Journal of Cancer Therapy, 2013, 4, 452-459
http://dx.doi.org/10.4236/jct.2013.43A055 Published Online March 2013 (http://www.scirp.org/journal/jct)
Absolute Lymphocyte/Monocyte Ratio at Diagnosis and
Interim Positron-Emission Tomography Predict Survival
in Classical Hodgkin Lymphoma
Luis F. Porrata*, Kay M. Ristow, Thomas M. Habermann, Thomas E. Witzig, Joseph P. Colgan,
David J. Inwards, Stephen M. Ansell, Ivana N. Micallef, Patrick B. Johnston, Grzegorz Nowakowski,
Carrie A.Thompson, Svetomir N. Markovic
Division of Hematology, Internal Medicine, Mayo College of Medicine, Rochester, USA.
Received January 15th, 2013; revised February 17th, 2013; accepted February 26th, 2013
ABSTRACT
Interim Positron-Emission Tomography (int-PET) and the peripheral blood absolute lymphocyte/monocyte ratio at di-
agnosis (ALC/AMC-DX) have been shown to be predictors for progression-free survival (PFS) and time to progression
(TTP) in classical Hodgkin lymphoma (cHL). Therefore, we studied if the combination of ALC/AMC-DX and the
(int-PET) can further stratified PFS and TTP in cHL patients. Patients were required to be diagnosed, treated, and fol-
lowed with int-PET at Mayo Clinic, Rochester, Minnesota. From 2000 until 2008, 111 cHL patients qualified for the
study. The median follow-up was 2.8 years (range: 0.3 - 10.4 years). Patients with a negative int-PET (N = 98) pre-
sented with a higher ALC/AMC-DX (median of 2.32, range: 0.26 - 37.5) compared with patients with a positive
int-PET (N = 13) (median of 0.9, range: 0.29 - 3.10), p < 0.004. By multivariate analysis, ALC/AMC-DX and the
int-PET were independent predictors for PFS and TTP, when compared with the International prognostic Score. Patients
were stratified into four groups: group 1 included patients with a negative int-PET and ALC/AMC-DX ≥ 1.1; group 2
included positive int-PET and ALC/AMC-DX ≥ 1.1; group 3 included negative int-PET and ALC/AMC-DX < 1.1; and
group 4 included positive int-PET and ALC/AMC-DX < 1.1. Group 1 experienced superior PFS and TTP in compari-
son with the other groups. In conclusion, the combination of ALC/AMC-DX and the int-PET provides a simple model
to assess clinical outcomes in cHL.
Keywords: Classical Hodgkin Lymphoma; Absolute Lymphocyte/Monocyte Ratio at Diagnosis; Interim PET-Scan;
Progression-Free Survival; Time to Progression
1. Introduction
The peripheral blood absolute lymphocyte/monocyte ratio
at diagnosis (ALC/AMC-DX), as a surrogate biomarker
of host immunity (i.e., ALC) and tumor microenviron-
ment (i.e., AMC), has been recently reported to be a pre-
dictor for overall survival, lymphoma-specific survival,
progression-free survival, and time to progression in clas-
sical Hodgkin lymphoma (cHL) [1,2]. Interim Positron-
Emission Tomography (int-PET), as a functional imaging
test for tumor activity, has been shown to be a predictor
for progression-free survival (PFS) and time to progres-
sion (TTP) in cHL [3]. Romano et al. [4] reported that
even though the ALC/AMC ratio correlated with prog-
nosis, the int-PET was better discriminator of survival
than the ALC/AMC ratio.
Therefore, in an attempt to validate Romano’s findings,
we studied if the ALC/AMC-DX is an independent pre-
dictor in comparison with the int-PET for PFS and TTP
and if the combination of ALC/AMC-DX and the int-
PET can further stratified the clinical outcomes of PFS
and TTP in patients with cHL.
2. Patients and Methods
2.1. Patient Population
In order to participate in the study patients were required
to have newly diagnosed cHL, treated with adriamycin,
bleomycin, vinblastine, and dacarbazine (ABVD) with or
without radiation, had an int-PET before cycle number 3,
and be followed at the Mayo Clinic, Rochester, Minne-
sota.
Patients diagnosed with nodular lymphocyte predomi-
nant Hodgkin’s lymphoma, treated only with radiation or
palliative care, positive for human immunodeficiency
*Corresponding author.

Absolute Lymphocyte/Monocyte Ratio at Diagnosis and Interim Positron-Emission Tomography
Predict Survival in Classical Hodgkin Lymphoma
453
virus and with concomitant autoimmune disease receiv-
ing immunosuppressive therapy were excluded. From
2000 to 2008, 111 consecutive cHL qualified for the
study. No patients refused authorization to use their me-
dical records for research and none was lost to follow-up.
Approval for the retrospective review of these patients’
records was obtained from the Mayo Clinic Institutional
Review Board and the research was conducted in accor-
dance with the USA federal regulations and the Declara-
tion of Helsinki.
2.2. End-Point
The primary end-point of the study was to assess if the
combination of ALC/AMC-DX and the int-PET can fur-
ther stratified the clinical outcomes of PFS and TTP in
patients with cHL.
The cut-off for the ALC/AMC-DX ≥ 1.1 used in this
study was based on our previous publication [1] and ob-
tained from the complete blood cell count (CBC) at diag-
nosis of cHL. The ALC/AMC ratio was obtained by di-
viding the absolute lymphocyte count (ALC) over the ab-
solute monocyte count (AMC) from the CBC at diagno-
sis [5].
2.3. Prognostic Factors
The prognostic factors evaluated in the study included
the International Prognostic Score (IPS) [6] at diagnosis
for advanced stage patients : [age > 45 years, albumin <
4 g/dl, ALC < 600/µl or < 8% of white cell count, hemo-
globin < 10.5 g/dl, male gender, stage IV, and white
blood cell count ≥ 15,000/µl]; treatment modality (com-
bination chemotherapy plus radiation versus chemother-
apy alone), limited versus advanced disease, AMC at diag-
nosis, ALC/AMC ratio at diagnosis, and interim PET-
scan.
2.4. Response and Survival
Definitions of response criteria, PFS, and TTP were ba-
sed on the guidelines from the International Harmoniza-
tion Project Lymphoma [7]. PFS was defined as the time
from cHL diagnosis to the time to progression, relapse
from complete response, death as a result of any cause,
or last follow-up. TTP was defined as the time from cHL
diagnosis to the time of lymphoma progression, death as
a result of lymphoma, or last follow-up.
2.5. Statistical Analysis
PFS and TTP were analyzed using the approach of Kap-
lan and Meier [8]. Differences between survival curves
were tested for statistical significance using the two-
tailed log-rank test. The Cox proportional hazard model
[9] was used for the univariate and multivariate analyses
to evaluate the variables under the prognostic factors’
section to assess their impact on PFS and TTP. Chi-
square tests were used to determine relationships be-
tween categorical variables. The Wilcoxon-rank test was
used to determine associations between continuous vari-
ables and categories, and Spearman’s correlation coeffi-
cients were used to evaluate associations for continuous
variables. All p values are two-sided associations and p
values less than 0.5 are considered statistically signifi-
cant.
3. Results
3.1. Patients Characteristics
The median age at diagnosis for this cohort of 111 cHL
patients was 37 years (range: 18 - 83 years). The distri-
bution of additional baseline characteristics for these pa-
tients is presented in Table 1. The median follow-up pe-
riod for the cohort was 2.8 years (range: 0.3 - 10.4 years)
and for living patients (N = 99) was 3.0 years (range: 0.3
- 10.4 years). Six patients died of causes not related to
lymphoma or the treatment of lymphoma, and 6 patients
did secondary to relapse/progression of lymphoma.
3.2. ALC/AMC-DX, Int-PET, and
Progression-Free Survival and Time to
Progression
Kaplan-Meier analysis was used to study the PFS and
TTP based on the ALC/AMC-DX and int-PET. Patients
with an ALC/AMC-DX ≥ 1.1 experienced superior PFS
(Figure 1(a)) and TTP (Figure 1(b)) compared with
patients with an ALC/AMC-DX < 1.1 [PFS: median was
not reached vs 8.6 years, 3-year PFS rates of 92% (95%
CI, 83% - 99%) vs 50% (95% CI, 18% - 80%), p <
0.0001, respectively; and TTP: median was not reached
vs not reached, 3-year TTP rates of 96% (95% CI, 87% -
100%) vs 55% (95% CI, 20% - 77%), p < 0.0001, re-
spectively]. Similarly, patients with a negative int-PET
also experienced superior PFS (Figure 1(c)) and TTP
(Figure 1(d)) compared with patients with a positive int-
PET [PFS: median was not reached vs 2.1 years, 3-year
PFS rates of 91% (95% CI, 85% - 98%) vs 45% (95% CI,
10% - 80%), p < 0.0001, respectively; and TTP: median
was not reached vs 2.1 years, 3-year TTP rates of 98%
(95% CI, 84% - 100%) vs 45% (95% CI, 10% - 82%), p
< 0.0001, respectively].
By univariate analysis (Table 2), both ALC/AMC-DX
and int-PET were predictors for PFS and TTP. Due to the
strong correlation between ALC (r = 0.5, p < 0.0001)
and AMC (r = −0.4, p < 0.0001), we only included the
ALC/AMC-DX in the multivariate analysis to prevent
co-linearity. Similarly, both age and stage are included in

Absolute Lymphocyte/Monocyte Ratio at Diagnosis and Interim Positron-Emission Tomography
Predict Survival in Classical Hodgkin Lymphoma
454
Table 1. Baseline patients’ characteristics at diagnosis.
Variables N (111) Median Range
Age, years, median (range) 111 (100%) 37 (18 - 83)
Gender
Female 51 (46%)
Male 60 (54%)
Absolute lymphocyte count at diagnosis × 109/l, median (range) 111 (100%) 1.38 (0.15 - 9.1)
Albumin (g/dl), median (range) 96 (86%) 4.0 (2.1 - 5.8)
Hemoglobin (g/dl), median (range) 111 (100%) 13.1 (9.0 - 17.2)
Absolute monocyte count at diagnosis × 109/l 111 (100%) 0.61 (0.21 - 2.61)
Stage
Limited 56 (50%)
Advanced 55 (50%)
WBC × 109/l 111 (100%) 8.5 (1.8 - 21.0)
Bulky disease
≥10 cm 2 (25)
<10 cm 109 (98%)
Treatment
Chemotherapy 63 (57%)
Chemotherapy + radiation 48 (43%)
IPS risk factors
Age in years
>45 39 (35%)
≤45 72 (65%)
Albumin (g/dl) (N = 96)
≥4 51 (53%)
<4 45 (47%)
Absolute lymphocyte count per µl
≥600 100 (90%)
<600 11 (10%)
Hemoglobin (g/dl)
>10.5 98 (88%)
≤10.5 13 (12%)
WBC × 109/l
>15 11 (10%)
≤15 100 (90%)
Stage 4
Yes 23 (21%)
No 88 (79%)
Number of IPS risk factors
0 13 (12%)
1 35 (32%)
2 35 (32%)
3 16 (14%)
4 9 (8%)
5 3 (2%)
IPS factors index
≥3 28 (25%)
<3 83 (75%)
PET-scan
Positive 13 (12%)
Negative 98 (88%)
Abbreviations: IPS = International Prognostic Score; PET = Positron Emission Tomography; and WBC = white blood cell count.

Absolute Lymphocyte/Monocyte Ratio at Diagnosis and Interim Positron-Emission Tomography
Predict Survival in Classical Hodgkin Lymphoma
455
(a) (b)
(c) (d)
Figure 1. (a) Progression-free survival based on absolute lymphocyte/monocyte count ratio at diagnosis (ALC/AMC-DX); (b)
Time to progression based on the ALC/AMC-DX; (c) Progression-free survival based on the interim positron emission tomo-
graphy (PET)-scan; (d) Time to progression based on the interim PET-scan.
Table 2. Univariate analysis for progression-free survival and time to progression.
Variables Progression-free survival Time to Progression
HR 95% CI p HR 95% CI p
Age > 45 years 3.52 1.30 - 10.35 <0.01 1.81 0.52 - 6.02 0.3
Albumin ≥ 4 g/dl 0.35 0.10 - 1.06 0.06 0.26 0.04 - 1.06 0.06
ALC ≥ 600 cell/µl 0.27 0.09 - 0.97 <0.04 0.15 0.04 - 0.58 <0.009
AMC ≥ 630 cells/µl 3.42 1.72 - 9.22 <0.02 3.70 1.06 - 12.31 <0.04
ALC/AMC-DX ≥ 1.1 0.13 0.05 - 0.35 <0.0002 0.07 0.02 - 0.24 <0.0001
Bulky disease ≥ 10 cm 3.74 0.21 - 18.76 0.3 6.08 0.33 - 33.10 0.2
Hgb < 10.5 g/dl 1.04 0.16 - 3.71 0.9 1.56 0.24 - 6.07 0.6
IPS Factors ≥ 3 4.14 1.54 - 11.60 <0.005 8.51 2.46 - 38.88 <0.0006
Limited disease 0.12 0.02 - 0.44 <0.0005 0.19 0.13 - 0.73 <0.01
Male 1.55 0.58 - 4.55 0.4 2.50 0.72 - 11.42 0.2
PET-scan negative 0.13 0.05 - 0.37 <0.0003 0.05 0.01 - 0.18 <0.0001
CT + RT vs CT alone 0.08 0.004 - 0.38 <0.0004 0.11 0.01 - 0.60 <0.007
Stage 4 2.40 0.81 - 6.48 0.1 2.35 0.61 - 7.83 0.2
WBC ≥ 15 cells/µl 1.65 0.33 - 29.80 0.6 1.04 0.21 - 20.26 0.9
Abbreviations: ALC = absolute lymphocyte count; AMC = absolute monocyte count; CT = chemotherapy; DX = diagnosis; Hgb = hemoglobin; IPS = Interna-
tional Prognostic Score; PET = Positron Emission Tomography; RT = radiation; and WBC = white blood cell count.

Absolute Lymphocyte/Monocyte Ratio at Diagnosis and Interim Positron-Emission Tomography
Predict Survival in Classical Hodgkin Lymphoma
456
the IPS, we only included IPS in the multivariate analysis.
In a multivariate Cox regression model (Table 3), both
ALC/AMC-DX and int-PET were the only two statisti-
cally significant independent predictors for PFS and TTP.
Since ALC/AMC-DX and int-PET were the only inde-
pendent predictors in the initial multivariate analysis, we
compared them in a subsequent multivariate analysis
adjusting for each of them separately. Both remained still
independent predictors for PFS [ALC/AMC-DX: HR =
0.51, 95% CI, 0.27 - 0.85, p < 0.005 and int-PET: HR =
0.24, 95% CI, 0.07 - 0.76, p < 0.02] and for TTP [ALC/
AMC-DX: HR = 0.42, 95% CI, 0.17 - 0.83, p < 0.006
and int-PET: HR = 0.11, 95% CI, 0.02 - 0.44, p < 0.002].
3.3. Association between ALC/AMC-DX and
Int-PET
Because in this cohort of patients, only the ALC/AMC-
DX and int-PET were the only independent predictors for
PFS and TTP, we set out to investigate if there was any
association between the ALC/ACM-DX and int-PET. By
the Wilcoxon-rant test, patients with a negative int-PET
(n = 98) presented with higher ALC/ AMC-DX (median
of 2.32, range: 0.26 - 37.5) compared with patients with a
positive int-PET (n = 13) (median of 0.9, range: 0.29 -
3.10), p < 0.004 (Figure 2). Ninety percent (88/98) of
patients with an ALC/AMC-DX ≥ 1.1 achieved a nega-
tive int-PET compared to only 10% (10/98) of patients
with an ALC/AMC-DX < 1.1, p < 0.0006.
3.4. ALC/AMC-DX and Int-PET Stratified
Groups
Because both the ALC/AMC-DX and int-PET were in-
dependent predictors for PFS and TTP, patients were
stratified into four groups: group 1 included patients with
a negative int-PET and ALC/AMC-DX ≥ 1.1; group 2
included positive int-PET and ALC/AMC-DX ≥ 1.1;
group 3 included negative int-PET and ALC/AMC-DX <
1.1; and group 4 included positive int-PET and ALC/
AMC-DX < 1.1. The three year PFS rates (Figure 3(a))
for each group were: 95% (group 1); 45% (group 2);
56% (group 3); and 50% (group 4), p < 0.0001. The three
year TTP rates (Figure 3(b)) for each group were: 100%
(group 1); 40% (group 2); 65% (group 3); and 50%
(group 4), p < 0.0001.
3.5. PFS and TTP Based on ALC/AMC-DX and
Int-PET by Limited/Advanced Stage
Because the IPS is only limited to advance stage cHL, we
analyzed if both the ALC/AMC-DX and int-PET are pre-
dictors for PFS and TTP based on limited/advanced stage.
Table 4 summarizes the univariate analysis for PFS and
TTP based on ALC/AMC-DX and int-PET according to
the sub-groups of limited stage and advanced stage. The
ALC/AMC-DX and int-PET were predictors for PFS and
TTP regardless of limited stage or advanced stage. We
also compared group 1 (negative int-PET and ALC/AMC-
Table 3. Multivariate analysis progression-free survival and time to progression.
Variables Progression-free survival Time to progression
ALC/AMC-DX ≥ 1.1 0.63 0.33 - 0.90 <0.04 0.16 0.03 - 0.63 <0.004
IPS Factors ≥ 3 2.47 0.83 - 7.60 0.1 1.72 0.58 - 8.80 0.5
PET-scan negative 0.22 0.07 - 0.71 <0.02 0.07 0.01 - 0.31 <0.0004
CT + RT vs CT alone 0.22 0.01 - 2.89 0.4 0.17 0.01 - 2.79 0.2
Abbreviations: ALC = absolute lymphocyte count; AMC = absolute monocyte count; CT = chemotherapy; DX = diagnosis; IPS = International Prognostic
Score; PET = Positron Emission Tomography; and RT = radiation.
Table 4. Univariate analysis based on ALC/AMC-DX and int-PET according to limited stage and advanced stage.
Limited stage Advanced stage
Progression-free survival
ALC/AMC-DX ≥ 1.1 0.07 0.01 - 0.21 <0.0007 0.58 0.33 - 0.95 <0.02
Int-PET negative 0.10 0.02 - 0.20 <0.002 0.26 0.09 - 0.82 <0.03
Group 1 versus other 0.04 0.01 - 0.18 <0.002 0.26 0.08 - 0.76 <0.01
Time to progression
ALC/AMC-DX ≥ 1.1 0.06 0.01 - 0.22 <0.0007 0.41 0.11 - 0.82 <0.007
Int-PET negative 0.11 0.03 - 0.21 <0.002 0.10 0.20 - 0.30 <0.002
Group 1 versus other 0.05 0.02-0.17 <0.002 0.05 0.01 - 0.30 <0.0003
Abbreviations: ALC = absolute lymphocyte count; AMC = absolute monocyte count; DX = diagnosis; group 1= negative int-PET and ALC/AMC-DX ≥ 1.1;
and PET = Positron Emission Tomography.

Absolute Lymphocyte/Monocyte Ratio at Diagnosis and Interim Positron-Emission Tomography
Predict Survival in Classical Hodgkin Lymphoma
457
Figure 2. Box plot showing patients with a negative interim
positron emission tomography (PET)-scan presented with
higher absolute lymphocyte/monocyte count at diagnosis
(ALC/AMC-DX) (median of 2.32, range: 0.26 - 37.5) com-
pared with patients with a positive interim PET-scan (me-
dian of 0.9, range: 0.29 - 3.10).
DX ≥ 1.1) versus other stratified groups described in the
above 3.4 sub-heading. The stratified group 1 was also a
predictor for PFS and TTP regardless of limited or ad-
vanced stage. Due to the small numbers of events by
each sub-group, multivariate analysis was not performed.
4. Discussion
The int-PET representing a functional imaging test for
tumor burden activity and the ALC/AMC-DX represent-
ing a surrogate biomarker for the interaction between
host immunity and tumor microenvironment have been
reported to predict clinical outcomes, specifically PFS
and TTP in cHL. We, therefore, combined the int-PET
and the ALC/AMC-DX as representative markers of the
interaction between tumor burden, host immunity, and
tumor microenvironment to further stratified clinical out-
comes in cHL.
To support the hypothesis that the combination of the
int-PET and the ALC/AMC-DX can further stratified
PFS and TTP in CHL patients, it was necessary to de-
monstrate that both int-PET and the ALC/AMC-DX were
independent predictors of PFS and TTP in cHL. In our
cohort, by univariate analysis, both the int-PET and the
ALC/AMC-DX were predictors for PFS and TTP. By
multivariate analysis, both the int-PET and the ALC/
AMC-DX remained independent predictors for PFS and
TTP when compared with the International Prognostic
Score, limited or advanced disease, and chemotherapy
with or without radiation. Because the int-PET and the
ALC/AMC-DX in cohort of patients were the only two
(a)
(b)
Figure 3. (a) Superior progression-free survival observed in
patients in group 1 compared with the other groups; (b)
Superior time to progression observed in patients in group
1 compared with the other groups. Group 1 = negative in-
terim positron emission tomography (PET)-scan and abso-
lute lymphocyte/monocyte count ratio at diagnosis (ALC/
AMC-DX) ≥ 1.1; group 2 = positive interim PET-scan and
ALC/AMCDX ≥ 1.1; group 3 = negative interim PET-scan
and ALC/AMC-DX < 1.1; and group 4 = positive interim
PET-scan and ALC/AMC-DX< 1.1.
independent predictors for PFS and TTP, this finding led
to investigate if there was any association between them.
Patients with a negative int-PET presented with higher
ALC/AMC-DX compared with patients with a positive
int-PET. Furthermore, ninety percent of patients with an
ALC/AMC-DX ≥ 1.1 achieved a negative int-PET. The
strong association between the int-PET and the ALC/
AMC-DX indirectly supports the crucial interaction be-
tween host immunity (i.e., ALC), tumor microenviron-
ment (i.e., AMC) and tumor burden (i.e., int-PET). To
further clinically support the importance of the interac-
tion between host immunity, tumor microenvironment
and tumor burden using the int-PET and the ALC/AMC-

Absolute Lymphocyte/Monocyte Ratio at Diagnosis and Interim Positron-Emission Tomography
Predict Survival in Classical Hodgkin Lymphoma
458
DX, we categorized the patients into four groups based
on positive versus negative int-PET and ALC/ AMC-DX
≥ 1.1 versus ALC/AMC-DX < 1.1. Patients in the group
with negative int-PET (low tumor burden) and ALC/
AMC-DX ≥ 1.1 (high host immunity and low immuno-
suppressive tumor microenvironment) experienced supe-
rior PFS and TTP in comparison with any other group
with any negative marker of high tumor burden, low host
immunity and/or immunosuppressive microenvironment.
A limitation of the IPS is that it only applies to cHL
patients with advanced stage and not to limited stage
cHL patients. Thus, we investigated if the ALC/AMC-
DX and the int-PET are prognostic factor for PFS and
TTP according to the stage at diagnosis. We identified
that both the ALC/AMC-DX and int-PET were predic-
tors for PFS and TTP for cHL patients with limited stage
and advanced stage. Furthermore, the prognosis for PFS
and TTP for patients with a negative int-PET and an
ALC/AMC-DX ≥ 1.1 was superior to any group regard-
less of limited or advanced stage, suggesting that the
combination of ALC/AMC-DX and int-PET can help to
predict clinical outcomes in cHL patients by stage at pre-
sentation. Further studies are warrant to support this ob-
servation.
In contrast to Romano’s article [4], the ALC/AMC-DX
was found to be an independent of the int-PET to predict
PFS and TTP. A difference between Romano’s article
and this study is that in Romano’s study only 9% (11/115)
cHL patients presented with an ALC/AMC-DX < 1.1 and
in our study it was 21%, suggesting as Romano stated
that in difference series, a different cut-off value should
be calculated. This is well-documented by the paper of
Koh et al. [3] where they used a cut-off of 2.9, instead of
1.1 to confirm that the ALC/AMC-DX was an inde-
pendent predictor of survival in cHL. It is important to
point out that even though statistical methods are useful
to identify cut-off values of new prognostic bio-markers,
new bio-markers need to be biologically sound to help us
understand and improve clinical outcomes. This current
study in addition to our previous publication [1], the
studies by Koh [3] and Romano [4] continue to add more
information to understand the role of the ALC/AMC-DX
on survival in cHL.
To minimize the inherent biases of a retrospective
study, the following steps were taken. With regards to
selection bias, we included only patients with cHL and
excluded patients with nodular lymphocyte predominant
Hodgkin’s lymphoma who are considered to have a dif-
ferent disease entity. We excluded patients treated up-
front with palliative care or radiation alone, as chemo-
therapy and combination chemotherapy and radiation are
considered the current standard of care for cHL patients.
All patients were treated with the same chemotherapy
regimen: ABVD. Patients who were positive for human
immunodeficiency virus and concomitant autoimmune
disease treated with immunosuppressive therapies were
also excluded as these diseases and treatment directly in-
fluence ALC and AMC values. A strength of the study is
the long-term follow-up of a well-defined group of pa-
tients with cHL. Secondly, the ALC/AMC-DX is simple,
easily determined clinical biomarker that can be used to
assess clinical outcomes in cHL in conjunction with the
routine use of int-PET.
5. Conclusion
The combination of ALC/AMC-DX and int-PET as rep-
resentative markers of host immunity, tumor microenvi-
ronment, and tumor burden can stratified clinical out-
comes in cHL and further studies are warranted to con-
firm our findings.
REFERENCES
[1] L. F. Porrata, K. Ristow, J. P. Colgan, T. M. Habermann,
T. E. Witzig, D. J. Inwards, et al., “Peripheral Blood Lym-
phocyte/Monocyte Ratio at Diagnosis and Survival in
Classical Hodgkin’s Lymphoma,” Hematologica, Vol. 97,
No 2, 2012, pp. 262-269.
doi:10.3324/haematol.2011.050138
[2] Y. W. Koh, H. J. Kang, C. Park, D. H. Yoon, S. Kim, et
al., “The Ratio of the Absolute Lymphocyte Count to the
Absolute Monocyte Count Is Associated with Prognosis
in Hodgkin’s Lymphoma: Correlation with Tumor Asso-
ciated Macrophages,” Oncologist, Vol. 17, No. 6, 2012,
pp. 871-880.
[3] T. Terasawa, J. Lau, S. Bardet, O. Couturier, T. Hotta, M.
Hutchings, et al., “Fluorine-18-Fluorodeoxyglucose Posi-
tron Emission Tomography for Interim Response Assess-
ment of Advanced-Stage Hodgkin’s Lymphoma and Dif-
fuse Large B-Cell Lymphoma: A Systemic Review,” Jour-
nal of Clinical Oncology Vol. 27, No. 11, 2009, pp. 1906-
1914. doi:10.1200/JCO.2008.16.0861
[4] A. Romano, C. Vetro, D. Donnarumma, S. Forte, M. Ip-
polito and F. Di Raimondo, “Early Interim 2-(1)Fluoro-2-
deoxy-D-glucose Positron Emission Tomography Is Prog-
nostically Superior to Peripheral Blood Lymphocyte/Mo-
nocyte Ratio at Diagnosis in Classical Hodgkin’s Lym-
phoma,” Hae matologica, Vol. 97, No. 6, 2012, pp. e22-e23.
doi:10.3324/haematol.2012.064576
[5] C. J. Cox, T. M. Habermann, B. A. Payne, G. G. Klee,
and R. V. Pierre. “Evaluation of the Coulter Counter
Model S-Puls IV,” American Journal of Clinical Pathol-
ogy, Vol. 84, No. 3, 1985, pp. 297-306.
[6] D. Hasenclever, V. Diehl, J. O. Armitage, D. Assouline,
M. Bjorkholm, E. Brusamolino, et al., “A Prognostic
Score for Advanced Hodgkin’s Disease,” New England
Journal of Medicine, Vol. 339, No. 21, 1998, pp. 1506-
1514. doi:10.1056/NEJM199811193392104
[7] B. D. Chelson, B. Pfistner, M. E. Juweid, R. D. Gascoyne,

Absolute Lymphocyte/Monocyte Ratio at Diagnosis and Interim Positron-Emission Tomography
Predict Survival in Classical Hodgkin Lymphoma
459
L. Specht, S. J. Horning, et al., “Revised Response Crite-
ria for Malignant Lymphoma,” Journal of Clinical On-
cology, Vol. 25, No. 5, 2007, pp. 579-586.
[8] E. Kaplan and P. Meier, “Nonparametric Estimation from
Incomplete Observations,” Journal of the American Sta-
tistical Association Vol. 53, No. 282, 1958, pp. 457-481.
doi:10.1080/01621459.1958.10501452
[9] D. R. Cox, “Regression Models and Life-Tables,” Jour-
nal of the Royal Statistical Society series B, Vol. 34, No.
2, 1972, pp. 187-202.