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Acute
Leukemia
Irradiation
for
By Richard
During
a 5-yr
leukemia
in the metropolitan
patients
who
radiation
Glyn
surveillance
study
had
City
previously
for
Localized
Carcinoma
K. Karchmer,
Kansas
therapy
Following
area,
and
nificant
ir-
of
larynx
developed
acute
leukemia.
frequency
of occurrence
represents
G. Caldwell,
four
received
carcinoma
of the
the
Tom D. Y. Chin
increase
of
the
expected.
These
even
such localized
with
possibility
The
a sig-
Larynx
must
ions.
be considered
Hodgkin’s
may
and
therapy
described
the
for malignancy
creased
localized
development
in four
frequency
neoplasms,
population
implied
that
affecting
acute
of
was
Patients’
names,
rooms
certificates.
period
asked
the
tumor
A physician
the data.
These
January
to complete
of
records
543
1966 through
a questionnaire
of a previous
malignancy
patients
were found
with
had
received
these
four
irradiation
Therefore,
it was
the
May
21.
November
Richard
Utah
Glyn
G.
84/
Chie/
(EIP):
currently
/973.
these
recently
infor
the
chart
diagnosed
with
one
The
of
the
Auguci
death
to obtain
and
verify
leukemia
during
(enter
or
/or
the
a relative
about
the
therapy.
all four
and
hospital
was
his-
records
authors
on
(R.K.K.).
In-
leukemias
and laryngeal
during
the
5-yr
period.
probability
(EIPi.
and
hospital
and
received
irradiation
of the larynx.
neoplasms.
by
durarea.5
from
physicians.
hospital
the
Program
revision
obtained
numbers
of acute
Kansas
City
area
Education,
first
were
patient
had
of carcinoma
to determine
Health.
M.D.:
Oncology
b; Grune
Vol. 43, No.
Medical
to Dr.
& Stratton.
1974
Medicine.
of these
l)isea.se
patients
(‘ontrol.
repre-
Pub/ic
Health
We//are.
8.
1973.
second
(‘enter
A (tiiities.
Ecology
University
Oncology
Program.
Teratology
of Human
requests
in
Epidemiologist.
Epidemiology
and
Professor
5 (May),
Resident
M.D.:
12:Jormenl;’.
Kansas
City.
Address
reprint
Blood,
of
al.4
revision
5,
‘sove,,,her
1973,
ac-
6, /973.
CaIdwell,
formerly.
c /974
0/
K. Karchmer,
City.
et
data
collected
Kansas
City
1970. The patient
included
information
again
total
Investigations
Department
Submitted
cepted
possible
Feological
for
reviewed
was available
on the
in the metropolitan
U.S.
patients
therapy
were
each
or if the
a history
the
of practicing
December
which
formation
carcinomas
From
a complication
localized
radiotherapy
report
suggested
an
reviewed
metropolitan
leukemia,
reviewed
tory
Four
Service,
well
A
in
given
high-dose
irradiation
could
be made
because
have
in the
diagnosis
included
patients
we
registries,
then
data
decis-
been
reports.”2
of leukemia
Poth
following
this last
the
leukemia
unknown.
with
and
radiotherapy,
has
be
disease.
in patients
conclusions
Because
of the above
implications,
ing the first 5 yr of leukemia
surveillance
record
this
of acute
leukemia
patients.
Although
of acute
leukemia
no statistical
at risk
leukemia
survivors
the
that,
in therapeutic
irradiation
Commission
occurrence
disease
over
indicate
of irradiation-induced
CUTE
AND
CHRONIC
leukemia
following
documented
by the Atomic
Bomb
Casualty
recent
study
by Chan
and
McBride3
reviewed
the
irradiation
observed
findings
and
EIP.
Medicine.
for
(‘DC.
o/ Utah
and
Medical
Teratology
Disease
Tom
University
(‘ontrol.
D.
Salt
(‘enter.
.4ctiiities.
Atlanta,
Y. Chin.
of Kansa.s
Lale
EIP.
(‘D(’.
Ga.
30333:
M.D.:
Medical
Director,
Center.
(‘a/dwell.
Inc.
721
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722
KARCHMER,
senting
an excess
geal
over
carcinoma
the
expected
to develop
number
No.
of irradiation
patients
AND
with
CHIN
laryn-
leukemia.
(See Table
PATIENTS
Patient
CALDWELL,
1)
I
This 74-yr-old
white
male entered
the hospital
in February
1967 with a 2-mo
history
of hoarseness. Laryngoscopy
showed
a tumor
of the right
true vocal
cord.
Multiple
biopsies
revealed
welldifferentiated
squamous
cell carcinoma.
A complete
blood
count
(CBC)
was normal.
He received
6000 rads tumor dose with 60 Co to the larynx
over
a 6-wk
period.
In August
1967.
a second
laryngoscopy
and
no more
the
patient
count
cytic
origin.
Auer
rods.
fection
(WBC),
The
and
Patient
family
died.
No.
This
right
to the
to
white
and
the
right
laryngeal
node
neck
area.
left
1967,
of his
WBC
cancer,
but
of 25,300/cu
when
mononuclear
died
cells
aspiration.
hospital
cell
found
to
At this
time,
the
and
Many
of
the
squamous
was
neck
of respiratory
This
g/I00
7.7
was
blasts
of
patient
and
1967.
extending
into
the
and
his
weaker.
hematocrit.
2l’:
and
white
or
mono-
myelocytic
ratio,
The
surgery,
December
became
ml:
being
In
now
rapidly
nuclear-cytoplastic
marrow
of the
of the
failure,
of a recurrence
He
contain
tumor
CBC
was
and
multiple
nucleoli,
developed
latter
cells
with
and
an
were
the
and
a respiratory
of his laryngeal
was
He
One
in-
blasts.
ml.
bone
Auer
was
performed.
3000
rads
with
health
no
good
evidence
of
a hematocrit
of
27%
lymphocytes.
study
death
there
until
recurrence
27%.
and
a
and
35%
showed
months
a markedly
later
the
was
no
patient
obvious
neoplasm.
No. 3
83-yr-old
white
Laryngoscopy
and
Ta We 1.
Patien
male
biopsy
entered
revealed
ts With
Acute
the
hospital
that
the
left
Le ukemia
in April
cord
Fol lowing
1969
was
with
infiltrated
Irradiation
a 6-mo
by
history
squamous
of
hoarseness.
cell
carcinoma.
f or Carcinom a of the Larynx
Dat.
Amount
#{176}Co
Therapy
Patisnt
No.
Tumor
B.gun
ma.
yr.
2
1967
1
Neck Area
Treated
Bilateral
Port
Size
Dose
(cm)
(rads)
6 (diam)
6068
Marrow
Dose
(rods)
of
Marrow
Irradiated
with
Midcervicol
rondo
spine
200
Date
Leukemia
Diagnosed
ma
yr
Latent
Period
(mo)t
5
1968
15
4
1967
48
Phantom
2
4
1963
Right
C2-7
3000
lateral
post
laryngectomy
3
4
1969
Bilateral
5 x
5
6000
4
10
1967
Bilateral
4 x
4
6000
eEstimate
tTim.
by radiotherapist
between
irradiation
treating
and
patient.
onset of leukemia.
600
a
Co
metastasis
a
in
true
and
was
Six
At
the
he developed
marrow
rods.
of
laryngectomy.
He
There
The
of
not
later
hoarseness.
portion
received
year
8.6 g/l00
granulocytes,
of
anterior
then
dissection.
of appetite.
of
mature
complaining
the
a wide-field
cells.
presence
autopsy
1963
of
underwent
neck
loss
a hemoglobin
bands,
33%
April
normal.
radical
weakness
myeloblasts
in
carcinoma
epiglottis.
underwent
his CBC
showed
mm.
with 5%
cells.
Patient
he
refused
normal.
which
1968,
40#{176},,
of the
increased
entered
he developed
number
evidence
tumor,
May
patient
was
performed.
revealed
surface
in the
April
increased
male
biopsy
lymph
a node
the
The
CBC
2
64-yr-old
jugular
was
In
with
an
a bone
autopsy
cords.
hemoglobin,
mm,
showed
refused
No
Laryngoscopy
cord and
cells
both
A second
of
airway.
following:
120,000/cu
blast
given.
excision
his
the
of
safely
blocking
showed
The
been
intralaryngeal
and
admission
on
involvement
have
an
commissure
blood
revealed
could
underwent
anterior
CBC
biopsy
irradiation
C4,5,6
12
1970
20
C4,5,6
6
1968
9
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ACUTE
He
LEUKEMIA
then
this
received
6000
rads
to the
larynx
his
CBC
was
normal.
In
ml,
a hematocrit
of 24.7,,
granulocytes,
3”,,
Indirect
laryngoscopy
bands,
therapy,
of 7.7
g/lOO
mature
forms.
70
blast
no
palpable
nodes.
bleeding.
His
developed
the
in
723
December
vocal
cord,
were
Patient
No. 4
This
throat.
and
but
sepsis
showed
present
white
male
were
palpable,
of47’,,
and
a WBC
lymphocytes.
squamous
cell
treatments
over
a 6-wk
breathing.
unchanged,
vealed
90,,
period.
A residual
Both
the
pathologist
and
the
cells
in the
patient’s
leukemic.
Two
stantiated
the
above
the
admitted
with
His
autopsy
did
of regional
liver,
the
his
hospital
CBC
with
10,,
patient
in
was
mature
he
mm,
with
and
5’
there
were
and
intestinal
of
lower
13,400/cu
Poorly
differentiated
mm.
tumor
He
remaining
leukemic
that
vocal
with
was
these
died
of
60
glottis.
and
The
to
89”
the
CBC
sore
mature
biopsy
showed
larynx
because
His
a
a hematocrit
of
was
in
30
difficulty
essentially
A bone
marrow
aspiration
reand exhibited
multiple
nucleoli.
immature
lymphocytes
1967.
a
Co
and
ml,
bands,
cord.
performed
the
October
hoarseness
16 g/lOO
1%
left
rads
across
of
with
of
was now
present.
large
and immature
smear
later
the
6000
growing
fet
peripheral
cu
some
1967
a tracheotomy
found
2,400
reveal
granulocytes,
of
received
hematologist
months
October
a hemoglobin
lesion
l968,
to
spleen.
showed
a polypoid
of
Prior
a hemoglobin
2,,
monocytes,
neoplasm.
and
a WBC
metastasis.
and
period.
with
hemoptysis
died.
lymphadenopathy
many
ofwhich
were
from
lymphocytic
was
a 7-wk
a WBC
later
In June
tumor
but generalized
lymphocytes,
he
marrow,
the
and
with
mm,
and
platelets,
forms.
revealed
carcinoma,
over
pancytopenic,
blast
and
of3I,800/cu
was
52’,,
entered
Laryngoscopy
he
basophils,
41#{176},,lymphocytes,
no evidence
of recurrent
evidence
bone
79-yr-old
in 30 treatments
1970,
showed
and
no
in the
No
nodes
now
60 Co
decreased
2,,
revealed
1970,
smear
pneumonia
infiltrates
with
In
peripheral
with
November
He
respiratory
was
were
classified
infection.
different
as
An
an
acute
autopsy
sub-
diagnosis.
DISCUSSION
Each
of the
irradiation
leukemia.
four
four
patients
described
to a small
area
of the
Each
had well-documented
patients
of leukemia
had
a normal
in patient
CBC
1 was
in this
head
study
received
a large
amount
and
neck
and
later
developed
carcinoma
of the larynx.
Three
before
determined
receiving
from
the
radiotherapy.
blasts
in the
The
of
acute
of the
diagnosis
peripheral
smear
and the presence
of Auer rods in these blasts.
Patient
2 was diagnosed
from
the
bone marrow
aspiration.
At autopsy,
patient
3 had acute
leukemic
infiltrates
in
several
organs.
Patient
4 almost
certainly
had chronic
lymphocytic
leukemia
prior
to this therapy
and the bone
marrow
previous
however,
then
predominant
cell
of whether
leukemia,
a
and
blast
they
quite
The
change
rare.
following
treatment,
showed
many
immature
type.
McPhedran
phase
occurs
during
concluded
a true blast
in the
blood
and
Heath6
picture
in patient
no
tissue
types
were
chronic
does
4 could
known
natural
the
not
have
question
lymphocytic
exist
or
been
not
mentioned.
Our
four
is
secon-
predisposition
four patients
who received
high-dose
prior
to developing
acute
leukemia,
of these patients
had received
his therapy
for carcinoma
study
by Lathropt
of supervoltage
irradiation
for
seven of 12 stage-I
patients
who died of other
diseases
The
reviewed
changed,
from
the
many
studies
done
on carcinoma
of the
leukemia
as a significant
complication.7’8
ever, Poth et al.4 have described
therapy
for various
malignancies
cancer.
blood
picture
cells
different
the course
of
phase
probably
dary to the irradiation
therapy
he received.
Patients
with carcinoma
of the larynx
have
to developing
leukemia.
The
have not specifically
mentioned
his
larynx
How-
irradiation
and one
of the larynx.
Also,
in a
carcinoma
of the larynx,
died of another
primary
patients
had
no
obvious
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
724
KARCHMER,
immunologic
or hereditary
veloping
leukemia,’#{176} and
to the onset
ofthe
defect
which
would
none of them
received
CAIDWELL,
AND
have
increased
the risk
any cancer
chemotherapy
CHIN
of deprior
leukemia.
Thus,
the development
of leukemia
in these
four cases of laryngeal
carcinoma
seemed
unusual.
The four patients
received
a minimum
of 3000 rads of localized
radiotherapy
(see Table
I ), the one obvious
leukemogenic
factor.
The average
latent
period
irradiation-induced
of
can
radiation
influence
23
mo was
leukemia:i2
shorter
than
previously
described
for apparent
however,
age, sex, dose,
and area
of exposure
leukemogenesis.H
The
four patients
was 75 yr. which
is later
laryngeal
carcinoma.
Furthermore,
received
irradiation
responsive
(see
Table
1 ), but
vertebral
three
of these
four patients
over the 5 yr (1966
1970)
of these
three
cases
could
first
pathology
participating
surveillance
in the
carcinoma
and
were
leukemia
of the
of diagnosis.
larynx,
carcinoma
Kansas
veloped
method
collected
are,
type
have
from
therefore,
285
of therapy
(e.g.,
285
with
patients
was
in these
most
cellular
and
the date
occurrence
date
or
carcinoma
both).
of
and 12,, were
age-adjusted
the
females,
rate
for
to the 1970 metropolitan
be expected
to have
deThe 285 patients
in this
to the
161 patients
of the
nonirradiation
the
age-sex
specific
therapy
cases thus
all patients
diagnosis,
collection.
None
Applying
of irradiation
of three
stat&3
would
5-yr period.
irradiation
Cityi#{244}to the age-sex
distribution
0.07 patients
would
be expected
The record
35 hospitals
to report
cell
males
annual
York
Thus,
1970.
same
radiotherapy.
squamous
a complete
reported.
pathologic
were
the
101 received
not
asked
sex,
surgery,
88#{176}
of these
yr. Applying
with
cases,
irradiation.
leukemia.
Kansas
mately
is the
were
age,
of treatment
consistent
reported
received
acute
marrow
study
their
of the larynx
in 1960
in New
City
population,i4iS
310 individuals
carcinoma
of the larynx
over the
Of the
the
at diagnosis
diagnosed
during
1966
departments
of the
giving
larynx
during
the 5-yr period:
with
the mean
age being
61
study
age
received
irradiation
and
then
developed
of the leukemia
study,
the statistical
sigbe determined.
Data
were
collected
from
all cases of laryngeal
carcinoma
rooms,
tumor
registries,
and
Data
mean
the mean
age usually
observed
in
small
areas
of cervical
marrow
in the elderly.i2
Since
leukemia
niticance
with
than
only
larynx.
had
patients
rates
for
and
have
acute
of the 161 reported
to have developed
acute
to the end of the study
represents
a significant
ln 60 cases,
cancer
could
developed
leukemia
in
cases,
approxileukemia
from
in December
1970. The
increase
of the observed
over the expected:
the probability
of as many
as three cases occurring
by chance
isp < 0.001
(Poisson
distribution).
This study
suggests
a definite
increased
incidence
of acute
leukemia
following
irradiation
for even small,
localized
neoplasms
in which
the bone
marrow
may
be affected.
Previous
dose,
the
However,
studies
temporal
are
and
epidemiologic
difficult
spatial
by the
marrow,
because
distribution
surveys
xraysilit
and radiotherapy’9’2#{176}
thesis
that
the risk of leukemia
absorbed
to compare
of
of
the
increased
of differences
dose,
leukemia
and the cases
presented
induction
is proportional
irrespective
of the
volume
and
here
of marrow
in irradiation
patient
from
support
to the
selection.
diagnostic
the hypototal
energy
involved.’9
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
ACUTE
725
LEUKEMIA
Patients,
of the
patients
especially
larynx
who
change
recurrence
in
portance
the
may
have
elderly,
receiving
have
an increased
received
irradiation
their
clinical
status
must
of their
original
neoplasm.
of epidemiologic
treatment
irradiation
therapy
risk of developing
must
be adequately
not
surveillance
automatically
This
study
carcinoma
therefore,
and any
be assumed
emphasizes
also
for recognizing
for
leukemia:
followed,
causes
and
to be a
the
im-
effects
in any
program.
ACKNOWLEDGMENT
Mark
Devine,
report
their
M.D.,
patients.
Oscar
John
Pinsker,
Mellman
M.D.,
and
assisted
in the
Robert
L.
statistical
Rogers,
M.D.,
gave
permission
to
analysis.
REFERENCES
Bizzozero
I.
OJ Jr. Johnson
Radiation-related
leukemia
Nagasaki,
and
1946-1964.
appearance
KG.
in
Ciocco
A:
Hiroshima
and
I. Distribution,
incidence
N
274:1095,
time.
EngI
J Med
CC
(ed):
2. Bizzozero
Kawasaki
OJ Jr. Johnson
5,
leukemia
Toyoda
in
1964.
II.
kemia,
5:
Hiroshima
Observations
survivorship,
Ann
Intern
3.
Chan
disease
66:522,
BWB,
and
and
Nagasaki,
on
type-specific
1946leu-
clinical
behavior.
JA:
Can
Med
J
JL,
SL:
lowing
Med
5.
George
Acute
localized
128:802,
1971
Caldwell
GG.
Mellman
14.
106:
Arch
Silberfarb
TDY:
I. Incidence
data.
McPhedran
P.
7.
occurring
of the
8.
Heath
Am
chronic
J NatI
11.
changes
S.
Acute
lymphocytic
therapy
in
Radium
R:
for
Cancer
Proukakis
General
S.
of
Otol
Rhinol
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Jr.
leukemia:
Inst
following
Lindop
Epidemi-
observations.
1967
PJ:
irradiation,
in
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1962,
Census:
Census
of
Char-
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the
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Rowse
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study
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of
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GG.
RK.
Census
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TDY:
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RE,
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Incidence
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From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
1974 43: 721-725
Acute Leukemia Following Localized Irradiation for Carcinoma of the
Larynx
Richard K. Karchmer, Glyn G. Caldwell and Tom D. Y. Chin
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