Journal of the Egyptian Nat. Cancer Inst., Vol. 21, No. 3, September: 209-217, 2009
CA 125, a New Prognostic Marker for Aggressive NHL
IMAN A. ABD EL GAWAD, M.D.* and HANAN E. SHAFIK, M.D.**
The Departments of Clinical & Chemical Pathology* and Medical Oncology**, NCI, Cairo University.
A shorter disease-free survival was associated with
increased CA 125 (p<0.001).
ABSTRACT
Purpose: CA 125 was evaluated in the sera of patients
with aggressive NHL, together with LDH and ß2m, in a
trial to assess its value in the diagnosis and follow-up,
and to compare it to some prognostic factors.
Conclusion: CA125 was found to correlate with stage,
tumor bulk, involvement of more than 1 extranodal site,
and presence of effusion. Elevated levels of CA 125 and
LDH were found to predict decreased survival. Initial
measurement of CA125 may, therefore, provide valuable
prognostic information.
Subjects and Methods: The study included 78 newly
diagnosed patients with diffuse large B cell non-Hodgkin’s
lymphoma (DLBCL), with age range 18-60 years, and a
WHO performance status of 0, I or II, in addition to twenty
apparently healthy controls. All patients received CHOP
regimen for 6 cycles.
Key Words: CA125 – LDH – ß2m, NHL – DLBCL.
INTRODUCTION
Results: The levels of CA 125 and LDH were significantly higher in DLBCL compared to the control group
(p-value = 0.031 and = 0.009, respectively). Cutoff levels
used were 20U/ml, 310 U/L, and 2µg/l for CA125, LDH
and ß2m, respectively. CA125 serum level was high in
55%, LDH level in 72%, and ß2m level in 62% of patients.
Cancer antigen 125 (CA 125) is a 220kDa
glycoprotein expressed in normal tissues originally derived from coelomic epithelia such as
peritoneum, pleura, pericardium [1], epithelium
of the female genital tract, mucosal cells of the
stomach and colon, and mesothelial cells of
serous membranes [2,3].
As regards the stage, CA 125 was elevated in 17%,
52%, 80%, and 100% of patients in stage I, II, III, and
IV, respectively. CA 125 was elevated in 81.3% of patients
with bulky disease, in 83.3% presenting with involvement
of more than 1 extranodal site, and in 90% presenting
with effusion.
CA125 serum levels are used to monitor
response to therapy and for follow-up of patients
with ovarian cancer [1]. They may also be elevated in other malignant and nonmalignant
conditions [4,5]. Although elevated levels have
been reported in patients with non-Hodgkin's
lymphoma (NHL), its role as a prognostic factor
remained uncertain [6].
The highest levels of CA125, LDH, and ß2m were
observed in stage IV, and lowest in stage I (p-value <0.001,
0.005, and 0.154, respectively). There was also a significant
positive correlation between CA 125 and LDH (p-value
<0.001).
CA 125 showed specificity of 80% with 95% CI (5694), and LDH showed sensitivity of 72% with 95% CI
(60-81).
Non-Hodgkin's lymphomas (NHLs) are a
heterogeneous group of lymphoproliferative
malignant diseases with differing patterns of
behavior and response to treatment [7].
Complete response to treatment was achieved in 71.8%
of our patients. Survival at 24 months was 78.2%. There
was a statistically significant increase in survival in patients
with CA125 <20U/ml, patients with LDH <310U/L, and
patients with ß2m <2µg/l (p-value = 0.006, 0.025, and
0.042, respectively).
Many prognostic factors have been described
in aggressive NHL: B symptoms (fever, night
sweats, and weight loss), performance status,
age, serum lactate dehydrogenase (LDH) level,
serum ß2 microglobulin, tumor bulk, and number
of nodal and extranodal sites of disease [8].
Correspondence: Dr Iman Attia Abdel Gawad
Lecturer of Clinical Pathology, NCI,
imanaga70@yahoo.com
209
210
CA 125, a New Prognostic Marker for Aggressive NHL
Elevated serum CA125 levels have been
reported in patients with NHL, especially those
with advanced disease [9]. CA125 was reported
by Lazzarino et al. [1], to be a reliable biologic
marker for the staging and restaging of patients
with NHL.
The aim of this work is to study CA 125 in
the sera of patients with diffuse large B cell
lymphoma (DLBCL) in a trial to assess its value
in the diagnosis and follow-up, and to compare
it with some prognostic factors. CA125 will be
compared to LDH, and ß2m. The relation between CA125 and patients’ survival will also
be studied.
PATIENTS AND METHODS
Patients:
Patients included in this study were subjected
to careful history taking, clinical examination,
histopathological typing, and routine laboratory
investigations.
Fresh blood samples were obtained from
seventy-eight newly diagnosed patients with
DLBCL who presented to the outpatient clinic
of the medical oncology unit, NCI, Cairo University, over a period of eight consecutive
months from January to May, 2006. They were
47 males and 31 females with ages ranging
from 20 to 64 years. Blood samples were obtained from twenty apparently healthy volunteers as controls.
Eligibility requirements included patients
with histologically proven DLBCL, age from
18 to 60 years, a WHO performance status of
0, I or II.
All patients received CHOP regimen for 6 cycles:
• Cyclophosphamide: 750mg/m2 i.v. day 1.
• Doxorubicin: 50mg/m2 i.v. day 1.
• Vincristine: 1.4mg/m2 i.v. day 1 (maximum
2mg).
• Predenisone: 100mg/m2 p.o. days 1-5 [10].
A written consent was taken from all patients
according to the international ethics committee
guidelines.
Methods:
Serum samples were prepared and aliquoted.
All patients and control samples were subjected
to the following:
1- Routine laboratory investigations:
• Liver function tests (ALT, AST, ALP), kidney
function tests (urea, creatinine, uric acid), and
LDH using Beckman autoanalyzer CX9
(USA).
• Complete blood picture (CBC) using Coulter
Counter (USA).
2- CA125 using AxSYM enzyme immunoassay
(Abbott Diagnostics, USA) [11].
3- ß2m using AxSYM enzyme immunoassay
(Abbott Diagnostics, USA) [11].
Statistical analysis:
Data management and analysis were performed using the Statistical Analysis System
(SPSS) software. Comparison of groups with
respect to numerical variables was done using
the Mann Whitney test. The Kruskal Wallis test
was used to compare medians of 3 or more
independent groups. Pearson’s correlation was
used to measure the strength of association
between 2 numerical variables [12] . Overall
survival and progression-free survival were
estimated in all patients using the Kaplan-Meier
test.
All p-values were two sided. p-values ≤0.05
were considered significant. Sensitivity, specificity and diagnostic accuracy were the validity
measures used for testing the studied parameters
as diagnostic tools for NHL. The different cutoffs were chosen using the receiver operating
characteristic (ROC). The ROC curve was constructed by plotting sensitivity versus 1specificity. The curve was drawn through points
that represent different decision cut-off levels
[13].
RESULTS
Table (1) shows the patients’ characteristics.
Table (2) shows percentages of elevation of
the studied markers according to some prognostic factors.
Table (3) shows comparative analysis of CA
125, LDH, and ß2m serum levels in NHL and
control group. The comparison was statistically
significant for CA125 and LDH (p-value =
0.031 and = 0.009, respectively).
Iman A. Abd El Gawad & Hanan E. Shafik
Table (4) shows comparison between
CA125, LDH, and ß2m serum levels according
to the different stages. All parameters showed
the highest level in stage IV, followed by stage
III, then stage II, and lowest in stage I. The
comparison was statistically significant for only
CA125 and LDH (p-value <0.001, 0.005, respectively). For CA125, there was a statistically
significant difference between stage I & II,
between stage I & III, between stage I & IV,
between II & III, and between stage II & IV.
For LDH, there was a statistically significant
difference between stage I & III, between I &
IV, between II & IV, and between II & IV.
Table (5) shows comparison of CA125, LDH
and ß2m with some prognostic factors. As regards the presence or absence of bulky disease,
the results were statistically significant for the
three markers (p-value <0.001, <0.001 and
0.009, respectively). As regards involvement
of more than 1 extranodal site, the comparison
was statistically significant for CA125 and LDH
(p-value <0.001). On comparing the 3 markers
according to presence or absence of effusion,
the results were also statistically significant for
only CA125 and LDH (p-value <0.001, 0.002,
respectively).
CA125, LDH and ß2m showed no significant
results in relation to the presence or absence of
B symptoms (p-value = 0.238, 0.187 and 0.527
respectively).
On performing Pearson’s correlation between
CA125 and the other two markers LDH and
ß2m, and between CA125 and age, there was a
statistically significantly positive correlation
between CA125 and LDH (p-value <0.001,
r=0.607) (Fig. 1), and weak correlation between
CA125 and ß2m (p-value <0.001, r=0.398), but
no statistically significant result was obtained
between CA125 and age (p=0.381, r=0.101).
Table (6) shows measurement of diagnostic
performance of the different markers in NHL
patients. LDH showed high sensitivity of 72%
with 95% CI (60-81), and CA 125 showed high
specificity of 80% with 95% CI (56-94). However, there was no significant difference between
the 3 markers as regards sensitivity and specificity due to overlapping of their 95% CI. As
regards sensitivity, the 95% CI for CA125,
LDH, and ß2m was (43-66), (60-81), and (4972), respectively. As for specificity, 95% CI
was (56-94), (19-63), and (15-59), respectively.
211
Table (1): Patients characteristics.
n (%)
Sex:
Male
Female
47 (60.3)
31 (39.7)
Age (years):
Median : 43
Range : 20-64
Stage:
I
II
III
IV
23 (29.0)
29 (37.0)
10 (12.0)
16 (20.0)
Prognostic factors:
Involvement of more than
one extranodal site
Bulky disease
Effusion
B symptoms
24 (30.8)
16 (20.0)
10 (12.8)
27 (35.0)
CA125:
High
Low
43 (55.0)
35 (45.0)
LDH:
High
Low
56 (72.0)
22 (28.0)
ß2M:
High
Low
48 (62.0)
30 (38.0)
Table (2): Percentages of elevation of the studied markers
according to prognostic factors.
Stage
I
II
III
IV
Bulky diseaes (a)
More than 1
extranodal site (b)
Effusion (c)
Total
CA125
n (%)
LDH
n (%)
ß2m
n (%)
23
29
10
16
16
24
4 (17.0)
15 (52.0)
8 (80.0)
16 (100.0)
13 (81.3)
20 (83.3)
13 (56.0)
20 (69.0)
8 (80.0)
14 (87.0)
16 (100.0)
21 (87.5)
12 (52.0)
20 (69.0)
6 (60.0)
10 (62.0)
10 (62.5)
14 (58.3)
10 9 (90.0) 10 (100.0) 6 (60.0)
a: Elevation of marker in relation to presence of bulky disease.
b: Elevation of marker in relation to involvement of more than
1 extranodal site.
c: Elevation of marker in relation to effusion.
Table (3): Comparative analysis of CA125, LDH, and
ß2m serum levels in DLBCL patients and control group using the Mann-Whitney test.
Control group
N=20
NHL group
N=78
10.0
(9.0-11.0)
20.9
(7.6-49.0)
0.031*
LDH (U/L)
318.0
(300.5-342.0)
408.0
(267.0-588.5)
0.009*
ß2m (µg/l)
2.2
(1.6-2.7)
2.2
(1.8-2.7)
0.764
CA125 (U/ml)
p-value
* Significant.
Values are medians with interquartile ranges in parenthesis.
212
CA 125, a New Prognostic Marker for Aggressive NHL
Table (4): Comparison of CA 125, LDH and ß2m serum
levels according to stage using the Kruskal
Wallis test.
CA125
(U/ml)
LDH
(U/L)
7.3 c
(3.3-9.8)
382.0 b
2.0
(230.3-428.0) (1.4-2.4)
Stage II (n=29)
20.1 b
(7.6-23.0)
406.0 b
2.2
(254.8-513.0) (1.8-2.7)
Stage III (n=10)
47.0 a
(21.0-61.6)
480.0 a
2.3
(350.0-605.0) (1.8-4.0)
Stage IV (n=16)
57.5 a
650.0 a
2.3
(51.0-104.0) (468.5-842.3) (1.8-5.4)
<0.001*
0.005*
0.154
* Significant.
Values are medians with interquartile ranges in parenthesis.
Group medians sharing same letter are statistically insignificant.
Table (5): Comparison of CA 125, LDH and ß2m with
some prognostic factors of NHL using the
Mann Whitney test.
CA125
(U/ml)
LDH
(U/L)
ß2m
(µg/l)
Bulky disease
(n=16)
53.0
(47.0-68.0)
647.0
(583.0-814.0)
3.0
(2.0-4.3)
Non bulky
disease
(n=62)
13.9
(4.0-23.2)
389.0
(250.0-473.0)
2.1
(1.5-2.5)
<0.001*
<0.001*
0.009*
Pos invol
(n=24) (p)
49
(32.0-63.3)
614.0
(462.5-715.0)
2.3
(1.9-3.0)
Neg involv
(n=54) (n)
11.5
(4.0-22.7)
382.0
(247.5-439.0)
2.1
(1.5-2.6)
p-value
<0.001*
<0.001*
0.132
Effusion
(n=10)
63.3
(48.0-68.3)
650.0
(523.0-828.0)
2.8
(2.0-6.5)
No effusion
(n=68)
16.5
(7.0-35.0)
396.0
(255.0-486.0)
2.0
(1.6-2.6)
<0.001*
0.002*
0.065
p-value
p-value
CA 125
LDH
ß2m
cutoff
cutoff
cutoff
20 (U/ml) 310 (U/L) 2 (µg/l)
ß2m
(µg/l)
Stage I (n=23)
p-value
Table (6): Measurement of diagnostic performance of the
different markers in NHL patients.
*Significant.
Values are medians with interquartile ranges in parenthesis.
(p): Positive involvement of more than 1 extranodal site.
(n): Negative involvement of more than 1 extranodal site.
Sen %
Sen (95% CI)
Spe %
Spe (95% CI)
PPV
PPV (95% CI)
NPV
NPV (95% CI)
Diagnostic accuracy %
56
(43-66)
80
(56-94)
91
(79-97)
31
(19-45)
60
72
(60-81)
40
(19-63)
82
(71-90)
27
(12-45)
65
62
(49-72)
35
(15-59)
79
(66-88)
19
(7-35)
56
Sen: Sensitivity.
Spe: Specificity.
PPV: Positive predictive value.
NPV: Negative predictive value.
DA : Diagnostic accuracy.
95% CI: 95% confidence interval.
Response:
Complete response was achieved in 71.8%
of patients (56/78), while 28.2% were resistant
to chemotherapy.
Survival:
All patients were followed for 24 months,
median time of follow-up was 18 months.
Survival at 12 months was 83.3%, and at 18
months 75.9%. Median survival was not
reached. Patients with CA125 <20U/ml, LDH
<310U/L, and ß2m <2µg/l showed a statistically
significant longer overall survival than those
with higher levels (p-values = 0.006, 0.025, and
0.042, respectively) (Figs. 2,3,4).
As regards disease-free survival (DFS), 22
patients were not eligible for analysis as they
were resistant to treatment, so DFS analysis
was done for 56 patients only. Median time to
progression was not reached. At 12 months,
16.4% of patients relapsed, and at 18 months
23.2% of the patients relapsed (Fig. 5). There
was a statistically significant difference in disease free survival between patients with CA125
<20U/ml compared to those ≥20U/ml, (p-value
<0.001) (Fig. 6). As regards LDH and ß2m,
there was no statistically significant difference
in disease free survival between patients with
LDH <310U/L compared with those with LDH
≥310U/L (p-value = 0.747) and with ß2m
<2µg/l, and those with a value ≥20µg/l, (pvalue = 0.11).
Iman A. Abd El Gawad & Hanan E. Shafik
213
Survival Functions
1.0
200
0.8
CA125
150
0.6
100
CA125
High
Low
High-censored
Low-censored
0.4
50
0.2
0
0.0
0
500
1000
LDH
1500
Fig. (1): Correlation between LDH, and CA125. p<0.001
& r=0.607.
3
6
Survival Functions
0.8
0.8
0.6
0.6
LDH
High
Low
High-censored
Low-censored
0.0
3
6
9
0.2
0.0
21
24
Fig. (3): Overall survival (OS) according to LDH. p=0.025.
3
6
9
0.8
0.8
0.6
0.4
0.2
12.00
CA125
High
Low
High-censored
Low-censored
0.4
0.0
18.00
24
0.6
0.2
Survival function
Censored
6.00
21
Survival Functions
1.0
Cum Survival
Cum Survival
Survival Functions
0.00
12 15 18
OS (Months)
Fig. (4): Overall survival (OS) according to ß2m. p=0.042.
1.0
0.0
24
ß2m
High
Low
High-censored
Low-censored
0.4
12 15 18
OS (Months)
21
Survival Functions
1.0
0.2
12 15 18
OS (Months)
Fig. (2): Overall survival (OS) according to CA125.
p=0.006.
1.0
0.4
9
24.00
DFS (Months)
Fig. (5): Disease-free survival (DFS) for the 56 analysed
patients. Median DFS not reached.
0.00
6.00
12.00
18.00
24.00
DFS (Months)
Fig. (6): Disease-free survival (DFS) in relation to CA125.
p<0.001.
214
CA 125, a New Prognostic Marker for Aggressive NHL
DISCUSSION
Although it is clear that CA125 is not a
product of lymphoma cells, elevated serum
levels in approximately 40% of NHL patients
at diagnosis, and the fact that in most series
levels directly correlate with certain features
of the disease, such as stage, response to therapy,
and survival, suggests that initial and serial
measurements of the antigen may provide prognostic information of value [14].
In this study, CA 125 and LDH were found
to be higher in the NHL group than in the control
group, both markers showed statistically significant elevation.
Consistent with our results, Dileki et al. [15]
found that the average CA125 level in NHL
patients was significantly higher than the controls (p<0.05) in their study done on 149 patients
and 26 healthy control subjects. The study group
included 69 non-Hodgkin lymphomas (NHL),
25 Hodgkin disease (HD), 20 acute myelocytic
leukemia (AML), 14 chronic lymphocytic leukemia (CLL), 12 chronic myelocytic leukemia
(CML), and nine multiple myeloma (MM) patients. CA125 was elevated in 37 of the NHL
patients and in none of the control subjects.
High serum CA125 levels were found to
correlate with mediastinal and/or abdominal
involvement, high tumor mass, and effusions,
reflecting the reaction of mesothelial cells to
the tumor [1]. Contrary to other serum markers
of established prognostic value in NHL related
to tumor load and proliferative activity, such
as ß2m and LDH activity, CA125 apparently is
not released by lymphoma cells. The mechanism
by which lymphoma stimulates CA125 production might be explained by mesothelial cell
stimulation via lymphokines derived from NHL
[1].
In the present study, CA125 serum level was
elevated in 55%, LDH in 72%, and ß2m in 62%
of patients. The highest elevation in the advanced stages of the disease was shown by
CA125, followed by LDH, then ß2m. CA125
was elevated in 81.3% of patients with bulky
disease, in 83.3% of patients presenting with
involvement of more than 1 extranodal site and
in 90% of patients presenting with effusion.
LDH was elevated in 100% of patients with
bulky disease, in 87.2% of patients presenting
with involvement of more than 1 extranodal
site and 100% of patients presenting with effusion. ß2m was elevated in 62.5% of patients
with bulky disease, in 58.3% of patients presenting with involvement of more than 1 extranodal site and in 60% of patients presenting
with effusion.
In a study by Jamal et al. [16], done on thirtyeight patients (24 with aggressive and 14 with
low-grade NHL), CA125 levels were elevated
in 46% of patients with aggressive NHL and
43% of patients with low-grade NHL.
Abdolmonem et al. [17], reported that serum
CA125 was elevated above the cut-off value
(30.1ng/ml) in 63.3% of patients in their study
done on 13 paediatric patients with NHL, and
9 with HD. Also Bairey et al. [7] measured
serum CA125 levels prospectively in 108 consecutive patients with NHL: 106 patients were
measured at diagnosis, 39 in remission and 7
in relapse. Levels were elevated in 43% at
diagnosis.
Wei et al. [18] reported that the rate of elevated serum CA125 for all patients was 59.1%
in their study done on 355 Chinese NHL patients. Aggressive lymphoma was diagnosed in
216 patients, indolent lymphoma in 87, and
undetermined histology in 32. A B-cell immunophenotype was demonstrated in 220 patients.
Also, Batlle et al. [19] studied serum levels
of CA125, LDH and ß2m in 200 NHL patients
with the following histologies: diffuse large Bcell lymphoma (DLBCL; n=95), low-grade
(n=66), and other (n=39). CA125 was elevated
in 43% of patients at diagnosis, LDH in 27%
and ß2m in 24%. CA125 was the only elevated
marker in 21% of patients.
Bonnet et al. [20], in a similar study carried
out on 99 newly diagnosed patients with NHL
and HD, found that CA125 serum levels were
elevated in 34% of patients, including 19% with
aggressive NHL, 45% with indolent NHL.
In a study carried by Benboubker et al. [21]
on 137 newly diagnosed NHL patients, serum
levels of CA125, LDH and ß2m were reported
to be elevated in 43%, 44%, and 22% of patients,
respectively, using cut-offs 25 IU/1, 300IU/1
and 3µg/1, respectively. LDH levels were higher
in intermediate or high-grade NHL, (61%) than
sCA125 (43%) or ß2m (23%), while in low-
Iman A. Abd El Gawad & Hanan E. Shafik
215
grade NHL 44% had increased sCA125, 23%
had increased LDH and 21% had increased ß2m
levels.
therapy and, in particular, of alternative therapy
for patients likely to die either from treatment
failure or treatment-related toxicity [21].
In this study, CA125, LDH, and ß2m all
showed the highest level in stage IV, followed
by stage III, then stage II, and lowest in stage
I. Significant results were only obtained for
CA125 and LDH (p-value <0.001 and 0.005,
respectively). When comparing the 3 markers
with bulky disease, all comparisons showed
significant results, while when comparing them
for the involvement of more than 1 extranodal
site and effusion, only CA125 and LDH showed
statistically significant results, and when comparing them with the presence or absence of B
symptoms, no significant results were found
for the three markers.
In the present study, complete response was
achieved in 56 patients (71.8%).
Consistent with these results, Abdolmonem
et al. [17] found a statistically significant higher
mean level of CA125 in advanced stage (III
and IV) paediatric NHL patients compared to
stage II, yet LDH levels did not reach statistical
significance. Also, in a study done by Bonnet
et al. [20] , univariate analyses showed that
CA125 levels correlated with poor performance
status, the presence of B symptoms, and advanced clinical stage.
Several other similar studies also reported
that high CA125 in NHL patients were associated with advanced clinical stage of disease,
bulky disease, B symptoms, a greater number
of extranodal sites, marrow involvement, pleural
or peritoneal effusions, poor performance status
and high LDH. They suggested that CA125
might be used as a marker to predict prognosis,
and to detect advanced disease in NHL [7,1518,21].
In the present study, a positive correlation
was found between CA125 and both LDH and
ß2m. In agreement with these results, Bairey et
al. [7] and Bonnet et al. [20] both reported that
elevated serum levels of CA125 were found to
correlate with high serum LDH levels and high
serum ß2m levels.
However, the majority of NHL patients die
from disease progression, regardless of histological sub-type. The identification of pretreatment variables that correlate with response
to therapy, duration of remission and survival
should lead to the rational selection of initial
Survival at 24 months was 78.2%. Patients
with CA125 <20U/ml, LDH <310U/L, and ß2m
<2µg/l all showed a statistically significant
longer overall survival than those with higher
levels (p-values = 0.006, 0.025, and 0.042,
respectively).
A shorter disease-free survival was associated with increased CA125 (p<0.001).
Consistent with the results of this study,
Batlle et al. [19] reported that a CR was achieved
in 61% of patients with normal CA125 and in
45% of patients with elevated levels (p=0.033).
Further-more, elevated serum CA125 at diagnosis was associated with shorter OS (p=0.025).
Also, Abdolmonem et al. [17] , in their study
reported that none of patients who had normal
serum CA125 at diagnosis died of their disease
during a mean follow-up duration of 9±4.1
months compared to 21.4% mortality (3/14) in
those who had high levels (p=0.002). Wei et al.
[18], as well, reported that the esti-mated 5.5year OS was 65% for patients with a normal
CA125 level and 25% for those with an elevated
serum level, a result which was statistically
significant.
Also, Bairey et al. [7] reported that normal
serum CA125 levels at diagnosis had strong
association with event-free and overall survival
(p=0.01 and 0.003, respectively), while patients
with increased levels had worse survival. Patients with high CA125 levels at diagnosis who
achieved remission showed a significant decrease in CA125 levels in remission.
Similarly, Jamal et al. [16] found in their
study that complete response occurred in 86%
of patients with normal CA125 levels and in
59% of patients with elevated CA125 levels.
In both aggressive and low-grade NHL, the
estimated 5-year overall survival rate was higher
in patients with normal CA125 levels than in
patients with elevated CA125 levels (88% versus
50% and 70% versus 27%, respectively). Bonnet
et al. [20], as well, performed a univariate analysis; they found that high CA125 levels corre-
216
CA 125, a New Prognostic Marker for Aggressive NHL
lated with poor performance status (PS). In his
univariate analyses, OS and DFS were affected
by poor PS, B symptoms, advanced clinical
stage, bone marrow involvement, low Hb, high
CRP or ß2-microglobulin levels. Age and abdominal involvement affected only DFS. CA125
level did not affect OS and DFS.
On the other hand, Benboubker et al. [21]
reported that with a median follow-up of 35
months, the significant univariate biological
prognostic parameters for five-year overall
survival of all patients in their study were found
to be s-LDH level (p<0.0001), ß2m level
(p=0.005) and sCA125 level (p=0.021). When
they separated intermediate, high-grade NHL
and low-grade NHL, sCA125 was not of prognostic value in the high-grade NHL group
(p=0.63), but was predictive of five-year survival of patients with low-grade NHL (94% Vs.
53%; p=0.0012).
Conclusion:
CA125 was found to correlate with stage,
tumor bulk, and involvement of more than 1
extranodal site, presence of effusion, response
to therapy, and survival, which suggests that
initial measurements of the antigen may provide
prognostic information of value. CA125 showed
high specificity, and LDH showed high sensitivity. Elevated levels of CA125, LDH, ß2m
were found to predict decreased survival. These
results indicate that serum CA125 level is frequently increased in a subgroup of patients with
NHL and correlates with a poor outcome in
patients with aggressive NHL. It appears more
predictive for this subgroup of patients and we
propose a new serologic prognostic index combining sCA125 and LDH levels in patients with
aggressive NHL.
More studies are recommended with a larger
number of patients and with serial measurements
of CA125 in addition to LDH.
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