lymphocytic leukemia and leukemic immunocytoma

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1985 65: 134-141

Prognostic information from cytogenetic analysis in chronic Blymphocytic leukemia and leukemic immunocytoma G Juliusson, KH Robert, A Ost, K Friberg, P Biberfeld, B Nilsson, L Zech and G Gahrton

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Prognostic

Information

From

B-Lymphocytic By

the

mia

with

peripheral 22

(CLI).

cytic

29

had

was

not

chromosome patients

had

showed

only

sole

patient

normal

There

not

was

IC groups

as

1 2 together + 1 2. and

The

1 2 patients

cytogenetic

between

significant

difference clinical

Eleven

and

between

findings

and

prognosis. therapy-free

and

complex

more

ered

(P

prognosis.

How-

(P

.005

and

stronger @ 1985

.002.

aberrations) with

with

changes were

were

consid-

A multivariate

strong

or

+ 12 normal

differences

IC patients

Rai

a

karyotypic

latter

as

survival Patients

Patients

respectively). was

advanced

predictor by Grune

of ‘).

clonal

with

only

+ 12

aberra-

10

patients

These

=

P

prognostic associated

.2)

.42

seven

evaluated considered

was two

were

Iftherapy-free probabilities

of

survival for the

groups

.87 (P = .09). the five-year

probability

Eleven patients revealed only normal karyotypes in more than I 2 metaphases studied. In cultures from I 2 patients without clonal aberrations the mitogens used

the

could

cultures were for cytogenetic

following

cytogenetic

be

therefore evaluacorrelation was seen subgroups:

(A) patients with + I 2, (B) patients with chromosomal aberrations other than + I 2, (C) patients with normal karyotype, and (D) uncharacterized patients. Patients in groups B and C had less splenomegaly than those in groups

A and

Diagnosis

D (P

and

.05).

=

Chromosome

Both PLL patients other clonal aberrations. diagnosis subgroup

(Table

Prognostic The within

had

and karyotype pattern was

groups

Correlations +del(3)(pl3) together with No other correlation between was similar

seen. The cytogenetic in the CLL and IC

2). Implications

of Karyotype

number of the cell clones

clonal chromosomal aberrations was found to be of great prognos-

tic importance. The more clonal aberrations found, the poorer was the prognosis, both regarding survival (P = .04) and therapy-free survival (P < l0; Fig I). Patients aberrations)

with had

of the disease Table

complex karyotypes a significantly more

than

patients

2.

Cytogeneti

with

less

c Subgro

(at least aggressive

clonal course

than

clonal

three

up Pattern No.

of Patients

CLL

IC

Other

Total

Total

No.

22

29

4

55

Total

evaluated

17

22

4

43

Total

with

12

16

4

32

2

3

1

6

4

7

0

i 1

6

6

3

15

clonal

aberrations

+l2alone +

1

2 with

Clonal

other

aberrations

aberrations without

+ 12


138

JULIUSSON

ProbabIlIty free

of therapy-

ProbabIlIty

of

ET

AL

therapy-

free survIval

survIval

I .0

1.0

0.5

0.5

N

Years 1

2

3

4

5

6

Yiars

7

2

Fig 1 . Actuarial therapy-free survival for all patients subdivided according to the number of clonal aberrations. N. normal karyotype (N = 1 1 ); 1 . single aberration (N = 1 6); 2. two aberrations (N 9); 3. three aberrations or more (N = 7): p < 10 . Small bars on curves indicate end of observation time for untreated patients.

Fig

3.

vided without

p=

in adequate

numbers

of evaluable

meta-

phases (P .007 with regard to survival, Fig 2; P < l06 with regard to therapy-free survival, Fig I). Patients with + I 2 did significantly worse than patients lacking this aberration; + I 2 patients required treatment earlier than ( I ) patients with other clonal =

aberrations (irrespective of the number of aberrations) (P .006, Fig 3), (2) patients with a normal karyotype (P .01 (3) all cytogenetically evaluated patients without + 12 (P .0005), and (4) all other patients =

=

),

=

(P .0001). These nounced when only

differences were the IC patients

=

(Fig larly

4). IC patients frequent and

with than

(I) +

with early

IC patients I 2 (P .002), =

even were

more proconsidered

1 2 demonstrated need for treatment

a particucompared

+

with (2)

clonal abnormalities IC patients with

other a normal

karyotype (P = .005), (3) all cytogenetically evaluated IC patients with + 1 2 (P .0001 ); and (4) all other IC patients (P < l0). Within the somewhat smaller CLL group, these differences were not significant.

to

other

excluding

(N

with leukemic cell clones metaphases were found

in which too few showed a signifi-

=

better

15).

prognosis

survival than (P .01, Figs Except

of survIval

with

for

for the study

karyotype, the small to reveal

an

regarding

observed significant

to

therapy-free

evaluable

karyotype

the complexity

number of differences

(P

=

between

poor

.01 1) or Binet25

+ 1 2 was the therapy, with

stag& (P bin count lymphocyte

=

(P

of the

deaths was too in survival with

strongest a P value

survival

and

.019)

stage.

=

marker of .05).

Rai’

Furthermore,

for disease compared

demanding with Rai

(P .002), count (P =

=

hemoglo.03) and

DISCUSSION

Cytogenetic give prognostic abnormal

analysis has information

karyotype of

had

a

been Patients

poorer

shown with

survival,32

to an and

therapy-

.f.-..-

survIval --

previously in CLL.

.

:

‘

-

U

A

0.5

-

‘

.

.

.

.

.

1

2

3

4

5

6

7

Years

Fig 2. Actuarial survival according to cytogenetic subgroup. N. normal karyotype (N = 1 1); + 12. + 12 with or without other aberrations (N 1 7); A, abnormal karyotype excluding +12 (N = 1 5); >3. three aberrations or more (N 7). (these patients are also included in either subgroup + 1 2 or subgroup A).

-

L1

+12

-‘3

=

subdi-

=

correlation

tree

-:,

patients

1 2. + 12 with or abnormal karyotype karyotype (N = 12).

the log rank3#{176} analysis. However, using Cox’s multivariate regression test3’ in the CLL and IC groups, the finding of + I 2 was significantly associated with poor survival (P .017). This should be compared with the

1.0

::

all +

regard

patients with 3 and 4).

=

ProbabilIty

ProbabIlIty

survival

subgroup. (N = 1 7). A. U. uncharacterized

7

.0001.

=

Patients evaluable

6

cytogenetic

aberrations

+12

5

4

therapy-free

according

cantly aberrations

Actuarial

3

.

1

.

, 2

N+A

+12 .

.

.

‘

,

3

4

5

6

7

Years

Fig 4. Actuarial therapy-free survival for IC patients only. subdivided according to cytogenetic subgroup. + 1 2. + 1 2 with or without other aberrations (N = 1 0); N + A. normal karyotype or abnormal karyotype excluding + 12 (N 12); U. uncharacterized karyotype (N = 7). P < i0’.

=


CHROMOSOMES

AND

PROGNOSIS

IN

CLL

AND

IC

139

patients with + I 2 had a more rapidly progressing disease and required early treatment.23’33 In the present, more extensive study, we have further examined the

prognostic

implications

of the

and its relation to the lymphocytic lymphomas. revealed indicator

karyotypic

Kiel class4 of A multivariate

pattern

leukemic Banalysis

that the + I 2 aberration was as of poor prognosis as advanced Rai’

stage.

However,

the complexity

the greatest present data typing

prognostic seem to

present

of the karyotype

importance

be emphasized

material

had

strong an or Binet25 was of

importance. Furthermore, the indicate that the cytogenetic

is of prognostic

group. It should

some cases + I 2 can be a secondary aberration. This is supported by the finding in PLL cells.37 However, it cannot be excluded that + 1 2, although present in the primary clone, can be lost during further clonal evolu-

mainly

that

the

a somewhat

in the

IC

better

IC

group

in the

prognosis

than

tion. This problem repeated cytogenetic disease

in some

is currently typings

of our

under during

of clonal aberrations prognostic marker.

types

clonal

(at

least

was here Complex

aberrations)

were

found to karyo-

strongly

with an aggressive disease ( Fig I P .007). This is consistent with previous ,

=

by of the

patients.

The number be an important ciated 2, P

investigation the course

I0 data