From www.bloodjournal.org by guest on January 27, 2015. For personal use only.

A Multivariate

Analysis

in Chronic
By
The

prognostic

findings
was

at
analyzed

patients.
the

value

From

whole

the

of

in a
the

it

was

following

The

poor

cytogenetically

and

multivariate
that

could

analysis
From

regression

was
the

emerged:

NALYSIS
OF PROGNOSTIC
permitted
the design ofstaging
hematologie
disorders,
thus
playing

studied

the

contribution

of

regression

of

was

as

restricted

a
to

survival
group

splenomegaly.

the disease.2
Because
of this, interest
in the last years
has been focused
on the study of prognostic
factors
in
It is well

known

that

patients
without
the Philadelphia
show a poorer
prognosis,
with a
the blastic
statement
CML

the minority
more

should

be regarded

as a distinct

patients

study
mixture

at the

and

be

Thus,
a major
criticism
of
factors
in CML
is the lack

considered
separately.7
most reports
on prognostic
of karyotypic
well as the

entity

in a high percentage
of patients,
of Ph-positive
and Ph-negative

time

of prognostic

as

evaluation.69#{176}24

proposed
a staging
system at diagnosis
of CML
based
on a few simple
clinical
and hematologic
features.
However,
a multivariate
survival
analysis
in a large

entI,

Postgraduate

Hospital

School

Clinico

of

Hematology

Provincial.

Farreras

University

of

Va!-

Barcelona.

Spain.
Submitted
Address
graduate

March
reprint
School

Clmnico
y Provincial.
(C)
/ 982 by Grune

3. /982;
requests
of

July

Francisco

Hematology
Casanova,
& Stratton,

0006-4971/82/6006-00I0$01.00/0

1298

accepted
to

/2.

Farreras
/43,
Inc.

1982.

Cervantes.
Barcelona

M.D..

ValentI,
(36),

PostHospital

Spain.

three

with

risk.

stage
or

Ill (high

four

factors.

at different

chromosomal

significance

stages

study

work

to derive

attempted

a staging

of such
an analysis,
correlation
of Tura
present
series.

Patients

and
183

available

features

pres-

of blastic
CML

AND

Diagnostic

Criteria

consecutive

patients

over a period

of I 2 yr

phase

and

Patients

of

the

in peripheral

20%

cytes

30%

as

blood
blastic

the results

as

CML

being

or bone
blood

in

the
the

patients

the survival

initial

blastic

at diagnosis:

marrow;

(B)

50%

involvement
are the
60 males.

blasts

instance,

subject
Median

of

analysis.

phase

when

(A)

blasts

plus promyelo-

in bone

(for

was

the criteria

at presentation

from
in

study

fulfilled

features
or

a single

198 1 ),cytogenetic

excluded

following

in peripheral

extramedullary

diagnosed

( I 969-

or extramedullary)

considered

one

from

METHODS

of the latter

consequently

were

displaying

Nine

(medullary

were

system

all of
it was

as well
as to ascertain
et al.s staging
system
in

MATERIALS

in I 30 cases.

has

was to analyze

of different

ent at diagnosis
in a series of 121 CML
patients,
whom
had cytogenetic
studies.
In addition,

marrow;
lymph

or (C)

node).64

of the present
report.
age was 46 yr (range

8-89).
Diagnosis
typical
low

of

CML

peripheral
leukocyte

some

was

All

patients

in
since

were

alive,

and

mo).

Death

cases.
related

uniformly
of

was

vascular

out

due

to ascertain
injuries

picture

(LAP)

treated

blastic

criteria:

in addition

score.

The

Banding
with

phase.

Ph

to a

chromo-

techniques

busulfan

In

myocardial

62

time

died

aplasia

after

(I

case).

patients,

Blood.

given

At

were

diagnosis
additional

every

when

were

dead,

patients
diagnosis

the
52

(range

2-57

90%

of the

complications
severe

3 mo.

the time

in over

from

somehow

infection

(3 cases),

( I case each). Although

infarction

the contribution
in elderly

mo.

from

patients,

transformation

patients

marrow

1981),

some

24
were

was 45.7

(June

to blastic

remaining
and

conventional

(88.5%).

of the series

carried

to CML:
cerebri

difficult

phosphatase

7 lost to follow-up

The

the

marrow

and 6-mercaptopurine

survival
was

on

bone

1979.

of vincristine

analysis

based

and

107 cases

appearance

Median

ictus

alkaline
only

the

was

blood

present

performed

courses
the

and

patients

the

prognostic

including

0.001).

<

patients

CML

II (intermediate

with

been performed.
aim of the present

until
From

(p

the

Ph-positive

factors;

of the

From
to

of patients).

stage

two

5%.

factors

of

32%

patients

The remaining
I 2 1 patients
There
were 61 females
and

facts make it difficult

to compare
survival
results
different
series.
Recently,
Tura
et al.4 have

Such
from

with

significant

of CML

Of

ones.355 This
that Ph-negative

risk,

in periph-

over

these

staging

I (low

in survival

highly

of

or no factors;

including

institution

to

one

previously
not
The primary

of CML

(Ph)
chromosome
rapid evolution

phase than the Ph-positive

has led to the suggestion

30%).
difference

series

each

cases

precursors

myeloblasts

a clinical

one

including

The

marrow

stage

with

38%).

of erythroid

bone
of

derived:

was

FACTORS
has
systems in several
a major
role in

and
model.

patients
risk,

the

lable, or chronic
phase, which
is followed
after a
median
of about
3 yr by an acute or subacute
terminal
period,
the so-called
transformation
or blastic
phase.
To date,
no therapeutic
approach
has achieved
a
substantial
delay
in the universally
fatal outcome
of

presence

blood.

planning
the treatment
of such diseases.
In most
instances,
chronic
myeloid
leukemia
(CML)
displays
a
typical
biphasic
course,
with an initial,
easily control-

CML.3

Rozman

hepatomegaly.

minority

latter

Ciril

eral

considered
then

and

(CML)

analysis

multivariate

of

factors

laboratory

the

be

model)

prognosis

and

Factors

Leukemia

Cervantes

leukemia

121

apparent

patients.

(Coxs

clinical

Prognostic

Myeloid

Francisco

myeloid

(1 1 .5%)

group.

Ph-positive

analysis

of

univariate

patients

prognosis

different
chronic

series

series

Ph-negative
poor

of

diagnosis

of

of CML
it must

Vol.

60,

it is

to the development
be pointed

No.

out

6 (December),

of

that

1982

in

From www.bloodjournal.org by guest on January 27, 2015. For personal use only.

PROGNOSIS

OF CHRONIC

MYELOID

both

instances

death

from

high

leukocyte

counts

and/or

such

1299

LEUKEMIA

a cause

high

occurred

platelet

coincidently

with

1.0

count.

0.9

Parameters

Evaluated
patient

the following

cal data

In each

at diagnosis

were

clinical

features

peripheral
(Hb),

blood

platelet

tial,

such

and

features

parameters

in

Phi

(LDH),

nase

(SGOT),

as

acid,

(ESR);
of

urea
pyruvic

presence
of Ph

or

mosa-

biochemical

(BUN),

data

lactic

dehydroge-

oxalacetic

transami-

transaminase

(SGPT),

iron,

20

40

B)

and

Fig.
patients.

Methods

Actuarial
method

survival

probability

of Kaplan

compared

and

using

the

curves

Meier.8

log

were

Different

rank

test.9

plotted

according

curves

When

were

needed,

square

for

trend#{176}was computed.
The

cut-off

median

value

level

of each

and then

until

significance

eters

(for

parameter

cutting

was eventually

instance,

Hb)

was selected

at different
obtained.

reached

by starting

levels,

above

In this way,

significance

only

at its

and

below,

some

In order

to identify

showing

included

in a multiple

censored
series

survival
were

the most

prognostic

regression

developed

defined

at a value

0; spleen

palpable

1, not palpable
over

8%

(EPB),

present

(MM),

over 5%

staging

s8%

was

<8.5
(<1%)

0. In order

a binary

rather

whole

the

(L),

in blood
myeloblasts

the development
variables

working

I,

0; blood

precursors

for

than

8%
size

0; liver

0; marrow

to make

method

preferred

the

1, 8.5

0; erythroid

I, absent

for

of a

For the Ph-positive

but,

group,

logically,

the variables

cytogenetic

status

was

were

defined

not entered

(present

turn

until

insertion

the

of the

equation.

At

recommended
expressing

selection

regression

is determined

a measure

censored

forward

is satisfactory
by using

each

step,

the

times

times
in days

significance
and

Prentice,22

were

avoided

instead

used.

not

yet

in the

level
ties
as

of in months

in

order

of

value

as

regression

in uncensored

and

possible

by

of observation.

RESULTS

0.025),

Series

The univariate
analysis
eters to be associated
with

Ph1-negative

0.001

<

(p

and

Ph-positive

Fig. I bone marrow

0.005),
hepatomegaly
(p < 0.01)
(in both eases
,

),

<

when

and blood

0.05).
The prognostic
evaluated
at different

the organ

basophils

could

be

precurlower than
higher

significance
levels from

than

of spleen
the costal

between
palpable
and not palpable
spleen.
Likewise,
liver
size was evaluated
for prognosis
at different
em below
significance

the lack
important

the costal margin,

being obtained

palpaonly for

liver.
the

of the Ph
prognostic

multivariate
chromosome
factor

analysis

confirmed

as the single
in the
whole

most
series

(p
0.0008).
In addition,
three other parameters
kept
their prognostic
value: a palpable
spleen (p
0.0009),
bone marrow
mycloblasts
over 5% (p
0.02),
and
presence
of erythroid
precursors
in peripheral
blood
(p
0.02).
Ph-negative
patients,
when
compared
=

with the Ph-positive

ences in their clinical

positive
demonstrated
seven parama poor prognosis:
absence
of

53
p

group,
I 9 yr versus

0.06).

population,
characteristics,

(72%

predominance
Whole

180

As

as

<

was

<

Furthermore,

is computed.
far

(p

(p

a palpable

The

160

presence
(l%)
oferythroid
blood (p < 0.025),
Hb

in the same

variables

log likelihood

140

margin
(>15 cm, >8 cm, >4 cm, palpable,
not palpable). Although
significance
was reached
at the cut-off
level
of 4 cm below
the costal
margin,
a higher
significance
was achieved
when comparison
was made

in the regres-

inserts

was

of variables

by Kalbfleish

that

the maximum

importance

observation
such

procedure

of

was considered

cut-off
levels (>6
ble, not palpable),

sion model.
A stepwise

curves

continuous

with

variables.
way

8.5 g/dl

for

),positive

(Ph

Survival

the Ph chromosome
(p
myeloblasts
over
5%
(p < 0.005),
splenomegaly

were

to the model

variables

g/dl

those

study

I, not palpable

0; Hb

The

chromosome

palpable

1, :s5%

easier,

absent)

Ph

1.

felt by palpation),
sors in peripheral

far from

factors,

according

by Cox.2

I,

(1%)

system

versus

(S),

prognostic
in the univariate

analysis

as follows:

negative
basophils,

significant

significance

120

Ph-

organomegaly

param-

the median.
features

100

to the

statistically

chi

80

Ph+

concentration.

Statistical

60

MONTHS
CML
-

vitamin

myelo-

count,

glutamic

phosphatase,

pcOOOl

marrow

myeloblasts,

serum

nitrogen

(2)

differential
bone

as presence

(4)

3.36

semiquantitative

differential

as well

10(14)

0.89
2.98

its differen-

(3)

ratio,

percentage

blood

with

a 100-cell

(M/E)

patients;

glutamic

in

(1)

size;

58.64

biochemi-

liver

O/E

52(101)

concentration

(WBC)

rate

chromosome,

and

hemoglobin

cell count

in a 500-cell

alkaline

and

for prognosis:

spleen

precursors

Ph-positive

uric

nase

such

megakaryocytes,

the

including

and

sedimentation

promyelocytes
of the

icism

sex,

as myeloid-erythroid

of

and

hematologic,

and evaluated

blood

erythroid

erythrocyte

estimation
absence

white

of

such

cytes,

as age,

count,

percentage

count,

clinical,

recorded

OBSERVED

men

versus

showed
some differsuch as male sex

46%

in

the

Ph-

0.06)
and older
age (mean
age
43 1 7 yr in the Ph -positive
group,
=

From www.bloodjournal.org by guest on January 27, 2015. For personal use only.

1300

CERVANTES

Table

1 . Results

of the Univariate
Ph-Positive

Analysis

in the

to

Group

0.9

Median

No. of

Survival

Patients

OBSERVED

AND

ROZMAN

EXPECTED

25(48)

16.74

15(44)

23.26

O/E
149
0$4

0.8
OlE

(mo)

p<0.01

0.7
Spleen
1

Not palpable

23

71

047

Palpable

79

43

1.24

6.01

0.6

<0.025

0.5

2a.

Liver
Not palpable

52

57

0.70

Palpable

48

36

1.47

6.40

0.4
0.3

<0.025

0.2
Hb (g/dl)
>8.5

86

<8.5

56

12

0.1

0.91

33

2.20

4.90

<0.05

0.0
0

Erythroid

precursors

44

58

0.64

Present(1%)

48

42

1.49

57

0.83

>5%

15

28

2.43

s8%

87

54

0.96

>8%

33

1.91

CML

8.46

<0.005

ERYTHROID

1.35

>0.10

Fig. 3.
Survival
curves
the presence
or absence
diagnosis.

50

57

0.85

44

42

116

ters;

100

120

53

55

0.96

>5%

41

44

1.05

0.09

g/dl

>0.10

<

IN BLOOD

PREQJRSORS

of Ph-positive
of erythroid

univariate

patients
precursors

analysis
five

(5)

IN BLOOD

PRECURSORS

demonstrated

splenomegaly

gin, p
megaly

promyelocytes

<5%

(Table

>2%

Ph -Positive

The

patients.

myeloblasts

myeloblasts

80

<0.01

basophils

<2%

Blood

60

NO ERYTHROID
71

Blood

7.01

myeloblasts

<5%

Blood

40

MONTHS

Absent

Marrow

20

in blood

(>4

according
in blood

in the

poor
cm

latter

prognosis

below

group
parame-

costal

the

to
at

mar-

0.05; palpable,
p < 0.025,
Fig. 2), hepato(L) (palpable,
p < 0.025),
Hb lower than 8.5

(p

<

erythroid

0.05),

precursors

in peripheral

blood
(EPB)
(I%)
(p<zO.Ol,
Fig. 3) and bone
marrow
myeloblasts
(MM)
over
5% (p < 0.005).
Table
I also includes
some of the information
regarding features
that did not reach statistical
significance
in the univariate
analysis.
The results of the multivariate
analysis
as well as the

Patients

Once
it was apparent
that Ph-negative
patients
could
be considered
a poor prognosis
group by themselves, irrespective
of the features
present at diagnosis,
the survival
analysis
was restricted
to Ph-positive

frequency
of the prognostic
factors
in the Ph-positive
group
are presented
in Table
2. When
splenomegaly
more

than

4 cm

ered,
significance
borderline
(p

below
in

0.1),

the costal

margin

the multivariate
whereas
a high

was consid-

analysis
significance

was
was

for a palpable
spleen (p
0.006).
Therefore,
(S) was eventually
considered
in the
multivariate
analysis
only when the spleen was palpable. As it can be seen, four variables
entered
the
regression
at the significant
level. Utilizing
these van-

obtained

splenomegaly

Table

2.

Results

of the Multivariate
Ph-Positive

Analysis

Level

of

Significance

20

40

60

80

100

120

Splenomegaly
Hepatomegaly

MONTHS

Erythroid
cML

PALBLE
.--

SPLEEN

NOT PALFBLE

Marrow

SPLEEN

Fig. 2.
Survival
curves
of Ph-positive
patients
according
the presence
or absence
of a palpable
spleen at diagnosis.

precursors
myeloblasts

in blood
>

5%

Hb<8.5g/dl
to

Significance
and frequency

of the variables

in the series.

Frequency

in the

Ph-Positive

Group

0.0064

77%

0.012

48%

0.066

52%

0.022

17%

p=0.38
of entry

in the

Group

analyzed

12%
by the reession

model

From www.bloodjournal.org by guest on January 27, 2015. For personal use only.

PROGNOSIS

ables,

OF CHRONIC

the following

created:

MYELOID

model

X(t)/X0(t)

0.52298
1.04238

(L
(MM

0.48)
0.17)

1301

for survival

EXP

LEUKEMIA

prediction

0.73760

0.88523
where X(t)

(5

was

0.77)

0.52)

(EPB

is the

hazard

85 of the 107 cases, the complete

dataset was available.
In the remaining
patients
the mean value in the series
was utilized,

xl

0.9

as suggested

xa for

1977

pO.OO1)

hand

:19.44

(dfB 1 ,p0.OO1)

0.7

>-

for het.,ogeneity=

(df-2,

0.8

rate

for survival
at time t and A0(t)
is the hazard
computed
at the average
values of the factors
in the model.
All
the patients
were used for the multivariate
analysis.
In

for the missing

parameter
Rosenman
et al.23

to

I-

0.6
0.5
0.4

0.

0.3

by

0.2
0.1

Staging

System

A staging

ofPh
system

as follows.

model

-Positive

Patients

was derived

from

For each patient

0.0

the multivariate
MONTHS

the loge of relative

hazard
rate
(flz in Coxs
notation)
was computed.
Figure
4 shows
the scores
obtained
in this way for the
Ph-positive
patients.
According
to such a score, three
subgroups
risk group

without
overlapping
of patients,
integrated

were observed:
by cases with

a lownone or

only
risk

one of the poor prognosis

factors;
an intermediatesubpopulation,
which
included
patients
showing
two
poor prognosis
features;
and a high-risk
group of
patients,
including
cases with three or four poor prog-

nosis

factors.

The

above

obtained
by assigning
Thus,
the low-risk

three

stages

I point to each
group
or stage

can

be easily

prognostic
I would

patients
with a score of 0 or 1 the
group
or stage II those patients
with

factor.
include

intermediate-risk
a score of 2, and

the high-risk
group or stage III those patients
displaying a score of 3 or 4. Stage I includes
32%, stage II
38%, and stage III 30% of the Ph-positive
patients.
The difference
in survival
of patients
belonging
to each
one

(x2
seen,

of

the

three

19.78, p
the O/E

II), or higher
of the

groups

was

highly

0.001,
Fig. 5, Table
ratio was lower (stage

3). As can be
I), equal (stage

<

(stage III)

intermediate-risk

than

1 That

was similar

Fig. 5.
patients.

Survival

survival

STAGE

5TE

II
III

curves

of

mo)

45

to

(median

STAGE I
STAGE II
STAGE Ill

the

that

three

stages

of Ph-positive

the

whole

population,

of

whereas survivals
of the low-risk
were longer or shorter
(median
At

respectively).

5 yr

and high-risk
patients
survival
86 and 28 mo,

from

probability
15% for

is 70% for stage

stage II and stage

Among
between

stage
those

diagnosis,

the

survival

I patients,
versus 30% and
III patients,
respectively.

I patients,
a comparison
was made
with a palpable
spleen and the remain-

ing (i.e., those with

the other
factors),

either no prognostic
and no difference

observed.
When
the staging
system
proposed
was applied
to the present series, there
cally
significant
(p > 0.10) (Fig.

difference
6).

is to say, survival

patients

significant

-.-.-.-.-.-.-

STAGE

factor or one of
in survival
was
by Tura
et al.
was no statisti-

between

the

stages

DISCUSSION
The

fatal

outcome

of

CML

has

estimulated

the

analysis
of prognostic
factors
in this disease.35
However, there is no agreement
on the prognostic
value of
different
feature,

findings
at diagnosis,
i .e., Ph -negativity.35

except
for a single
The strongest
prog-

in the present
series, as confirmed
analysis,
was also the absence

nostic
factor
multivariate
Table

3.

Log-Rank

Analysis

of the Survival

of

by the
Ph-

Curves

Observed
Expected

OlE

Stagel

10(34)

21.38

0.47

Stagell

21 (41)

21.07

1.00

StageIll

21 (32)

9.55

2.20

Total

52(107)

(Total)

0
-t6

-a4

+1.6

+0.6
kg#{149}
(RELATPIE

Fig. 4.
Population
distribution
ing to the log#{149}(relative hazard).

of Ph-positive

patients

HAZARD)

accord-

x2

heterogeneity

y2fortrend=

18.44(df=

1 9.78

52.00
(df

1;p<0.0O1).

2; p

<

0.00

1).

From www.bloodjournal.org by guest on January 27, 2015. For personal use only.

1302

CERVANTES

to
0.9

(df=2,p>0.10)

-,

Xfortrend:2.04

ROZMAN

prognosis,
in the univaniate
as well as in the multivariate
analysis,
confirming
previously
published
results.685
Both spleen and liver enlargement
reflect a
high tumor
burden.
However,
the lack of correlation
with
survival
of other
features
indicating
a great

Xforheterogenefty3fl

0.8

AND

mass

leukemic

(for

instance,

a high

leukocyte

count,

an increased
M/E
ratio,
or high
serum
vitamin
B,2 or uric acid) does not give support
an interpretation
of
influence
on prognosis
pointed

20

40

60

80

(=1

p>)

100

120

140

160

180

Fig. 6.
Survival
Tura et als stages.

I
II

TURAS

III
of Ph-positive

patients

according

to

evaluated
al.,#{176}
who
myeloblasts

filled
the
although
older age,
group of
negative

from
1 1.5%
range.

9% to 15%,
of Ph-negative
These patients

remains
Phpatients
is
otherwise
ful-

clinical
and laboratory
criteria
of CML,
a marked
predominance
of male sex and an
as reported
by others,7
was evident
in such a
patients.
The rather
different
course of PhCML,
with
a more rapid
evolution
to the

port
a

to the proposal
for considering
Ph -negative
distinct
entity.7
Thus,
after
excluding

negative
patients,
which
parameters

efforts should
are associated

in CML.

need

So, the

clones

ofelearly

negative

arises

a greater

CML
Ph-

number

which the aspirate

is carried
in general
a good
correlation

of

Factors
was a feature

poor
prognosis
in our series,
as
multivaniate
analysis.
An evident
was observed

of the

degree

in the present
at diagnosis,

the

influence

findings,

blood

for a palpable

of enlargement.
series
displayed
as it is typical

associated
confirmed
prognostic
spleen,

Although

with

by the
signifi-

irrespective
most

higher
than
to survival

furthermore,

exists

the prognostic

value

with

that

peripheral

of such

a feature

has also previously

been reported
by
A parameter
that did not keep its prognostic
the multivariate
analysis
was a low Hb.
viously
been reported
as a poor prognosis

value
It

in

has prefactor
by

authors.5#{176}5

of our whole
series, such
value in the multivariate

analysis
prognostic

fact could
be explained
through
latter
population,
which
would

cance

to

prognostic

out and,

field.

enlargement

can be

could
be argued
that
depends
on the area in

it

not reach
univariate

Spleen

liver

leading

myeloblast
percentage
finding
negatively
related

Ph-positive
patients
being
evaluated
for prognostic
factors
in order
to achieve
accurate
conclusions
in this

Prognostic

and

Similarly,
some authors35
have recognized
marked
blood
basophilia
as a poor prognosis
factor
in CML.
Although
an increased
percentage
of blood basophils
was associated
with a poor prognosis
in the univariate

be directed
to identify
with a poor prognosis
for

marrow

in our patients.
Although
distribution
of blasts
in CML

some

blastic
phase,
makes
cytogenetic
status
the
most
important
prognostic
variable
in CML
and gives supas

spleen

5% was another

that, even after the

a minority
of CML

It is now recognized
of banding
techniques,

patients,
ranging
negative.7
Our
within
the above

workers,24

more abnormal
of the blast crisis.

of
As

for survival
in CML,
except
by Jacquillat
et
found
a poor prognosis
for percentages
of
+ erythroid
precursors
in blood over 5%.

A bone
chromosome.
application

possible
mechanism
the former
features.

the
of

in our series
was the presence
oferythroid
precursors
in
peripheral
blood. This feature
has previously
not been

TURAS

curves

of

A parameter

MONTHS
TURAS

by other

out

the source
development

levels
of
to such

patients

such a physical
finding
in CML,
the minority
of

patients
in whom
the spleen
was not sufficiently
enlarged
to be palpated
enjoyed
a better prognosis.
A
prognostic
value
for splenomegaly
has been reported
by some authors,24
but not by others.6 In our series,
liver
enlargement
was also associated
with
a poor

any
prognostic
analysis
of the

decreasing
borderline

the significance
prognostic
value

previous

male

sex,9

increased
myeloblasts

blood,4
influence
different
a recent
statement.

reports.

This

the smaller
size of the
probably
account
for

of a feature
already
in the whole series.

was

the

report

by

Sokal27

levels.5

of

were not associated

series,
in contrast
case

low or high
platelet
leukocyte
high
or granulated
precursors

or high LDH serum

of Ph mosaicism
authors.
However,

lost its
and did

even in the
patients.
This

significance
Ph-positive

There
were other features
which
with a poor prognosis
in the present
with

a feature
analysis

of old

age,#{176}

counts,57#{176}34
percentages
of
in peripheral
A good

prognostic

has also been reported

neither

our

results2526

give

support

to

such

by
nor
a

From www.bloodjournal.org by guest on January 27, 2015. For personal use only.

PROGNOSIS

OF CHRONIC

Staging

System

The

current

systems

MYELOID

trend

in

1303

LEUKEMIA

the

elaboration

of

staging

apply

aggressive,

life-threatening

therapies

patients
therapy

and
restrict
only to high

Ideally,
following
available

a staging
characteristics:
data,
(B)

account
be

series.

of CML
should
fulfill
the
(A) be based on a few easily
each
prognostic
feature
should

multivariate

the staging

applied

was

statistical

(C)

analyses

system

the

to

proposed

present

it

failed

obtained
in Tura et
those of the present

be pointed
out that a companidoes not seem appropriate,
as

includes

a mixture

patients
cytogenetic

of Ph-positive

together
studies.

with
The

a fourth
of
staging
sys-

from the present

analysis
isolates
with different
survival
probability

series
and satisfies
The reproductibility

its further
application
to
Anyway,
as the frequency
population
probably

is very
be made

to collect

a large

groups
in our

the above conditions,

A, B, and C.
of such a staging
system requires
other

series

of CML

number

with

in

patients.

general

in this
studies

of patients

and other
pertinent
studies,
analysis
could be performed.

of

in the

low, future progress

through
cooperative

in

by Tuna

series,

series

tem derived
of patients

of

on prognosis,

et als

and Ph-negative
patients
without

redundant
variables
and select only the
ones, (D) be reproducible
in different

When

al.4

modalities
patients.

to its influence

from

to avoid
important

Tura

system

in proportion

derived

order
most

such
aggressive
or intermediate-risk

series.
However,
it must
son between
both series

early

after diagnosis
in order to delay the development
f the
blast crisis. Such aggressive
therapies
are restricted
to
Ph-positive
patients.28
Thus, based on the latter fact,
it appears
a logical
approach
that a staging
system
of
CML
must be restricted
to Ph-positive
cases in order
to identify
at diagnosis
different
prognosis
groups
of

a different
prognohaving
taken
into

account
that the prognostic
factors
al.s series were very different
from

is to use a few easily

available
data. CML
is
not, however,
the ideal disease
for such an approach,
because
of the universally
recognized
discriminating
prognostic
importance
of the chromosome
study.
Furthermore,
the current
trend in the treatment
ofCML
is
to

groups of patients
with
failure
is not surprising,

separating
sis. This

field will
in order

chromosome

whom

multivaniate

ACKNOWLEDGMENT
We express

our

the University

gratitude

of Texas

et

us with

in

We also acknowledge

to the

System

the computer

program
Begona

Department

of Biomathematics,

Cancer

Center,

for kindly

of Coxs

multiple

regression

Ramirez

supplying
analysis.

for her secretarial

work.

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From www.bloodjournal.org by guest on January 27, 2015. For personal use only.

1982 60: 1298-1304

A multivariate analysis of prognostic factors in chronic myeloid leukemia

F Cervantes and C Rozman

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