Absolute Lymphocyte/Monocyte Ratio at Diagnosis and Interim Positron-Emission Tomography Predict Survival in Classical Hodgkin Lymphoma

doi:10.4236/jct.2013.43A055

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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.

Email: *[email protected]

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)

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.

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