Journal of Cancer Therapy, 2013, 4, 1298-1305
http://dx.doi.org/10.4236/jct.2013.48153 Published Online October 2013 (http://www.scirp.org/journal/jct)
Day 100 Absolute Monocyte/Lymphocyte Prognostic Score
and Survival Post Autologous Peripheral Blood
Hematopoietic Stem Cell Transplantation in
Diffuse Large B-Cell Lymphoma*
Ana I. Velazquez, David J. Inwards, Stephen M. Ansell, Ivana N. Micallef, Patrick B. Johnston,
William J. Hogan, Svetomir N. Markovic, Luis F. Porrata#
Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, USA.
Email: #porrata.luis@mayo.edu
Received September 4th, 2013; revised October 2nd, 2013; accepted October 9th, 2013
Copyright © 2013 Ana I. Velazquez et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
Day 100 prognostic factors post-autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT) to
predict clinical outcomes in diffuse large B-cell lymphoma (DLBCL) patients have not been studied. Thus, we retro-
spectively examined if day 100 absolute monocyte/lymphocyte prognostic score (AMLPS-100) affects clinical out-
comes by landmark analysis from day 100 post-APBHSCT in DLBCL. Only DLBCL patients in complete remission at
day 100 post-APBHSCT were evaluated. From 2000 to 2007, 134 consecutive DLBCL patients are qualified for the
study. Patients with a day 100 absolute monocyte count (AMC-100) 630 cells/μL and day 100 absolute lymphocyte
count (ALC-100) 1000 cells/μL experienced inferior overall survival (OS) and progression free survival (PFS). On
multivariate analysis, the AMC-100 and ALC-100 remained independent predictors of OS and PFS. Combining both
values into the AMLPS-100, the 5-year OS rates for low, intermediate, and high AMLPS-100 risk groups were 94%
(95% CI, 83.0% - 98.1%), 70% (95% CI, 58.6% - 80.1%), and 13% (95% CI, 3.4% - 40.5%), respectively; and the
5-year PFS rates were 87% (95% CI, 74.0% - 94.1%), 68% (95% CI, 56.0% - 77.8%), and 13% (95% CI, 3.4% -
40.5%), respectively. The AMLPS-100 is a simple biomarker score that can stratify clinical outcomes from day 100
post-APBHSCT in DLBCL patients.
Keywords: Monocyte/Lymphocyte Prognostic Score; Diffuse Large B-Cell Lymphoma; Survival; Autologous
Peripheral Blood Hematopoietic Stem Cell Transplantation
1. Introduction
Day 100 visit after stem cell transplantation is the current
standard first follow-up visit to assess treatment response.
Day 100 absolute lymphocyte count (ALC-100) [1], day
100 absolute monocyte count (AMC-100) [1], day 100
platelet count [2], graft versus host disease [3], and day
100 full donor chimerism [4] are day 100 prognostic fac-
tors related to clinical outcomes in allogeneic stem cell
transplantation. In autologous peripheral blood hemato-
poietic stem cell transplantation (APBHSCT), multiple
myeloma documented minimal residual disease at day
100 was associated with inferior survival. Nevertheless,
prognostic factors to assess prognosis for diffuse large
B-cell lymphoma (DLBCL) patients achieving a com-
plete remission at day 100 post-APBHSCT have not been
evaluated. We previously reported that the absolute lym-
phocyte count (ALC) and absolute monocyte count (AMC)
at diagnosis are independent predictors of overall survi-
val (OS) and progression-free survival (PFS) in DLBCL
[5]. The combination of both biomarkers into the AMC/
ALC prognostic score (AMLPS) stratifies patients into
three risk groups: low—(AMC < 630 cells/μL and ALC
> 1000 cells/μL), intermediate—(AMC 630 cells/μL or
ALC 1000 cells/μL) and high-risk (AMC 630 cells/
*Financial Disclosure Statement: This publication was supported in
p
art by Mayo CTSA Grant Number UL1TR000135 from the National
Center for Advancing Translational Sciences. Its contents are solely
the responsibility of the authors and do not necessarily represent the
official view of NIH.
Conflict of Interest: The authors declare no conflict of interest.
#Corresponding author.
Copyright © 2013 SciRes. JCT
Day 100 Absolute Monocyte/Lymphocyte Prognostic Score and Survival Post Autologous Peripheral
Blood Hematopoietic Stem Cell Transplantation in Diffuse Large B-Cell Lymphoma
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μL and ALC 1000 cells/μL) [5]. The AMLPS has been
recently validated in several independent studies [6,7]
confirming its utility as an assessment tool of prognosis
in DLBCL. Post-transplant immunologic reconstitution,
particularly ALC recovery (ALC 500 cells/µL) at day
15, has also been associated with prolonged PFS and OS
in multiple hematological malignancies [8-19] and solid
tumors [20-22].
However, recent reports suggest that the survival
benet obtained from early lymphocyte recovery post-
stem cell transplant in DLBCL patients could be lost with
long-term follow-up [10]. Therefore, the aim of this
study was to evaluate if day 100 AMLPS (AMLPS-100)
affects survival for DLBCL patients in complete remis-
sion at day 100 post-APBHSCT. The value of AMLPS-
100 was also evaluated as a tool to identify high-risk
patients for post-APBHSCT relapse that is simple and
could be easily implemented in clinical practice.
2. Materials and Methods
2.1. Patient Population
DLBCL patients achieving complete remission at day
100 post-APBHSCT at Mayo Clinic, Rochester, MN
between 2000 and 2007 were considered for this study.
Patients transplanted with bone marrow or combined
bone marrow and peripheral blood stem cells and pa-
tients with evidence of relapse or progression at day 100
post-APBHSCT were excluded. A total of 134 consecu-
tive DLBCL patients in complete remission at day 100
post-APBHSCT qualified for the study. No patient re-
fused authorization to use their medical records for re-
search and none were lost to follow-up. Approval for the
retrospective review of these patients’ records was ob-
tained from the Mayo Clinic Institutional Review Board
and the research was conducted in accordance with US
federal regulations and the Declaration of Helsinki.
2.2. End Points
The primary end point of the study was to assess the im-
pact of AMLPS-100 on OS and PFS by landmark analy-
sis from day 100 in DLBCL patients treated with
APBHSCT. The AMC-100, ALC-100, and AMLPS-100
were obtained from a standard day 100 complete blood
cell count (CBC). The secondary end point was to evalu-
ate if the AMLPS-100 could stratify DLBCL patients
into low-, intermediate- and high-risk groups for OS and
PFS post-APBHSCT.
2.3. Conditioning Regimen
All patients received carmustine (BCNU) 300mg/m2 on
day-6; etoposide 100mg/m2 twice a day on days-5, -4, -3,
and -2; cytarabine 100 mg/m2 twice a day on days-5, -4,
-3, -2; and melphalan 140mg/m2 on day-1 (BEAM).
2.4. Prognostic Factors
Prognostic factors evaluated include: age at day 100
(Age-100), ALC-100, AMC-100, absolute neutrophil
count at day 100 (ANC-100), gender, International Prog-
nostic Index (IPI) at diagnosis, infused CD34+ cell dose,
lactate dehydrogenase at day 100 (LDH-100), hemog-
lobin at day 100 (Hgb-100), platelets at day 100 (Plts-
100), day 15 absolute lymphocyte count post-APBHSCT
(ALC-15), and white blood cell count at day 100 (WBC-
100).
2.5. Response and Survival
Response criteria were based on the guidelines from the
International Harmonization Project for Malignant Lym-
phoma [23]. OS was measured from day 100 to the date
of death, or last follow-up. PFS was defined as the time
from day 100 to the time of progression, relapse, death,
or last follow-up, whichever occurred first.
2.6. Statistical Analysis
OS and PFS were analyzed using the approach of Kap-
lan-Meier [24]. Differences between the survival curves
were tested for statistical significance using the 2-tailed
log-rank test. The Cox proportional hazard model was
used for the univariate and multivariate analysis to evalu-
ate the impact of the variables listed under the prognostic
factors section for OS and PFS times [25]. The choice of
the cut-off values for ALC-100 and AMC-100 was based
on our previous AMLPS publication [5]. χ2 analysis was
used to determine relationships between categorical
variables. The Wilcoxon-rank test was used to determine
associations between continuous variables and categories,
and Spearman correlation coefficients were used to eva-
luate associations for continuous variables. All two-
sided p-values < 0.05 were determined to be statistically
significant.
3. Results
3.1. Patients’ Characteristics
For this cohort of 134 DLBCL patients, the median age
at day 100 post-APBHSCT was 57.5 years (range: 23 -
77 years). Sixty-three percent of the patients were males,
while 37% were females. The distribution of the patients’
baseline characteristics at day 100 is included in Table 1.
The median follow-up period from day 100 post-
APBHSCT for the cohort was 5.5 years (range: 0.1 - 12.7
years) and for living patients (N = 93) was 6.9 years
(range: 2.5 - 12.7 years). Twenty-seven patients died
Copyright © 2013 SciRes. JCT
Day 100 Absolute Monocyte/Lymphocyte Prognostic Score and Survival Post Autologous Peripheral
Blood Hematopoietic Stem Cell Transplantation in Diffuse Large B-Cell Lymphoma
Copyright © 2013 SciRes. JCT
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Table 1. Baseline patients’ characteristics at day 100 (N = 134).
Characteristics N (%) Median Range
Gender
Male 84 (63)
Female 50 (37)
Age-100, years 134 (100) 57.5 (23 - 77)
CD34+ 134 (100) 4.43 (2.05 - 14.85)
ALC-15, ×109/L 134 (100) 0.575 (0.02 - 2.4)
AMC-100, ×109/L 134 (100) 0.49 (0.08 - 1.8)
ALC-100, ×109/L 134 (100) 1.045 (0.17 - 5.6)
ANC-100, ×109/L 134 (100) 2.455 (0.22 - 7.8)
WBC-100, ×109/L 134 (100) 4.4 (1.1 - 10.9)
Hgb-100, g/L 134 (100) 11.75 (7.5 - 15.8)
Plts-100, ×109/L 134 (100) 152.5 (17 - 403)
LDH-100, U/L 134 (100) 167.5 (111 - 383)
IPI
0 13 (9.7)
1 44 (32.8)
2 52 (38.8)
3 21 (15.7)
4 4 (3)
AMLPS-100
Low risk 50 (37.3)
Intermediate risk 69 (51.5)
High risk 15 (11.2)
Abbreviations: ALC = absolute lymphocyte count; AMC = absolute monocyte count; ANC = absolute neutrophil count; WBC = white blood cell count; Hgb =
hemoglobin; Plts = platelets; LDH = lactate dehydrogenase; IPI = International Prognostic Index; AMLPS = AMC/ALC Prognostic Score.
secondary to relapsed DLBCL. Fourteen patients died of
causes not related to DLBCL: 3 patients died of acute
respiratory distress syndrome; 3 patients of myelodys-
plastic syndrome; 2 patients of acute myelogenous leu-
kemia; 2 patients of myocardial infarction; 2 patients of
suicide; 1 patient of a motor vehicle accident; and 1 pa-
tient of sepsis.
3.2. AMC-100, ALC-100, and Survival
To determine if AMC-100 and ALC-100 affect survival,
we evaluated by univariate analysis both variables as
continuous predictors of OS and PFS. As continuous
variables both, AMC-100 and ALC-100, predicted OS
[Hazard ratio (HR) = 7.16, p < 0.0001 and HR = 0.42, p
< 0.009, respectively] and PFS [HR = 5.06, p < 0.0005
and HR = 0.44, p < 0.005, respectively] (Table 2).
AMC-100 and ALC-100 were dichotomized using cut-
off values previously published [AMC: < 630 cells/μL vs.
630 cells/μL; ALC: 1000 cells/μL vs. > 1000
cells/μL] [5]. An elevated AMC-100, defined as 630
cells/μL, was associated with inferior OS and PFS on
univariate analysis [OS: HR = 2.46, (95% CI, 1.32 -
4.55), p < 0.005; PFS:HR = 1.75, (95% CI, 0.99 - 3.03),
p < 0.05]. An ALC-100 1000 cells/μL was associated
with inferior OS and PFS [OS: HR = 4.85, (95% CI, 2.46
- 10.43), p < 0.0001; PFS: HR = 3.41, (95% CI, 1.93 -
6.25), p < 0.0001]. Figures 1(a) and (b) show superior
OS and PFS based on AMC-100 < 630 cells/μL versus
AMC-100 630 cells/μL [median OS = not reached vs.
7.3 years, 5-year OS rates of 80%, (95% CI 70.4% -
87.1%) vs. 55%, (95% CI, 40.1% - 69.9%), p < 0.007,
respectively; and median PFS = 10.9 years vs. 7.3 years,
5-year PFS rates of 75%, (95% CI 64.7% - 82.6%), vs.
55%, (95% CI, 40.1% - 69.9%), p < 0.04, respectively].
Figures 1(c) and (d) show superior OS and PFS based on
Day 100 Absolute Monocyte/Lymphocyte Prognostic Score and Survival Post Autologous Peripheral
Blood Hematopoietic Stem Cell Transplantation in Diffuse Large B-Cell Lymphoma
1301
Table 2. Univariate analysis for overall survival and progression-free survival.
Overall survival Progression-free survival
Prognostic factors
HR (95% CI) p-value HR (95% CI) p-value
Gender <0.0227
Male 2.19 (1.11 - 4.70) 1.76 (0.99 - 3.32)
Female 0.46 (0.21 - 0.90) 0.57 (0.30 - 1.01)
0.0552
Age-100, years (continuous variable) 1.05 (1.02 - 1.08) <0.0003 1.04 (1.02 - 1.07) <0.0002
Age at day 100, 60 years 2.59 (1.38 - 5.08) <0.0029 2.54 (1.46 - 4.56) <0.0009
CD34+ 0.84 (0.69 - 0.99) <0.0404 0.87 (0.74 - 1.01) 0.0631
IPI, 2 1.60 (0.85 - 3.13) 0.1508 1.62 (0.92 - 2.93) 0.0940
ALC-15, ×109/L 0.20 (0.07 - 0.52) <0.0005 0.37 (0.15 - 0.80) <0.0104
AMC-100, ×109/L (continuous variable) 7.11 (2.86 - 16.08) <0.0001 5.06 (2.12 - 11.00) <0.0005
AMC-100 630/μL 2.46 (1.32 - 4.55) <0.0048 1.75 (0.99 - 3.03) 0.0533
ALC-100, ×109/L (continuous variable) 0.42 (0.20 - 0.82) <0.0094 0.44 (0.22 - 0.79) <0.0049
ALC-100 1000/μL 4.85 (2.46 - 10.43) <0.0001 3.41 (1.93 - 6.25) <0.0001
ANC-100 ×109/L 1.13 (0.91 - 1.36) 0.2635 1.11 (0.92 - 1.32) 0.2814
WBC-100, ×109/L 1.05 (0.89 - 1.22) 0.5687 1.04 (0.89 - 1.19) 0.6376
Hgb-100, g/L 0.71 (0.59 - 0.85) <0.0002 0.78 (0.67 - 0.92) <0.0026
Plts-100, ×109/L 1.00 (0.994 - 1.001) 0.2590 0.99 (0.99 - 1.00) 0.6292
LDH-100, U/L 1.00 (1.00 - 1.01) 0.2274 1.00 (0.99 - 1.01) 0.3386
Abbreviations: IPI = International Prognostic Index; ALC = absolute lymphocyte count; AMC = absolute monocyte count; ANC = absolute neutrophil count;
WBC = white blood cell count; Hgb = hemoglobin; Plts = platelets; LDH = lactate dehydrogenase.
(a) (b)
(c) (d)
Figure 1. (a) Kaplan-Meier estimates of overall survival from day 100 post-APBHSCT based on day 100 absolute monocyte
count (AMC-100); (b) Kaplan-Meier estimates of progression-free survival from day 100 post-APBHSCT based on day 100
absolute monocyte count (AMC-100); (c) Kaplan-Meier estimates of overall survival from day 100 post-APBHSCT based on
day 100 absolute lymphocyte count (ALC-100); and (d) Kaplan-Meier estimates of progression-free survival from day 100
post-APBHSCT based on day 100 absolute lymphocyte count (ALC-100).
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Day 100 Absolute Monocyte/Lymphocyte Prognostic Score and Survival Post Autologous Peripheral
Blood Hematopoietic Stem Cell Transplantation in Diffuse Large B-Cell Lymphoma
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ALC-100 > 1000 cells/μL versus ALC-100 1000 cells/
μL [median OS = not reached vs. 5.1 years, 5-year OS
rates of 89%, (95% CI, 80.2% - 94.6%), vs. 49%, (95%
CI, 36.1% - 61.7%), p < 0.0001, respectively; and me-
dian PFS = not reached vs. 4.8 years, 5-year PFS rates of
85%, (95% CI = 74.9% - 91.5%) vs. 46%, (95% CI,
33.6% - 58.9%), p < 0.0001, respectively].
3.3. Univariate and Multivariate Analysis
Gender, age-100 (continuous and dichotomized), CD34+,
IPI, ALC-15, ALC-100 (continuous and dichotomized),
AMC-100 (continuous and dichotomized), and Hgb-100
were identified as predictors for OS and PFS in the uni-
variate analysis (Table 2). In the multivariate analysis,
CD34+ and ALC-15 continue to be independent predic-
tors of OS and PFS post-APBHSCT; age dichotomized
as < or 60 years was associated with PFS. Both
AMC-100 630 cells/μL and ALC-100 1000 cells/μL
remained as independent predictors of OS after adjusting
for several variables on multivariate analysis, with haz-
ard ratios of 3.83 and 5.46 respectively (p < 0.0002; p <
0.0001); both day 100 variables were independent pre-
dictors of PFS (Table 3).
3.4. Day 100 AMLPS (AMLPS-100)
By univariate and multivariate analysis, the ALC-100
and AMC-100 were independent predictors for OS and
PFS post-APBHSCT. Thus, we combinedALC-100 and
AMC-100 into day 100 AMC/ALC prognostic score
(AMLPS-100), using the same cut-off values from our
previous publication of the AMLPS at diagnosis in
DLBCL [5], to develop a simple scoring system that can
be used to stratify by risk patients with DLBCL that are
in complete disease remission at day 100 post-APBHSCT.
According to the AMLPS-100, 37.3% (N = 50) of the
patients were considered low risk (AMC < 630 cells/μL
and ALC > 1000 cells/μL), 51.5% (N = 69) intermediate
risk (AMC 630 cells/μL or ALC 1000 cells/μL), and
11.2% (N = 15) high risk (AMC 630 cells/μL and ALC
1000 cells/μL) (Table 4). Among the groups significant
differences were seen in ALC-100, AMC-100, ANC-100,
and HgB-100. Patients with a low-risk AMLPS-100 ex-
perienced significantly superior OS and PFS compared to
the other groups, with a 5-year OS rate of 94% (95% CI,
83.0% - 98.1%); median not reached; p < 0.0001 and a
5-year PFS rate of 87% (95% CI, 74.0% - 94.1%); me-
dian not reached; p < 0.0001 (Figures 2(a) and (b)). The
estimated 5-year OS among intermediate-risk patients
was 70% (95% CI, 58.6% - 80.1%); median not reached
(Figure 2(a)) and the 5-year PFS was 68% (95% CI,
56.0% - 77.8%) with a median PFS of 10.9 years (Figure
2(b)). The AMLPS-100 identified a group of high-risk
patients with median OS of 2.18 years and an estimated
5-year OS of 13% (95% CI, 3.4% - 40.5%) (Figure 2(a)).
Similarly, the median PFS for high-risk patients was 1
year with an estimated 5-year PFS rate of 13% (95% CI,
3.4% - 40.5%) (Figure 2(b)).
4. Discussion
Currently, there are no studies available to advise
DLBCL patients in complete remission at day 100 post-
APBHSCT of their long-term prognosis starting at day
100 post-APBHSCT. We previously published the
AMLPS at diagnosis for DLBCL stratifies patients into
three risk groups in regard to clinical outcomes. This
AMLPS has been validated as an independent prognostic
indicator in DLBCL patients by other independent
groups [6,7]. Hence, we sought to evaluate if the AMLPS-
Table 3. Multivariate analysis for overall survival and progression-free survival.
Overall survival Progression-free survival
Prognostic factors
HR (95% CI) p-value HR (95% CI) p-value
Gender 0.4792 0.4949
Male 1.32 (0.62 - 2.96) 1.24 (0.67 - 2.40)
Female 0.76 (0.34 - 1.60) 0.80 (0.42 - 1.49)
Age-100, 60 years 1.57 (0.77 - 3.34) 0.2213 2.16 (1.17 - 4.09) <0.0142
CD34+ 0.83 (0.70 - 0.97) <0.0175 0.89 (0.76 - 1.01) 0.0751
IPI, 2 1.88 (0.95 - 3.88) 0.0720 1.90 (1.05 - 3.57) <0.0341
ALC-15, ×109/L 0.28 (0.09 - 0.074) <0.0094 0.54 (0.22 - 1.22) 0.1393
Hgb-100, g/L 3.83 (1.89 - 7.85) <0.0002 2.23 (1.19 - 4.15) <0.0132
AMC-100, 630/μL 3.83 (1.32 - 5.28) <0.0002 4.30 (2.31 - 8.31) <0.0001
ALC-100, 1000/μL 5.46 (2.99 - 14.10) <0.0001 5.04 (2.70 - 9.80) <0.0001
Abbreviations: IPI = International Prognostic Index; ALC = absolute lymphocyte count; AMC = absolute monocyte count; Hgb = hemoglobin.
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Day 100 Absolute Monocyte/Lymphocyte Prognostic Score and Survival Post Autologous Peripheral
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Table 4. Baseline patients’ characteristics based on AMLPS-100.
Characteristics Low Risk (N = 50) Intermediate Risk (N = 69)High Risk (N = 15) p-value
Gender
Male 30 (60%) 43 (62%) 11 (73%)
Female 20 (40%) 26 (38%) 4 (27%)
0.6424
Age-100, years 58.5 (24 - 75) 56(23-76) 62 (41 - 77) 0.2190
CD34+ 4.47 (2.05 - 8.23) 4.41 (2.11 - 14.85) 3.82 (2.22 - 9.95) 0.9875
ALC-15, ×109/L 0.68 (0.03 - 2.4) 0.56 (0.02 - 1.89) 0.47 (0.14 - 1.79) 0.2133
AMC-100, ×109/L 0.43 (0.08 - 0.61) 0.50 (0.08 - 1.80) 1.00 (0.63 - 1.65) <0.0001
ALC-100, ×109/L 1.26 (1.01 - 3.06) 0.91(0.17 - 5.60) 0.71 (0.20 - 0.92) <0.0001
ANC-100, ×109/L 2.30 (0.27 - 5.25) 2.59(0.28 - 7.80) 3.27 (0.22 - 6.83) <0.0462
WBC-100, ×109/L 4.4 (1.9 - 9.3) 4 (1.1 - 10.8) 4.6 (1.9 - 10.9) 0.3008
Hemoglobin at day 100, g/L 12.5 (7.9 - 15.8) 11.3 (7.5 - 14.7) 11.8 (8.1 - 13.8) <0.0027
Platelets at day 100, ×109/L 164 (23 - 373) 139 (17 - 403) 195 (36 - 299) 0.0939
LDH-100, U/L 170 (117 - 286) 166 (111 - 383) 162 (130 - 255) 0.9301
IPI
0 4 (8%) 9 (13%) 0 (0%)
1 16 (32%) 26 (36%) 3 (20%)
2 23 (46%) 22 (32%) 7 (47%)
3 6 (12%) 10 (15%) 5 (33%)
4 1 (2%) 3 (4%) 0 (0%)
0.2883
Abbreviations: ALC = absolute lymphocyte count; AMC = absolute monocyte count; ANC = absolute neutrophil count; WBC = white blood cell count; Hgb =
hemoglobin; Plts = platelets; LDH = lactate dehydrogenase; IPI = International Prognostic Index.
(a) (b)
Figure 2. Kaplan-Meier estimates of overall (a) and progression free (b) survival for the entire cohort of patients stratified by
the AMC/ALC prognostic score at day 100 (AMLPS-100, stratifying patients into low risk (ALC-100 > 1000 cells/μL and
AMC-100 < 630 cells/μL); intermediate-risk (ALC-100 1000 cells/μL or AMC-100 630 cells/μL); and high-risk (ALC-100
1000 cells/μL and AMC-100 630 cells/μL).
100 retains its ability to predict clinical outcomes at day
100 post-APBHSCT making it a risk-assessing tool that
could be used during follow-up of DLBCL patients in
complete remission.
To support the hypothesis that the biomarker AMLPS-
100 affects survival in DLBCL patients, it was necessary
to demonstrate that both ALC-100 and AMC-100 were
associated with clinical outcomes in DLBCL patients in
complete remission at day 100 post-APBHSCT. We de-
termined that DLBCL patients presenting with ALC-100
> 1000 cells/μL experienced significantly superior OS
and PFS. Similarly, DLBCL patients with an AMC-100
< 630 cells/μL presented superior OS and PFS from day
100 post-APBHSCT.
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Day 100 Absolute Monocyte/Lymphocyte Prognostic Score and Survival Post Autologous Peripheral
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Since both the ALC-100 and AMC-100 were inde-
pendent predictors for OS and PFS, we combined them
into AMLPS-100. The AMLPS-100 was able to stratify
patients into low-, intermediate-, and high-risk groups for
OS and PFS post-APBHSCT.
To minimize the inherent biases of a retrospective
study, the following steps were taken. With regards to
selection bias, we only included DLBCL patients that
underwent APBHSCT. Patients infused with peripheral
blood as well as bone marrow harvested stem cells were
excluded. All patients were treated with the same condi-
tioning regimen. All patients were required to be in com-
plete remission at day 100 for the landmark analysis.
With regards to confounding factors, our study included
currently known prognostic factors, such as the IPI; in
addition, we included Age-100, Hgb-100, ANC-100, LDH-
100, WBC-100, and Plts-100, all of which have been re-
ported as prognostic factors at day 100 post-allogeneic
stem cell transplantation [1-4].
On the other hand, strengths of this study include the
long follow-up period of a well-defined group of DLBCL
patients in complete remission at day 100 post-
APBHSCT, with a median follow-up from day 100 post-
APBHSCT for the cohort of 5.5 years and 6.9 years for
living patients. Secondly, AMLPS-100 combines clinical
biomarkers for the host immunity (i.e., ALC) [5] and
tumor microenvironment (i.e., AMC) [26,27]. Thirdly,
the AMLPS-100 is a simple biomarker score obtained
from the day 100 CBC post-APBHSCT that can be used
to assess clinical outcomes in DLBCL patients in com-
plete remission at day 100 post-APBHSCT, whereas
other prognostic techniques such as gene-expression pro-
filing required fresh frozen tissue samples, limiting its
use in complete remission DLBCL patients at day 100
post-APBHSCT. Further studies are warranted to vali-
date the AMLPS-100.
5. Acknowledgements
This publication was supported in part by Mayo CTSA
Grant Number UL1TR000135 from the National Center
for Advancing Translational Sciences. Its contents are
solely the responsibility of the authors and do not neces-
sarily represent the official view of NIH.
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