Download Serum Lactic Dehydrogenase (LDH)

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Serum
Lactic
Dehydrogenase
Marked
(LDH)
Elevations
Serum
total
lactic
dehydrogenase
leukemia.
mean
range
while
that
of patients
range
was
i26-684
(26.8%)
with
of serum
with
acute
the
i9
case
levels
between
L
the
crisis
during
and
are
a range
LDH
values
ANLL
and
levels
different
are
cell damage,
A relationship
LDH
levels
workers,
in
Elevated
tissues
LDH
as well
both
of
and
statistically
of ALL.
were
levels
as in
lU/liter.
that
in individual
exists
animal
encountered
serum
of
tumors.
tumor
not
0.001 ).
the
in 42 patients
with
cate that LDH
cases of acute
levels are moderately
leukemia,
irrespective
the
but
studied
acute
Serum
until
LDH
Nineteen
Burkitt’s
leukemia
ANLL
(20
et
crisis,
for the
ALL
(mean
admission
started.
Blood.
to the
In four
Vol.
56,
hospital
patients
and
non-Hodgkin’s
and
multiple
ALL,
lymphoma,
myeloma
(iron-deficiency
idiopathic
and
thrombophlebitis)
liver
damage
cases
of acute
ries
(ALL
and
cytochemistry,
markers
and
levels
and
in
1980
leukemia
lupus
The
(CLL),
nonmalignant
erythematosusaplastic
signs
anemia,
of hemolysis
and
series.
in the
peroxidase,
sudan
paranuclear
acid
diagnosed
ifcells
esterases
and
phosphatase.
black,
and
A
proportion
surface
ALL
of
markers:
red
ALL
FC
while
surface
some
black,
or
were
C3
0.
In
for
positive
0.
sudan
red
negative
were
red
sudan
inhibition,
oil
were
oil
receptor,
stains
fluoride
PAS,
cases
cell
(PAS),
and
and
0,
catego-
microscopy
by
Schiff
if cells
for either
oil
main
cytochemical
without
PAS.
for
cases
phosphatase,
esterases,
positive
two
of light
acid
and
as
phosphatase,
were
following
acid
classified
negative
difficult
The
with
esterase,
into
basis
more
periodic
esterases
were
classified
on the
for
ANLL
was
peroxidase,
paranuclear
or
acid
examined
for
receptors,
the
surface
are
method
determined.
were
primarily
and
peroxidase,
Hospital
were
I 7-77
yr).
Hodgkin’s
with
with
this
ultrastructure.3233
cases
following
leukemia
ANLL),
performed:
general,
METHODS
isoenzymes
LL group
34
in
of age
of Leukemia
nonspecific
chemotherapy
from
range
malignancies:
systemic
I2
6 of them
(mean
patients
I). Cases
excluded
Classtfication
AN
yr
purpura-ITP,
(Table
were
chloroacetate
before
anemia,
had
leuke-
I I males,
lymphatic
30
thrombocytopenic
black,
the
and
with
patients
The
26 yr),
chronic
(MM),
acute
CML,
2 females).
with
As-D
on
with
(7 males,
with
monoblastic
leukemia;
9 patients
53 patients
in many
cell type.
in all cases
No. 3 (September),
of
2 patients
23
promyelocytic
examined
included
and
from
24-62
were
done
sera
group
mdi-
was
with
levels
number
patients
with
yr (mean
results
determination
2 patients
AML,
I I -70
The
to the
with
CML
leukemia.
according
42
was
levels
determined
and
the
LDH
LDH
the
including
and
LDH
LDH
in
ALL,
yr),
material
the
Department
and
Hebrew
day
of
Address
of
ofHematology.
was
of
Hematology,
Hadassah
University-Hadassah
Medical
University
School.
Jeru-
Israel.
Submitted
The
serum
with
group
serum
elevated
of their
assayed
had
with
were
46
control
salem,
al.3’
while
in serum
elevated
8 females),
I patient
blastic
All
with
Assay
Morgensten
crisis.
differences
(1 1 males,
In addition,
total
AND
were
myeloid
now,
and
in blastic
crisis
of chronic
but not in any of the patients
with
leukemia
(ANLL).
These
results
levels
In 1 5 of
chronic
lymphoblastic
The
Patients
lU/liter).
with
the
in 6 cases
lU/liter.
1038
correlated
were
patients
patients
and
From
LDH
(ANLL).
and
900
+
3 patients
were
levels
leukemia.
SLE,
In
with
to correlate
suggest
that markedly
elevated
serum
more indicative
of ALL than ANLL.
Serum
over
The
lU/liter,
Material
disorder
30
However,
markedly
elevated
levels
were
recorded
the
majority
of patients
with
acute
Iymphoblastic
Enzyme
levels
chronic
1 13
leukemia
markedly
levels
±
313
lymphoma
of 1669
as ALL.
that
LDH
with
disorders.
and
with
had
regarded
It appears
Patient
yr
between
of solid
elevated
but
shown
we have
a
non-Hodgkin’s
mass,2029
been
MATERIALS
had
value
3 patients
not
patients.
lU/liter
In addition.
of these
was
females).
in neoplastic
patients
with
In
Recently,
leukemia
(ALL)
myeloid
leukemia,
acute
nonlymphatic
patients
One
but
210
(1 1 .3%)
(mean
lU/liter.
9 patients
nonlymphoblastic
patients
lU/liter
mia,
tumors.’’9
Burkitt’s
lymphoma,22#{176}
elevated
in many
patients,
and
In acute
of these
900
to
LDH
levels
have
frequently
been
observed.22’
addition,
there
appears
to be a good correlation
levels have
of leukemia.
in
subsequent
there does not appear
to be a good correlation
increased
LDH
levels
and
specific
types
tumors.
In animal
and
human
leukemias,
elevated
the type
(p <
significant
and
and
and
are
the
particularly
levels are
activity
above
prednisone.
(LDH)
systems,
human
disease
None
leukemia.
lymphoproliferative
402 ±
was
In 6 of the
of 402-3582
serum
LDH
levels
may
be
between
neoplasia
and
has been
reported
by many
epithelial
lymphoma,
serum
LDH
lU/liter.
acute
other
relapse.
cell
tissue
or
elevated.
increased
500
with
and
± 74 lU/liter.
308
of 970-1940
DEHYDROGENASE
many
variety
had
to vincristine
suggestive
remission
ACTIC
above
(ALL)
patients
lymphoma
± 146 lU/liter).
were
had
clinically
was
Polliack
lymphoma
non-Hodgkin’s
disorders
serum
with
Leukemia:
Leukemia
Aaron
in 42
patients
of 413
levels
ALL.
and
and
examined
53
value
leukemia
with
Kornberg
were
and
in Hodgkin’s
(mean
in blastic
ALL
levels
crisis,
nonmalignant
LDH
responded
leukemia
blasts
levels
with
(78.9%)
(CML)
second
in blastic
lU/liter
ANLL.
patients
in acute
LDH
lymphoblastic
leukemia
(LDH)
6 of them
in Acute
in Lymphoblastic
By Abraham
myeloid
Levels
© /980
February
reprint
20. 1980;
requests
Hadassah
by Grune
accepted
to Aaron
University
& Stratton.
April
Polliack.
Hospital,
23. 1980.
M.D.,
Jerusalem,
Department
Israel.
Inc.
0006-4971/80/5603-01Y33$0I.0O/0
351
From www.bloodjournal.org by guest on April 28, 2017. For personal use only.
352
KORNBERG
Table
1 . Range
and
Mean
Values
o f Serum
LDH in 1 25 Patients
Leukemia.
Lymphoma.
and Nonmalignant
Range of Serum
LDH Levels (lU/Liter)
Mean ± SD Serum
LDH levels (lU/Liter)
19
402-3.582
1.669
±
ANLL
23
126-684
413
±
Hodin’sdisease
15
226-898
402
±
Non-Hodgkin’slymphoma
23
1.038
146
160-590
313
±
210
113
CLL
9
254-444
335
±
69
MM
6
184-488
317
±
114
30
180-491
308
±
74
Iron
disorders
deficiency
5
Thrombophiebitis
8
Aplastic
4
anemia
SIE
6
ITP
7
immunoglobulin,
sera.
In some
were
performed
analysis
anemia
was
E-rosettes,
cases,
and
T-antigen
transmission
to
done
assist
and
using
scanning
in definition
according
of
to Student’s
the
t
anti-I-cell
electron
cell
anti-
microscopy
type.
Statistical
test.
The
serum
LDH
and
I. The
normal
Hadassah
This
is
where
the
number
range of LDH
nizedinTable
The
levels
from
of
levels,
1.
the
range
the
cases
groups
are
patients
and
the
in each
mean
values
of
acute
shown
in
group,
the malignant
disonHodgkin’s
and
nona range
of LDH
levels
from
±
226
the
ane summa-
lU/liter
MM
liter.
of
in
was
total
serum
LDH
Hospital
is 100-500
the
nonmalignant
180-491
lU/liter
in
the
lU/liter.
disorders,
(mean
value
‘a
to
898
3000
LDH
(mean
levels
lU/liter).
value
were
210
lU/liter),
In all
and
413-146).
above
the
patients
In 6 ANLL
500
(78.9%)
the values
only 4 patients
the
Isoenzymes
and in all
were
levels
lU/liter
above
were
In 6
500
with
less than
500 IU/
LDH was 126-684
patients,
(543-684),
no patient
had levels above 900 lU/liter.
The
levels in ALL was 402-3582
lU/liter
(mean
1661 ± 1038 lU/liter).
In 15 of the 19 ALL
blastic
crisis,
while
type
but
responded
:D
402
the levels
were
the range ofserum
three
of the patients
metamorphosis,
the
970-1940
lU/liter).
A
2000
(mean
(588-898
and CLL,
In ANLL,
lU/liter
range
University
reflected
in all
control
was 308 ± 74 lU/liter).
Among
dens,
sena
from
patients
with
Hodgkin’s
lymphoma
displayed
160-590
(mean
313 ± 1 13 lU/liter),
respectively.
of the above
38 patients,
LDH
levels were above
RESULTS
leukemia
POLLIACK
Disorders
ALL
Nonmalignant
:i:
Acute
No. of Patients
Clinical Diagnosis
Fig.
With
AND
but
range
of
value of
patients
900 lU/liter,
while
below
500 lU/liter.
in
In
with CML,
all in acute
blastic
LDH
levels were elevated
(range
One ofthese
cases had a lymphothe
to
second
was
vincnistine
were determined
these
cases
both
in only
isoenzymes
undifferentiated
and
prednisone.
in
4 ALL
patients,
2 and 3 were
-
found
to be elevated;
however,
isoenzyme
3 was more
markedly
elevated
than isoenzyme
2 in these patients.
a
1000
There
is no statistically
serum
LDH
levels
among
leukemia
and the various
-
;t:- ;T
z<
1
-
LSCL
MM.
2,o
t,
I
02
O.
Z
Il
0
1-i
0
z
the absolute
number
ofcirculating
ALL blasts
and the
serum
LDH
levels (Fig. 2). This phenomenon
may be
explained
by the possibility
that elevated
serum
LDH
levels may relate
more to total leukemic
cell mass than
to the numbers
of circulating
blasts.
However,
in
individual
Fig.
disorders.
1
.
Serum
LDH
level
in
>
in the
ANLL
0.05).
However,
the differences
in LDH
levels between
the
ALL
patients
and all the other
groups
were statistically significant
(p < 0.001).
On initial
admission,
no correlation
existed
between
ODD
DO
;:
significant
difference
the patients
with
control
groups
(p
neoplastic
and
non-neoplastic
found
relapse.
patients
during
This
with
cytotoxic
is cleanly
ALL,
good
treatment,
demonstrated
correlation
was
remission,
and
in Fig. 3 and 4,
From www.bloodjournal.org by guest on April 28, 2017. For personal use only.
LDH
IN ACUTE
353
LEUKEMIA
0
ACUTE
LYMPHOSLASTIC
.
ACUTE
NON
11000
LEUKEMIA
LYMPHOBLASTIC
LEUKEMIA
2.10
0-c
WBC
x-x
LYMPHOBLASTS
..-.
LDH
‘10000
00
0
9000
8000
0
E
0
“_‘%
C..)
0
iv
4
6000
-A
0
I
0
0
5000
.-J
0
4000
0
0
0
S
0
S
S
7
#{149}
S.
102
10
NO.OF
2000
S
1O
1O
1000
serum
LDH levels and the blast
leukemia
and nonlymphoblastic
elevation
10 20
of
Serum
vitamin
B,2
in I 2 of the 15
serum
LDH.
No
20
30 10 20
I BUARY
2800
action
30
10 20
intermediate
and
during
a shift in the
the development
LDH
isoenzymes
the
granulocytic
mainly
isoenzymes
is the
and
early
predominant
and
1-3,
MONTHS
of fetal and adult
In hematopoietic
LDH-l-3,
while
in pnoenythroMaturing
lymphocytic
but at the
blast
cells
series
stage,
LDH-5.
In normal
I and 2 predominate,
have as yet not been
with tissue
damage
similar
and
with
respect
both cell types
human
plasma,
of
contain
LDH-I
and -2 are decreased,
resulting
in a predominance
LDH-3.
Mature
peripheral
blood
lymphocytes
mainly
leukemia.
lympho-
of embryonic
pattern
occurs.
isoenzyme
nonmoblasts.303435
granulocytes
are quite
LDH
isoenzyme
content,
30
frac-
hybrid
forms
of
association
of the
of LDH-l
and 5.
is determined
by the activity
of
controlling
LDH-l
and
LDH-5.
isoenzymes
are
found
in various
800
IOCTOBER
Fig. 3.
A 24-yr-old
woman
with acute lymphoblastic
Correlation
of serum LDH level, the number
of circulating
blasts. and the WBC count.
the
blasts
400
20
while
1200
LDH-5
10
genes,
1600
-4
:i:
ISEPTEMSER
of two
Accordingly,
the isoenzyme
content
cells of the same
type is different.
tissues,
enythrocytes
contain
mainly
2000
U
30
leukemia.
lympho-
Lactic
dehydrogenase
occurs
in different
cell
systems
in the form
of five isoenzymes,
LDH-1-5.34
The production
of LDH- I and LDH-5
is controlled
by
tissues,
organs,
2400
E
30
I
DISCUSSION
Their
concentration
the
two
alleles
Different
LDH
3200
30 10 20
I AUGUST
10
I JANUARY
tions
(LDH-2-4)
are considered
LDH-I
and
LDH-5,
formed
by
peptides
making
up the tetnamens
3600
20
30
Fig. 4.
A 1 6-yr-old
woman
with acute lymphoblastic
Correlation
of serum LDH level, the number
of circulating
blasts, and the WBC count.
the
4000
JULY
10 20
cases
showed
megaloblastic
changes
on vitamin
B,2/folic
acid
deficiency.
(Vitamin
B,2 recorded
from
360
pg/ml
to 4000 pg/ml;
folic acid 160-320
ng/ml.)
10
30
I DECEMBER
NOVEMBER
MONTHS
obtained
in two patients.
acid levels
were
available
with
0
BLASTS/mm3
Fig. 2.
Correlation
between
counts
in acute
lymphoblastic
leukemia.
patients
S
S5
S
from data
and folic
3000
S
S
of
and
to their
contain
isoenzymes
but the sources
of this activity
clearly
established.
In conditions
and rapid
cell turnover,
such
as
From www.bloodjournal.org by guest on April 28, 2017. For personal use only.
354
KORNBERG
malignant
neoplasia,
the isoenzyme
damaged
organ
In the
moderately
the
serum
distribution
and cells.
present
study,
serum
elevated
in 6 of
ANLL
and
lymphoma.
LDH
usually
may
rise,
reflects
total
LDH
23 patients
and
that
of the
levels
(26%)
were
with
increased
activity
in isolated
in the serum
of patients
transplantable
lymphatic
Bunkitt’s
lymphoma,
LDH
with ALL
leukemia.
the
serum
contrast
to
the
above
data
lymphoblasts
and
the
findings
as a rough
indicator
more,
when
these
elevated
lymphoma.
LDH
between
acute
those obtained
for other
statistically
groups,
significant.
they
Among
the
were
CML
enzyme
levels
were
elevated
in one
lymphoblastic
crisis and in another
case
tiated
type
prednisone.
are
highly
tic
type.
crisis
In our
who responded
opinion,
marked
suggestive
of acute
Recently,
in the
present
Our results
et al.22 Sactor
the
raised
LDH
levels
towards
obtained
26
who
Angeletti
patterns
and
PU,
of protein
muscle
Bierman
serum
lactic
patients
and
in mice.
2.
BR,
Moore
BW:
in extracts
Res
Hill
by Stuart
have shown
Chromatographic
with
lymphomas
the
and
clinical
status
Cancer
drogenase
of
I961
glutamic-oxaloacetic
4.
BR,
Hill
during
Levi
disease. Cancer
Hill
FL:
Serum
transaminase
masses
JH:
6.
KM.
Cancer
Elevation
lactic
component
in neoplastic
cancer
689,
patients.
J
HI:
Serum
Proc
Soc
lactic
Exp
Biol
7.
Hsieh
KM.
Mao
activity
after
19:700-764,
8.
White
17.
91:626-630,
9.
Suntzeff
lactic
Res
K,
dehydrogenase
Meister
normal
A:
ED,
and
Res
Lactic
J Nail
Huggins
levels
dehydro-
Cancer
Res
Comparative
of serum
transplanted
and
induced
1956
dehydrogenase
Cancer
C:
cancers.
Scoch
F: Glutathione
of tissues
18:682-686,
of pyridine
of experimental
mammary
12. Starkweather
WH,
with
Wroblewski
activities
Cancer
tissues.
1 1 . Rees
glycolysis,
lactic
tumors.
EV:
in mice
16:237-239,
C, Sugiura
tumors.
10.
V, Cowdry
activity
Cancer
Manso
planted
K: Serum
of transplanted
of rodents
Steroid
with
trans-
of certain
10:1263-1271,
influences
nucleotide-linked
Cancer
Res
HK:
Some
tumors
LP:
Serum
cancer
and
on
respiration,
dehydrogenases
20:963-97
observation
1 , I 960
on the
by
of
malignant
found
in
in cell
Biochim
heterogeneity
Ann
NY
Biophys
of lactic
Acad
Weinhouse
Res
I 2:44-49,
dehy-
94:877-889,
Metabolism
citric
acid
of
cycle
in
1952
II.
diseases.
Sci
5:
of the
enzymes.
other
18.
Glycolytic
J NatI
F,
their
enzymes
Cancer
Inst
in
21 :671-
of3O
22.
AR:
system
Lactic
J
Res
IC:
Burkitt’s
from
in
activity
Lactic
in
dehydrogenase
PM,
1964
Berard
CW,
lymphoma:
58:314-321,
1975
and
leukemic
Gral-
A clinicopa-
Alpha-glycerophosphate
cells
and
1961
24:389-399,
Banks
J Med
isoen-
plasma
1955
Hall
Am
and
dehydrogenase
NO,
GP,
of hematopoietic
Stuart
of abnorpatients.
dehydrogenase
tissues
94:912-932,
American
cases.
B, Dick
Lactic
Cancer
Canellos
VT:
of cancer
90:210-213,
Kaplan
JC,
study
Sactor
Med
tissues.
DeVita
drogenase
transport
iS:
RD.
Arseneau
thologic
F, Ladue
neoplastic
HR.
KF:
Sci
Biol
significance
in normal
Acad
Exp
Goldman
20.
Gregory
NY
The
serum
1958
distribution
Ann
III.
in the
21:685-696,
ProcSoc
in human
enzymes.
enzymes
Wroblewski
blood.
nick
Serum
Inst
20:1408-1412,
1950
shift
accompanied
in the levels
tissue.
of enzymes
Cancer
LP:
and
21.
1958
activity
Inst
reductase
MA,
Wroblewski
zymes
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KM.
dehydrogenase
tumors.
Sasamanonth
Spirtes
of glycolytic
Cancer
1959
Hsieh
lactic
55,
excision
a
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different
of the
II. A survey
diseasestates.
genase
reflects
increased
neoplastic
tissues.
tumors.
with
malities
dehydrogenase
Med
In
1958
Natl
1957
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in
in human
CE,
White
16.
in
and
Significance
tissue.
patients
1954
Blumenthal
disease
IS.
measurements
I 956
and
Wenner
transplanted
and
23: 1 1 2- 1 1 7, 1963
dehydrogenase
18:307-313,
in various
dehydrogenase
with
Res
of serum
14:513-515,
Serum
Inst
Hsieh
C:
lactic
correlations
therapy.
Res
NatlCancer
and
14.
Res
ES:
activity
neoplastic
Francis
clear.
1962
Vessell
of
1957
CO.
activity
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62:440-442,
I 3.
leukemias.
LDH
metabolism
encountered
dehydrogenase
Acta
E: Correlation
is not
NCES
1960
L, Emory
LDH
lactate
of rhabdomyosarcoma
20:1229-1234,
Reinhardt
activity
cancer,
of tumor
levels
enzymes
dehydrogenase
with
Brindley
5.
V.
Cancer
HR.
12:660-667,
3.
Suntzeff
leukemias
malignant
distinction
neoplasms
and the markedly
elevated
levels
patients
with ALL may reflect
basic differences
proliferation
and turnover
in these disorders.
REFERE
I.
cellular
anaerobic
serum
series.
are similar
to those
et al.,2’ and other223
with
the
sis in the cytoplasm
of malignant
cells
a high turnover
rate.2237
The variations
have
megakanyonature
were
this
it is of interest
to record
that
other
demonstrated
increased
LDH
levels
in
transplanted
induced
munine
myeloid
leukemias.2729
Increased
of lymphoblas-
chronic
of
levels in 47 of
and in all 36
also recorded
in 86% of patients
from their study,
and
this
respect,
authors
have
primary
and
to vincnistine
and
elevations
of LDH
been recorded
in rare patients
with acute
blastic
leukemia,36
but no cases
of this
studied
to be
patient
with
of undiffenen-
leukemia
markedly
found
patients,
with
with
are
and LDH
levels
tumor
mass.2#{176}In
study,
Bierman
et al.2 reported
elevated
54 patients
with
lymphatic
leukemia
patients
with
myeloid
leukemia.
They
levels
However,
and
in animals
In patients
LDH
levels
900 lU/liter.
In ALL,
LDH
levels
were
markedly
elevated.
In 15 of 19 patients
(79%),
the levels
were
above
900 lU/liter,
and in some cases,
could
be used
of the total tumor
mass.
Furtherlevels
in ALL
were
compared
to
POLLIACK
and
frequently
elevated
above 700 IU/ml,
were found to correlate
well with the
in 6 of 38 patients
(16%)
with malignant
None
of these
patients
had levels
above
AND
mice.
lactic
dehy-
Cancer
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hydrogen
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CG:
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lactic
dehydrogenase
levels
in
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1974,
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59:308-314,
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lactic
site
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Harven
E,
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1975
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bead
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Gralnick
Flor
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124:173-174,
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5,
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From www.bloodjournal.org by guest on April 28, 2017. For personal use only.
1980 56: 351-355
Serum lactic dehydrogenase (LDH) levels in acute leukemia: marked
elevations in lymphoblastic leukemia
A Kornberg and A Polliack
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