with
frequently
deviations
resolve
but other
and
esterase
consistent
normal
and in all cells
was given.
the
not
feet,
also
days
sometimes
chemotherapy
50%
myeloblasts
cytoge-
modification
was used
conditions
count
for the characteristic
analysis
were
the
myeloblasts.
with
specific
leukemia
hands,
he was
that
were
19%
reticulocyte
hypercellular
and
carefully
17#{176}-2 standard
marrow
during
acute
were
PHA.
did
Fibroblasts
with
the bone
Black,
of
with
70%
the
resembled
findings
examined
without
l09/liter
and
was
that
was consistent
a hemoglobin
x
and
an enlarged
leukemia.
Chromosome
required,
REPORT
was
was
There
of congenital
on his second
for 72
according
cytologic
appearance,
newborns.
Jude
(SJCRH)
His
uncomplicated.
evidence
Whang.6
harvested
A
culture.
and
done
of all preparations.
3-day-old
leukemia.
and
and
of Seabright7
CASE
Research
of Tjio
specimen
days
technique
(PHA)
were
studies
were
cells
Sudan
Radiographs
from
of the
lymphocytes
phytohemagglutinin
Bone
a skin
of blood
and
136
l09/liter
aspirate
primitive
syndrome,
suggested
a modification
with
done
of the technique
to a modification
were
were
marrow
myeloblastic
facial
x
and
An erythematous
included
of
was in
an enlarged
extremities
8% eosinophils,
242
peroxidase,
clinical
angle
METHODS
et al.5 Cultures
without
overnight
hr with
some
of blood
of Moorhead
incubated
AND
bone
The
with
These
was
margin,
data
count
and
included
margin.
lower
and
a leukocyte
neutrophils,
normal.
sponta-
chest,
Laboratory
The
The
of
face,
costal
left costal
the
appearance
findings
the right
below
toxicum.
and
Although
MATERIALS
5 cm
on the
sis of acute
Down
normal
of several
rash
reacted
to an
in some
patients
with
is exceedingly
rare
in
papular
physical
4 cm below
replacement
for spon-
Abnormal
palpable
in infants
newborns.
We present
a phenotypically
normal
infant
with trisomy
21 mosaicism
who had a transient
leukemoid
reaction
that
resembled
acute
myeloblastic
leukemia.
palpable
erythema
these
without
may
liver,
spleen,
with
responsible
is unclear,
abnormality
since
it
of
he had a normal
to SJCRH,
distress.
that
but
consider
remits
they
type
no acute
Conditions
leukemia,
unusual
some
that
that
The
resolution
inherent
syndrome,
are
On admission
frequency
In contrast
1980
691
From www.bloodjournal.org by guest on June 14, 2017. For personal use only.
BRODEUR
692
Ta ble 1 .
Cyto
Data
genetic
Patient
Percent
Age
Tissue
Cells
(days)
Sampled
Counted
Blasts
of Cells
patient
had a small
percentage
with an abnormal
karyotype
Counted
47.XY.
46.XY
3
Blood
50
70
0
100
3
Marrow
22
50
0
100
clone disappeared
fulminant
acute
21
±
2-yr-old
of bone marrow
(48,XY,+2l,+C).8
spontaneously
but
leukemia
developed.
who
had
ET AL.
an
cells
This
reappeared
The other
abnormal
when
was a
clone
(59,
at age 2 in addition
to the
trisomy
21 karyotype;
cytogenetic
studies
were
not
done during
the neonatal
period.9
There
is only one
report
of transient
spontaneous
remission
of acute
+4C,+3D,+E,+2F,+3G)
8
Blood
8
Skin
50
80
0
100
NA
96
100
Blood
75
0
76
100
Marrow
34
9
100
100
4
24
0
Not applicable.
normal
and
genetic
the
study
child
had
organomegaly
had
of cultured
mosaicism
diminished.
fibroblasts
for
trisomy
that
Based
were
21 (47
on the
obtained
trisomic
cyto-
earlier,
and
96
the
By
the
time
he
The
count
leukocyte
lymphocytes,
blasts.
24%
767
had
the
I
normally.
bone
).
8800
x
was
At
analysis,
mo of age.
9
the
marrow
x
with
50%
request.
9.4
all
almost
g/dl
and
After
40%
and
72-hr
no
PHA
karyotype,
and
marrow
cells
34 bone
had
the
neutrophils,
1% basophils,
lOt/liter.
Only
and
a normal
karyotype
and developing
to be healthy
he appeared
parents’
was
had a normal
karyotype.
for
had
organomegaly
time
eosinophils,
406
lymphocytes
47,XY,+21
At
the
that
l09/liter
2
count
of blood
satisfactory
(Table
and
was
platelet
stimulation,
old,
at
7% monocytes,
The
were
3 mo
was
hemoglobin
chromosome
analyses
of
blood
not done.
were
DISCUSSION
The
leukemoid
transient
acute
leukemia”
well recognized
in patients
but poorly
reaction
ly”
the hematologic
in 21. Resolution
Down
syndrome
tion when
they
of this transient
but
it
poiesis
resolved
occurred
“spontaneousin 4 children
with
who developed
the leukemoid
condiwere I mo to 3 yr old. The mechanism
leukemoid
reaction
is not understood,
indicate
ineffective
to delayed
maturation
may
due
is a
In
Down syndrome
who had
features
of acute
leuke-
disorder
also
“transient
with Down syndrome
understood
phenomenon.
a review
of 56 newborns
with
the clinical
and hematologic
mia,2
or
regulation
of the
incubated
although
puzzling,
proliferation
normal
cells).
disappeared.
leukemia
in a phenotypically
normal
this patient
had a normal
karyotype.13
In our patient,
all of the cells from
PHA
had
the
blood
47,XY,+21
bone marrow
by myeloblasts.
may indicate
samples
karyotype,
should
present
was
the
and
have
been
found.
in all cells from the
when only 50% of it had been replaced
The
absence
of normal
karyotypes
that
the proliferation
of trisomic
cells
suppressed
production
of the cytogenetically
cells. Within
3 mo, this apparent
proliferative
tage was lost. Cells with a normal
karyotype
dominant,
and
myeloblasts
disappeared
blood.
Also, none of the trisomic
marrow,
although
the percentage
was still slightly
increased
(9%).
In about
leukemia,
and
only 70% were myeloblasts.
This finding
since
the PHA
should
have stimulated
of thymus-derived
lymphocytes,
some
normal
karyotypes
Similarly,
trisomy
21 was
half of the
the malignant
normal
advanbecame
from
the
in the
cells persisted
of marrow
cases
of acute
cells
have
blasts
myeloblastic
an abnormal
karyotype,
and gain, loss, or rearrangement
of chromosome
21 occurs
with increased
frequency.14
At first
it was not clear
whether
the blood
and marrow
cells
with trisomy
21 in our patient
represented
a malignant
clone
studies
of myelomyeloid
and
with
newborn,
or his “normal”
of skin fibroblasts
mosaicism
had
for
trisomy
a leukemoid
somatic
cells.
However,
indicated
that the child
later
had
21.
child
reaction
It is likely
involving
that
the
this
trisomic
cells
other
bone
marrow
elements.2’3
Also,
some
of these
children
may have a physiologic
stress
produced
by
associated
conditions,
such as blood group incompatibility,
infection,
or heart disease,
that may stimulate
an overreaction
of the myeloid
elements
in the bone
that subsequently
were replaced
by cells with a normal
karyotype.
Mosaicism
for trisomy
21 may be the basis
for the transient
leukemoid
reaction
in some newborns.
This may also apply
to newborns
who are phenotypically normal,
as was the case for our patient.
marrow.
In the English
literature
there are nine case reports
of cytogenetic
studies
in newborns
with
Down
syndrome
who had spontaneous
resolution
of a condi-
Serial
cytogenetic
analysis
should
guish between
congenital
acute leukemia
leukemoid
reactions
in newborns.
newborn
suspected
of having
leukemia
tion indistinguishable
these
nine patients
still free of disease
cytogenetic
analysis
of blood
spective
of the phenotype,
should
warrant
chromosome
he was
autopsy.
again
8 mo
The
when
old
last
they
from acute
had a 47,+G
1 .5-4 yr later.
and
two
were
had
leukemia.4’8’2
Six of
karyotype
and were
Another
died when
no evidence
patients
about
of leukemia
developed
2 yr old.
at
leukemia
At
birth,
one
blasts
to check
for
mosaicism.
not
be given
chemotherapy
progresses
despite supportive
help to distinand transient
Further,
any
should
have
and bone marrow.
Irrefindings
of trisomy
21
analysis
of skin
fibroThese
unless
treatment.
patients
should
their
disease
Patients
with
From www.bloodjournal.org by guest on June 14, 2017. For personal use only.
LEUKEMOID
REACTION
TRISOMY
a normal
karyotype
types
other
than
treated,
since
is remote.’3
the
693
2 1 MOSAICISM
and those
with abnormal
karyotrisomy
21 probably
should
be
likelihood
of spontaneous
resolution
Hungerford
DA:
from
peripheral
human
6. Tjio
JH,
cells
without
tion.
Stain
Chromosome
Whang
prior
somes.
ACKNOWLEDGMENT
We
and
are
to Jane
grateful
to Dr.
Seifert
Alvin
for reviewing
8.
M.
Mauer
for
this
manuscript.
helpful
Lancet
9,
F,
and acute
Conen
PE,
AmiDisChild
10.
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Am
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1980 55: 691-693
Transient leukemoid reaction and trisomy 21 mosaicism in a phenotypically
normal newborn
GM Brodeur, GV Dahl, DL Williams, RE Tipton and DK Kalwinsky
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