From www.bloodjournal.org by guest on June 14, 2017. For personal use only.
Factors
By
Predicting
Histiocytic,
Richard
I.
Fisher,
Long-Term
Survival
or Undifferentiated
Susan
M.
Hubbard,
Jeffrey
Clinical
and
histopathologic
diffuse
mixed,
diffuse
tiated
non-Burkitt’s
determine
Median
70
mo.
male
the
Factors
associated
with
constitutional
involvement,
hemoglobin
huge
of four
marrow
g/dl.
of a given
variables,
status,
mo
a poor
(>10
or
which
and the
LDH
survival
43%
includes
presence
alive
at
U.
The
defined
the
the prototype
since it is the
I 960s,
I 0%-20%
of these
aggressive
most common
type.
of all patients
cytic lymphoma
were
did lead to 30%-50%
with
diffuse
During
diffuse
disagreement
therapy
clinical
enable
histiocytic
survival
with
diffuse
first
report
survival
chemotherapy
numerous
that demonstrated
could be obtained
was published
in l975.
other
authors
have demon-
of patients
with advanced
stages
lymphoma
can achieve
long-term
after
combination
chemothera-
py.’#{176}In
analyzed
1977,
we
56
stage
diffuse
histiocytic
lymphoma
prognostic
factors
predicted
the
combination
strated
that
chemotherapy.”
the determination
involvement
and
initial
evaluation
patient’s
This
patients
extent
allow
Blood,
of
study
sites
tumor
mass
to accurately
between
Vol. 58,
No.
these
lymphoma
is considerable
three
1 (July). 1981
diagnoses
the
trial
compared.
In
patients
for
conversely
yields
those
excellent
pathologists
are
have
National
Cancer
important
survival.
long-
is not uncom-
treated
identically.
also suggested
that
permit
obtained
patients
in order
to
treatment
with
with
AND
diffuse
between
I 964
and
the
various
and
medical
records
were
were
(R.I.F.
and
by the two
histiocytic,
at
the
evaluated
completely
interpretation
initial
pathologic
biopsy
site
that
diffuse
lymphoma.
and
All
reached.
material
one
Any
biopsy
into
Institute
this
study.
interpreted
(C.W.B.
The
by two of
pathologic
pathologists
contained
the
undifferentiated
Cancer
for entry
S.M.H.).
a consensus
study,
the
and
National
reviewed
experienced
of
METHODS
mixed,
treated
I 977
to
determine
programs
for
diffuse
lymphoma
more
accurate
comparisons
in different
clinical
trials.
lymphoma
authors
Institute
prognostic
factors
influencThis
information
should
also
investigators
of current
of patients
reviewed
material
was
and
and
iC.)
In order
to be included
in this
had to include
at least
one
of the
previously
containing
areas
mentioned
forms
of nodular
lympho-
of
the
a
From
metric
about
mixed
(neither
of these
histopathologic
and,
the
non-Burkitt’s
the
demonof tumor
during
predict
expert
subgroups
authors
clinical
All
to determine
what
success
or failure
of
That
of the
of
clinical
of
and
therapy
MATERIALS
advanced
prognosis.
study,
however,
provided
no information
with a Rappaport
diagnosis
of diffuse
or diffuse
undifferentiated
groups
is rare).
There
overlap
of
one
cases
at
determine
the
ing long-term
should
results
that
with
strated
that a subset
of diffuse
histiocytic
disease-free
survival
among
adequacy
subgroups
lymphoma
rarely
achieved
long-term
either
radiation
therapy
or single
agent
chemotherapy.
The
long-term
disease-free
combination
Subsequently,
of
be
the
subclassification
of these
aggressive
forms
of diffuse
lymphoma
on histopathologic
criteria
may
provide
significant
prognostic
information.
2.13
and
stages
can
subsets
is inadequate
current
mon.
Often
the
Recently,
several
treated
free at 5 yr.3’4
with
more
advanced
whom
in
with
survival.
stage
I patients
were
treated.2
With
the advent
of
pathologic
staging
and
improved
radiotherapeutic
techniques,
70%-80%
of stage
I patients
are now alive
disease
Patients
therapy
for
define
did
differences
in any
results
may
Strauchen
Knowledge
factors
the
Therefore,
we have reviewed
the clinical
history
and
pathologic
material
from
151 patients
with all stages
of mixed,
histiocytic,
and undifferentiated
lymphomas
histio-
alive at 5 yr.’ Radiation
survival
at 5 yr when
data
to
correlate
factors.
therapeutic
such
or
categories
prognostic
In
according
significant
clinical
of these
before
with
these
described
involvement.
patients
of Rappaport
groups
did
current
term
THE
LAST
I 5 yr, the results
obtained
from the treatment
of the aggressive
forms
of
diffuse
lymphomas
have
improved
significantly.
Diffuse
histiocytic
lymphoma
has classically
been
selected
as
lymphomas
nor
patients
URING
Wesley,
gastrointestinal
of these
patient
survival,
whom
bone
a huge
Robert
categories
define
is needed
best
Berard,
with
histopathologic
addition,
by a set
sex,
symptoms,
or absence
of
mass
distribution
masses
W.
classification
previously
bone
involvement,
>250
Costan
Mixed,
C. Young
abdominal
not
include:
abdominal
was
to
stage.
hepatic
serum
patient’s
with
DeVita,
Robert
contrast,
survival.
prognosis
cm)
of
reviewed
advanced
involvement,
<12
prediction
34
symptoms.
gastrointestinal
cases
long-term
T.
and
undifferen-
been
predict
was
1 51
diffuse
have
that
of all patients
marrow
with
from
and
lymphomas
factors
survival
sex,
D
material
histiocytic.
Vincent
Cossman,
in Diffuse
Lymphoma
indeed,
tutes
the
Medicine
Research
ofHealth,
Submitted
Address
Room
((
Bethesda,
November
reprint
12N226,
1981
Branch.
Branch,
requests
National
by Grune
Laboratort’
National
of Pathology.
Cancer
Institute,
accepted
March
and
National
BioInsti-
Md.
25, 1980;
to Richard
Cancer
& Stratton,
Institute.
I. Fisher,
4. /98!.
M.D.,
Bethesda,
Building
Md.
/0,
20205.
Inc.
0006-497l/8l/580!-0007$Ol.00/0
45
From www.bloodjournal.org by guest on June 14, 2017. For personal use only.
46
FISHER
ma, in addition
to
lymphoma
therefore,
and,
hundred
and
The
are
fifty-one
clinical
shown
The
age
all patients
night
sweats,
45%.
The
not
of
were
10%
were
weight)
diffuse
organ
considered
50%
present
in
60%;
by
the
I, 23%
were
evaluation
then
that
organ
Ann
Arbor
II,
14%
was
Conferstage
was
was
initial
to the
patients
given
to 29 of the
more
treatment
received
1 . Clinical
37 radiation
extensive
fields.
alone
and
Histologic
Characteri
With
Diffuse
Lymphomas
Characteristic
predni-
present
other
patients
plus
at restagthere
a complete
at restaging
were
IV
(7%)
agents.
in whom
attaining
ized
calculated
method.
Wilcoxon
from
test
test.2’
the relative
proportional
was
clinical
were
classified
the
were
All p values
regression
method
are
best
backward
was
for predicting
be individually
considas nonre-
pair,
then
generalized
and
gave
to find
the same
final
To
most
assess
are
used
also
found
analyzed
to continue.
used
of prognostic
important
factors
two
was
was
subset
the
prognostic
of size
method
by the
type.
factors
on survival,
the
used.
A modified
forward
procedure
regression
by
Kruskal-Wallis
statistically
two-sided
Of the
all subsets
plotted
by the general-
compared
applied
a stepwise
and
analyzed
of the
survival.
important,
stepwise
results
or
rates
of therapy
were
effect
of different
prognostic
hazards
model
of Cox22 was
set of factors
the
start
curves
of Gehan’9
test of Breslow.2#{176}Response
exact
the
Survival
to
check
The median
now
exceeds
follow-up
6 yr.
The
(20%)
noted
in
achieving
1 1 /54
of Patients
Percent
100
93
62
58
38
Age (yr)
Less than 20
13
9
20-40
40
26
40-60
70
46
28
19
disease-free
achieved
survival
on the study
for all 151
survival
and
Females
survival
is 34 mo
than
70 mo. As
previous
studies,”23
only
a complete
remission
those
patients
had
prolonged
survival.
Fifty-four
percent
a complete
remission,
and
has
not
been
reached,
with
of all patients
their
median
76%
of the
complete
responders
alive
at 70 mo. The
median
survival
of the 37% of patients
who achieved
a partial
response
and the 9% who had no response
are 6 and 7
mo, respectively.
Complete
response
rates according
to
.0
3.9
symptoms
A
83
55
B
68
45
0.S
TOTAL
DEilO
151
80
[7
diagnosist
Diffuse
mixed
3 1
20
Diffuse
histiocytic
9 1
60
Diffuse
undifferentiated
19
13
10
7
non-Burkitt’s
Unclassifiable
:-
Q.5
0.5
Stage
-
-
I
20
13
II
34
23
Ill
21
14
IV
76
50
37
25
93
61
16
11
5
3
-
0.2
therapy
Radiation
Combination
chemotherapy
0.1
0 .0
Combined
modality
Other
Fever,
tAccording
night
sweats,
or loss of 10%
to Rappaport
classification.
of total
body
A
the
factors.
for all patients
actuarial
patients
is shown
in Fig. 1 . Median
with
43% of patients
alive
greater
Males
Histologic
to
RESULTS
bleoI or II
Sex
Initial
those
or
radiation
tumor
Those
vincristine,
with stage
Number
Greaterthan6O
III
7
single
of residual
disease
All
Of these
and
15 1
Constitutional
or
patients,
(61%).
sties
Total Patients
was
life table
find
or mechlorethamine,
(C-MOPP
or MOPP);5
doxorubicin,
For patients
radiation
field
and
received
received
responders.
microscopic
responders.
5 (5%)
2 (2%)
no evidence
size
stage
Combination
vincristine,
cyclophosphamide
and prednisone
Institute
Involved
for 93 patients
and 40 received
cyclophosphamide,
mycin,
and prednisone
(BACOP).7
(56%)
Cancer
(25%).
cyclophosphamide,
sone (CVP);’8
37 received
vincristine,
procarbazine,
30/54
National
with
complete
with
chemotherapy,
AL.
sponders.
stepwise
III,
patients
therapy,
called
with
97
and
in tumor
partial
the
combination
radiation
decrease
Fisher
staging
adequate
stage
in 37
received
14 received
Table
Ifan
performed,
referral
radiation
chemotherapy
disease,
for pathologic
outlined
stage
alone
remainder
93 patients,
criteria
as
data
For
received
patients
been
Survival
of admission,
all staging
et al.’6
been
time
those
remission
ered
unclassifiable
analysis,
(86%)
chemotherapy,
have
to
following
field
the
ing
a 50%
IV.
of radiation
extended
not
were
at the
this
current
As
of patients
therapy
consisted
had
evaluable.
stage
Initial
For
by Chabner
site
not
13%
extensive
Only
Rappaport
histiocytic,
and
received
male.
(fever,
were
to the
C-MOPP.
83
combination
9% of
symptoms
1 3%;
performed
to our
defined
been
of a given
while
patients
8 to 74 yr. Only
according
20%;
1 5 1 patients
plus
disease,
the
according
have
and
of the
body
mixed,
One-
7%.
reinterpreted
ence,’7
of these
non-Burkitt’s,
radiation
a nodular
analysis.
Constitutional
of total
diffuse
Staging procedures
were
defined in prior reports.5’7”5
that
this
criteria.
from
diagnoses
undifferentiated
lymphoma,
above
a range
20 yr old.
pathologic
classification’4
the
percent
49 yr with
or loss
initial
considered
in
characteristics
I . Sixty-two
less than
was
included
met
histologic
was
were
lymphoma,
patients
and
in Table
median
diffuse
diffuse
ET
weight.
-
-j-----0
0
-_-
---i
36
54
70
MON
Fig. 1 .
Actuarial
survival
forms of diffuse lymphoma.
t_
90
108
I
126
144
I
162
.
180
I HO
curve
for all patients
with
aggressive
From www.bloodjournal.org by guest on June 14, 2017. For personal use only.
PROGNOSTIC
stage
FACTORS
were
as
FOR
DIFFUSE
follows:
stage
III, 66%;
Eight clinical
LYMPHOMAS
stage
I, 100%;
47
stage
and stage
IV, 38%,
factors,
easily determined
56%;
II,
‘0i0.
prior
C .0
initiation
of therapy,
can be utilized
to predict
the
survival
of patients
with these diffuse
lymphomas.
The
relationship
of the patients’
sex to his survival
is shown
in Fig. 2. Survival
of female
patients
exceeded
that of
male patients
(p = 0.05).
Of interest,
sex is the only
clinical
survival
factor
without
there
with
tumor
The
greater
any
was
no significant
particular
stage
involvement,
or histology.
presence
of fever,
night
than
10% of the total
association
of disease,
sweats,
or weight
body weight
was
3.4
3.3
-
0.2
-
of
median
survival
toms
is 10 mo,
patients
has
for patients
while
the
not
been
compared
0.002).
and
with
a
(p
= 0.002)
to 67%
Likewise,
Fig. 3.
(data
the
The
not
fact that
complete
patients
partially
explained
huge abdominal
tract
in the
poor prognosis
Although
bone
was inversely
correlated
rate and also survival,
as
The only exception
is the
patients
with stage
II disease
response
rate
and
survival
with
stage
III
lymphoma.
by the inclusion
masses
involving
had a lower
than
those
This
fact
is
of 5 patients
with
the gastrointestinal
stage
II category.
These
patients
and will be discussed
later.
only
I 5% of all evaluable
patients
marrow
infiltration
with
malignant
3;H3L.
3EP3
MPLE
58
24
had
had
lymphoma,
18
6
‘?
54
Survival
prognosis
complete
X
:::
P<0.002
SOOE
SC
108
26
[44
162
HO
of all patients
of these
response
according
patients
rate was
to their
was
only
stage.
extremely
9% for
poor.
patients
bone
marrow
infiltration
versus
62% for all other
without
marrow
lymphoma
(p < 0.002).
As
in Fig. 4, median
survival
drops
from 5 1 mo for
with
shown).
A patient’s
initial
stage
with the complete
response
shown
in Fig. 3 (p < 0.002).
48
II
MO9THO
with constitutional
sympmedian
for asymptomatic
reached
58GE
#{163} STHOE
i
o.o
constitutional
symptoms
was 38%
for asymptomatic
patients
(p <
[7
9
..O-.---
loss
asso-
ciated
with both a lower
complete
response
rate
survival.
The complete
response
rate for patients
507E
[6
21
0.5-
of
site
[7
3’
.
-,--‘--.
3.5
H
that
significantly
affected
patient
affecting
the complete
remission
rate.
Furthermore,
females
DEHO
20
to the
patients
shown
all other patients
without
marrow
involvement
to 6 mo
for patients
with
it (p < 0.002).
This
detrimental
effect of bone marrow
involvement
was also
the subset
of patients
with diffuse
histiocytic
ma.
No
other
histologic
category
had
numbers
analyzed
a
of patients
independently.
The
and
For
prognosis
gastrointestinal
this analysis
inal
mass
with
marrow
of patients
with
involvement
we have again
as one
greater
present
in
lymphosufficient
involvement
huge
to be
abdominal
mass
is shown
in Fig. 5.
defined
a huge abdom-
than
10 cm
in diameter,”
.3
0.5
3.9
T34L
0.8
3.8
[7
3
L3
i:
..O’
3
55P,[4’i35TVi
S
-555j,
P
EEMHLE
L
[).5
<0 002
[[50V4
. .=.
::: t1
3-
3.4
3.3
o.oF
0.?
-
0.
0 .
0.1
--
0
0
0
35
I
54
1(19
126
44
.
0.0
-.
90
52
80
0
18
35
0
54
MONT
Fig. 2.
Survival
of all patients
according
to their
sex.
Fig. 4.
Effect
of bone
.
72
I
90
08
125
[44
1
162
IS
marrow
involvement
on survival.
i
80
From www.bloodjournal.org by guest on June 14, 2017. For personal use only.
48
FISHER
ET AL.
1.0
response
hemoglobin
0.9
0
NEGATIVE)
14
0
POSITIVE1
15
0.7
>
OERO
tO
therapy
was less
and
survival.
than
12 g/dl had
Patients
a 41%
whose
complete
response
rate and 10 mo median
survival
compared
63% and 7 1 mo for patients
whose
hemoglobin
0.8
TOTAL
136
to
greater
than or equal
Finally,
patients’
P.30.002
to 1 2 g/dl
(p <0.002).
initial
serum
LDH
(lactic
to
was
dehy-
0.6
drogenase)
values
provided
useful
prognostic
information. Patients
with an LDH
greater
than 250 U had a
39% complete
response
rate and a median
survival
of
0.5
0.4
1 3 mo. In contrast,
patients
less than 250 U, had a 74%
0.3
a median
survival
that
with a normal
LDH,
complete
response
rate
was
not
reached
with
i.e.,
and
57%
of
patients
alive at 70 mo (p = 0.003).
The patients
could
also be analyzed
to determine
whether
these seven clinical
factors
were as important
in patients
with
localized
disease
(stage
I or II)
or
0.2
the
0.1
0.0
0
18
36
54
72
90
108
126
144
162
lAO
MONTHS
Fig. 5.
involvement
Effect
of huge
on survival.
Although
only
had
a huge
involvement,
10%
= 0.002).
gastrointestinal
to adversely
mass
of all evaluable
with
gastrointestinal
patients
abdominal
mass
with
their
complete
response
median
survival
that of all other
p
abdominal
advanced
disease
were made
among
actually
gastrointestinal
rate of 7%
of 6 mo were significantly
patients
(60% and 5 1 mo,
and
less than
respectively,
We
have
previously
reported
that
both
involvement
and huge
masses
appear
affect the survival
of patients
treated
with
combination
chemotherapy.”
In the
present
study
with a larger
number
of patients,
we found
that only a
huge
abdominal
mass
with
gastrointestinal
involvement
adversely
affects
prognosis.
We cannot
demonstrate
that
abdominal
important
gastrointestinal
involvement
without
a huge
mass
or huge
masses
in other
sites
are
prognostic
factors.
The poor
prognosis
of
these patients
with huge abdominal
intestinal
involvement
could
also
masses
and gastrobe demonstrated
in
the subset
of patients
with diffuse
histiocytic
lymphoma. There
were insufficient
numbers
of these patients
in other
histologic
categories
to analyze
them independently.
Involvement
of the liver by these
forms
of diffuse
lymphoma
also adversely
affects
the prognosis.
Twelve
percent
of evaluable
patients
had documented
parenchymal
involvement.
Of these patients,
a complete
response,
and median
survival
hepatic
25% had
was 6 mo.
This
is significantly
worse
than
the results
from
all
other
patients
without
liver invovement,
i.e., 59% and
51 mo, respectively
(p = 0.01).
In this analysis,
we were unable
to demonstrate
that
other
common
sites of extranodal
involvement
with
diffuse
spleen,
cantly
The
lymphomas,
such
or central
nervous
lower survival.
patient’s
initial
as
the
system,
hemoglobin
skin,
resulted
level
lung,
bone,
in a signifipredicted
(stage
stage
III or IV). When
comparisons
III and IV patients
only, sex,
symptoms,
masses
with
hemoglobin
marrow
involvement,
huge
abdominal
gastrointestinal
involvement,
LDH,
and
all significantly
affected
survival.
Liver
involvement
although
was also
difference
icance
(p
involvement
this
=
0.10).
caused
associated
with
did not reach
a lower
statistical
survival,
signif-
Obviously,
bone
marrow
or
the patients
to be classified
liver
as
stage
IV and thus were
not found
in stages
I or II
patients.
Of the remaining
factors,
only symptoms
and
huge abdominal
masses
with gastrointestinal
involvement were predictive
of lower survival
for stage
I or II
patients.
Sex and level of LDH or Hgb did not statistically predict
survival
for stage
I or II patients.
In addition
previously,
we
histopathologic
lymphomas
information.
Rappaport
to
have
subclassification
provides
additional
Survival
classification,
the prognosis
worsens
histiocytic
to diffuse
there
is no significant
(p = 0.27).
In
1978,
the
clinical
factors
attempted
to determine
discussed
whether
of these
diffuse
useful
prognostic
of all patients,
according
to the
is shown
in Fig. 6. Although
from
diffuse
mixed
to diffuse
undifferentiated
lymphoma,
difference
among
the categories
Strauchen
et
al.
proposed
a new
pathologic
system
of classifying
patients
types
of diffuse
lymphoma.’2
The authors
histo-
with
these
retrospec-
tively
reviewed
a series
of 66 cases
and divided
the
patients
into the five categories:
large
cleaved,
large
noncleaved,
mixed
follicular
center
cell, blastic,
and
pleomorphic
pyroninophilic.
In the initial
report,
this
classification
appeared
to delineate
good,
intermediate,
and
poor
prognostic
groups.
The
pathologic
material
from this initial
report
has been re-reviewed
by one of the original
authors
(C.W.B.).
of the cases were the original
interpretations
ible. This classification
was then applied
series
of
I 5 I cases.
The
results
are
In only 67%
reproducto the larger
demonstrated
in
From www.bloodjournal.org by guest on June 14, 2017. For personal use only.
PROGNOSTIC
FACTORS
FOR DIFFUSE
LYMPHOMAS
49
include:
)
(1
advanced
huge
ment;
0_H
abdominal
(6) liver
12 g/dl;
These
affected
and
0.4
0 .
TOTALAT
SEAT
48
34
14
[7
OML
12
8
GUI5
.
0.1
‘
0.9
‘
0
18
,-
‘
36
9
54
I
I
77
90
-
[7
Fig. 6.
according
l
I
108
126
Survival
of the aggressive
forms
to the classification
of Rappaport.
7. Although
the
as described
in the
ries do not separate
different
prognostic
none
of Strauchen’s
curves
PO27
I
(8)
serum
16,
lAO
performed
appear
of diffuse
in the
lymphomas
same
clinical
prognostic
Cox
regression
to delineate
the
relative
was
strength
of any
of
these eight clinical
prognostic
factors
while taking
into
account
the contribution
of all the other
factors
listed
above.
Because
each
highly
of the eight
predictive
variables
of survival,
it was
was
individ-
not
possible
to unequivocally
define
of each of these factors.
equal
weight
to a factor
poor survival
but present
the exact
order
of importance
Moreover,
the model
may give
that is strongly
predictive
for
in relatively
few patients
and
a factor
that is associated
in survival
but is present
with a moderate
decrement
in a larger
proportion
of the
population.
patient’s
However,
course
was
the
best
prediction
achieved
using
a set
remissions
were
the
factors
predict
than
250
U.
achieved.
Indeed,
there
was
the survival
of patients
with
poor
who achieved
a complete
remission
of other
complete
responders.
This
the concept
that
improved
diffuse
lymphoma
will result
of complete
remissions
are
the
of diffuse
histiocytic
lymphoma.13
They
reported
an
86% concurrence
rate between
two pathologists
reading the
not determine
the
reproducibility
of a given
pathologists’
reading.
survival
of patients
with four of the subcategories
slides
The
was
identical
but
noncleaved
Si
to
Whether
provide
to or greater
factors
the
can
but
inferior
cells.
fications
rable
independently
remains
did
the
group
other
prognostic
than
with
large
histopathologic
clas-
information
that
provided
compa-
by the
clinical
to be determined.
Although
we initially
prognostic
factors
TOTAL
had hoped
in sequential
that
we could place
order
of impor-
0080
I RRGI
CI EHVEO
23
TO
TI
33
7
03
1 ARGO .P4ONCI
I HAT
3T
4
A
8,010
CUIHK
TA
2
x
84 TST It
35
24
0
PLTOMORPHIC
FOIl
CINIII9
CUt
I’TKO$INOPHII
POTS
IC
Ii .6
1
that
greater
the exception
of sex, all
patients
because
fewer
Strauchen
system
were not satisfactorily
reproducible.
Armitage
et al. used a similar
classification
scheme
and applied
it to patients
with a Rappaport
diagnosis
CONCLUSIONS
studied
(5)
involveless than
to these clinical
factors,
histopathologic
of these
patients
according
to
of the
of four
prognostic
variables
that defined
the patient’s
status
in
regard
to bone marrow,
huge abdominal
masses
with
gastrointestinal
involvement,
symptoms,
and sex.
have
with
of
(3)
involvement;
systems
proposed
by Rappaport’4
or Strauchen’2
did
not add significant
additional
prognostic
information.
In fact,
the
interpretations
established
by the
order
factors.
analysis
symptoms;
marrow
LDH
factors,
survival
obtained.
In contrast
subclassification
I
144
initial
report,
Strauchen’s
categothese
patients
into significantly
groups
(p = 0.16).
In addition,
categories
correlated
with
the
previously
described
A multifactor
We
bone
once
agains
emphasizes
survival
of patients
with
when
larger
numbers
OHL1
MONTHS
ually
(2) constitutional
(4)
no evidence
that
prognostic
factors
was less than that
(4.3
Fig.
sex;
masses
with gastrointestinal
involvement;
(7) hemoglobin
clinical
the
complete
:
male
stage;
..
long-term
0.3
survival
in patients
with diffuse
undifferentiated
non-Burkitt’s
spective
review
for a median
results
have
of 1 5 1 patients
mixed,
lymphoma
who
have
histiocytic,
or
in a retrobeen
followed
time in excess
of 6 yr. Indeed,
improved
been obtained
during
the last I S yr. since
43% of all patients
are alive
factors
that can be determined
therapy
adversely
affected
at 70 mo. Eight
clinical
prior to the initiation
of
the
prognosis.
They
0.?
0.I
0.11
0
I
I
IA
36
I
[4
I
I
I
7?
90
108
*
I
126
I
144
,
62
I
80
MONTHS
Fig. 7.
according
Survival
of the aggressive
forms
to the classification
of Strauchen.
of diffuse
lymphomas
From www.bloodjournal.org by guest on June 14, 2017. For personal use only.
50
FISHER
tance
by use
of a Cox
regression
model,
this
goal
was
not possible.
to the fact
Part of the difficulty
could
be attributed
that the regression
model
may give equal
importance
in very few
to two
patients
second
that
one
types
but
may
of factors-one
has devastating
be
present
that is present
impact,
and a
in about
half
of the
patients
but
has
only
moderate
negative
impact.
Nevertheless,
when
a patient’s
status
was defined
in
regard
to sex, symptoms,
bone marrow
involvement,
and
huge
abdominal
masses
with
gastrointestinal
involvement,
no other clinical
variable
provided
significant additional
prognostic
information.
No truly comparable
analysis
of the factors
predicting
long-term
been
survival
published.
advanced
treated
Stage
marrow
that
dealt
involvement,
it is a huge
abdominal
out a huge abdominal
of
with
mass
non-Hodgkin’s
when
one
those
factors
with
than
to be
gastroin-
with
has
that influenced
advanced
stages
lymphoma
been
limited
clinical
the
were
not
part
of our
investigation
trials
world
are
in an
of
prognostic
currently
in progress
attempt
to
improve
the
therapy
of diffuse
lymphomas.
In order
to compare
these regimens,
it is important
to know the distribution
of clinical
prognostic
factors
present
in a given
trial
and the complete
response
rate for each category
of
This
predict
patients
is especially
important
that
differences
in
entering
of
a given
study
magnitude
as
could
the
since
one
prognosis
the
can
of
be of the
differences
same
observed
between
two therapeutic
modalities.
Finally,
it may
now be appropriate
to attempt
to develop
new treatment strategies
mas-specifically
prospectively
half
with the less intencyclophosphamide,
chemotherapy,
nodular
serum
LDH was a poor prognostic
factor
in all types of
non-Hodgkin’s
lymphomas25
and Arseneau
reported
similar
results
in Burkitts’
lymphoma,26
but otherwise
patients.
easily
mass
with-
(approximately
treated
or absence
of constitutional
symptoms.
certainly
are consistent
with our findings
notes that patients
with prior treatment
and
anlaysis.
In addition,
in the M.D.
Anderson
study,
bone
marrow
biopsy
and
liver
biopsy
were
not
routinely
performed,
and serum
LDH
levels were not
analyzed.
Ferraris
et al. have reported
that an elevated
order
lymphoma
diffuse)
presence
These results
throughout
mass.
et al. studied
the
survival
in patients
nodular
and half
sive combi nation
with
and
factors.
Numerous
gastroin-
not a huge
involvement
vincristine,
and prednisone.24
Factors
that
influenced
prognosis
included
tumor
bulkiness,
prior
therapy,
nodular
or diffuse
pattern
of growth,
hemoglobin
level,
there
These
factors
are also imporalthough
we can now demon-
testinal
involvement
that is important,
in another
site or a gastrointestinal
Cabanillas
response
and
has
only
and a tumor
mass greater
in a single location
were found
prognostic
factors.
in the current
study,
strate
lymphomas
analysis
diffuse
histiocytic
lymphoma
combination
chemotherapy.”
bone
testinal
involvement,
10 cm in diameter
diffuse
previous
stages
of
with
intensive
IV disease,
poor
tant
in these
Our
ET AL.
for some patients
with diffuse
those
patients
in whom
predict
poor therapeutic
results.
lymphowe can
REFERENCES
1. Zuks
Kim
Z,
H:
Peckham
lymphomas.
3.
with
4.
Semin
HM,
Kinzie
Miller
localized
histiocytic
Toonkel
LM,
chemotherapy.
7.
Berd
D, Cornog
Young
8.
Skarin
chemotherapy
of
Rosenthal
of advanced
of patients
R,
BA,
RG,
Levitt
Schein
M,
35:1050-1054,
SP,
P,
Hubbard
JR:
with
JC,
Berard
sification
chemotherapy
in
lymphomas.
Maloney
WC,
Frei
lymphoma
Ann
E: Combination
with
bleomy-
Haut
Moon
A,
TE,
Stephens
Fisher
of adriamycin
R,
containing
of diffuse
RL,
Haskins
combina-
lymphoma.
Cancer
HM,
Bitran
Ultmann
JD,
vincristine,
Miller
JB,
Stein
Daly
K,
Roth
RA,
methotrexate
(COMLA)
advanced
JE,
Streuli
with
combination
diffuse
histiocytic
RS,
NO:
leucovorin
sequential
lymphoma.
chemoAnn
Intern
1980
DeVita,
for
VT, Johnson
BL,
advanced
diffuse
with
combination
Simon
R,
histiocytic
Young
RC:
lymphoma
chemotherapy.
Am
J
Med
1977
CW:
JA,
Young
Clinical
of diffuse
RC,
DeVita
relevance
histiocytic
VT,
of the
Anderson
T,
histopathological
lymphoma.
Fantone
subclas-
N EngI
J Med
Corder
MP,
299:1382-
1387, 1978
I 3.
Armitage
Clinical
non-Hodgkin’s
U,
treatment
Berard
EN,
GE,
treatment
Golomb
cytarabine
92:785-790,
63:177-182,
cyclophosphamide,
histiocytic
DL,
for
following
Long
1976
DS,
and
combi-
Metz
Byrne
Superiority
Mintz
I 2. Strauchen
BA,
PN,
JJ,
in the
1 1 . Fisher
RI,
Prognostic
factors
a poten-
prednisone
1979
EP,
Med
and
1977
Grozea
Butler
CA:
Sweet
Lester
1975
Chabner
combination
diffuse
chemotherapy
rescue,
adjunctive
Bertino
treated
adriamycin,
(BACOP)
Coltman
tion
vincristine,
49:759-769,
Cyclophosphamide,
non-Hodgkin’s
lymphoma,
lymphoma
Hubbard
CL,
10.
Martin
and
SE,
FS,
43:417-425,
1975
Cancer
VT,
II
Jones
Morrison
ML,
cyclophosphamide,
Blood
therapy
histiocytic
histiocytic
advanced
85:417-422,
AT,
adriamycin,
1977
ii,
I and
1 :248-250,
Bleomycin,
prednisone
treatment
Med
DeVita
RC:
and
Intern
diffuse
chemotherapy.
PS,
Butler
Chabner
J, DeConti
in diffuse
Schein
vincristine
cm,
(BACOP).
1980
GP,
Lancet
Survival
radiotherapy
45:249-260,
Advanced
sequential
of
Grien
39:342-348,
iF,
staged
results
disease.
remission
cw,
the
RC:
curable
nation
SA,
Cancer
non-Hodgkin’s
D,
JE:
Cancer
Gamble
Laparotomy
the
Variakajis
N, Ultmann
LM,
Canellos
of
DL,
lymphoma.
Fuller
VT,
Young
6.
Rosenberg
1974
1:41-58,
Sweet
Oetzel
Cancer
DeVita
I
J,
JB,
CC:
term
HS,
correlations.
therapy
Hematol
JD,
Preliminary
tially
Dorfman
9.
lymphomas:
SP,
ME,
Clinicopathologic
Radiation
Shullenberger
5.
Kadin
IV.
Mi:
Bitran
Golomb
M,
1973
31:806-823,
2.
Bull
Lymphoma.
tion
934,
usefulness
of advanced
1979
JO,
Dick
and
diffuse
FR,
Platz
reproducibility
histiocytic
CE,
of
lymphoma.
histologic
Am
Lennert
subclassifica-
J Med
67:929-
JT:
From www.bloodjournal.org by guest on June 14, 2017. For personal use only.
PROGNOSTIC
I 4.
Rappaport
of Tumor
Forces
I 5.
FOR DIFFUSE
FACTORS
H: Tumors
Pathology,
Institute
of the
Section
chemotherapy
5,
with
in lymphosarcoma
system,
8. Washington
in: Atlas
DC,
Armed
1966
DeVita
nitrogen
and
51
hematopoietic
3, Fascicle
of Pathology,
Lowenbraun
LYMPHOMAS
K samples
21.
VT,
Serpick
mustard,
AA:
Combination
procarbazine,
reticulum
cell
sarcoma.
and
prednisone
25:1018-
to unequeal
P: Statistical
Wiley,
22.
patterns
of censorship.
Biometrika
1970
Armitage
York,
Cancer
subject
57:579-594,
Methods
in Medical
Research.
New
I 971
Cox
D:
34:187-200,
Regression
models
and
life-tables.
J R Stat
Soc
B
1972
1025, 1970
16.
Hubbard
staging
Chabner
BA,
PP.
M: Report
Kaplan
Bagley
Advanced
therapy
Intern
I 9.
trarily
20.
CM,
Med
Gehan
RC,
Canellos
Sequential
Intern
Med
76:227-234,
Musshoff
K,
GP,
23.
BA,
for
non-surgical
85:149-154,
Smithers
on Hodgkin’s
VT,
Intensive
cyclophosphamide,
Disease
DW,
Staging
Anderson
T,
Berard
CW,
non-Hodgkin’s
CW,
cyclical
Canellos
combination
vincristine,
samples.
N: A generalized
24.
and
GP:
chemo-
prednisone.
Ann
advanced
Wilcoxon
Kruskal-Wallis
test
for
comparing
52:203-223,
test
arbi-
1965
for comparing
26.
nick
Burke
pathologic
Smith
predicting
AM,
Guintini
a prognostic
DeVita
VT,
Chabner
for
TL,
Moon
response
and
lymphoma.
TE,
Butler
survival
Arch
JJ,
in adults
Intern
Mcd
tool
P. Gaetani
for
GF:
Serum
non-Hodgkin’s
lactic
dehydro-
lymphomas.
Blood
1979
Arseneau
HP,
RI,
1977
JS,
non-Hodgkin’s
Ferraris
as
Fisher
1978
54:928-932,
Biometrika
F,
V: Factors
genase
RA,
Rep6l:l057-1066,
138:413-418,
25.
Bender
Norton
L, Young
RC: Combination
chemotherapy
lymphoma:
Results
of long-term
follow-up.
Cabanillas,
Rodriquez
with
1971
Berard
1972
E: A generalized
singly-censored
Breslow
Young
VT:
Ann
Res 31:1860-1861,
DeVita
lymphosarcoma:
with
HS,
of the Committee
Classification. Cancer
18.
RE,
SK,
DeVita
lymphoma.
CancerTreat
I 976
I 7. Carbone
Tubiana
Johnson
SP, Johnson
of non-Hodgkin’s
DeVita
study
JC,
VT:
Canellos
GP,
American
of 30 cases.
Am
Banks
PM,
Burkitt’s
J Med
Berard
lymphoma:
3 1 4-32
1 , I 975
CW,
A
Gralclinico-
From www.bloodjournal.org by guest on June 14, 2017. For personal use only.
1981 58: 45-51
Factors predicting long-term survival in diffuse mixed, histiocytic, or
undifferentiated lymphoma
RI Fisher, SM Hubbard, VT DeVita, CW Berard, R Wesley, J Cossman and RC Young
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