Su et al.

BMC Cancer (2015) 15:429

DOI 10.1186/s12885-015-1442-3

RESEARCH ARTICLE
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Leucopenia and treatment efficacy in advanced

nasopharyngeal carcinoma
1

Zhen Su , Yan-Ping Mao , Pu-Yun OuYang , Jie Tang , Xiao-Wen Lan and Fang-Yun Xie

1,2*

Abstract
Background: Leucopenia or neutropenia during chemotherapy predicts better survival in several cancers. We
aimed to assess whether leucopenia could be a biological measure of treatment and a marker of efficacy in
advanced nasopharyngeal carcinoma (ANPC).
Methods: We retrospectively analyzed 3826 patients with ANPC who received chemoradiotherapy. Leucopenia
was categorised on the basis of worst grade during treatment according to the National Cancer Institute Common
Toxicity Criteria version 4.0: no leucopenia (grade 0), mild leucopenia (grade 12), and severe leucopenia (grade
34). Associations between leucopenia and survival were estimated by Cox proportional hazards model.
Results: Of the 3826 patients, 2511 (65.6 %) developed mild leucopenia (grade 12) and 807 (21.1 %) developed
severe leucopenia (grade 34) during treatment; 508 (13.3 %) did not. A multivariate Cox model that included
leucopenia determined that the hazard ratios (HR) of death for patients with mild and severe leucopenia were 0.69
[95 % confidence interval (95 %CI) 0.56-0.85, p < 0.001] and 0.75 (95 %CI 0.59-0.95, p = 0.019), respectively; the HR
of distant metastasis for patients with mild and severe leucopenia were 0.77 (95 %CI 0.61-0.96, p = 0.023) and
0.99 (95 %CI 0.77-1.29, p = 0.995), respectively. Leucopenia had no effect on locoregional relapse.
Conclusions: Our results indicate that mild leucopenia during chemoradiotherapy is associated with improved
overall survival and distant metastasisfree survival in ANPC. Mild leucopenia may indicate appropriate dosage of
chemotherapy. We can identify the patients who may benefit from chemotherapy if they experienced leucopenia
during the treatment. Prospective trials are required to assess whether dosing adjustments based on leucopenia
may improve chemotherapy efficacy.
Keywords: Leucopenia, Advanced nasopharyngeal carcinoma, Chemoradiotherapy, Survival, Treatment efficacy
Background
Nasopharyngeal carcinoma (NPC) is a distinct type of
head and neck cancer. The incidence rate is as high as
2030 per 100,000 populations in endemic areas of
southern China and Southeast Asia [13]. Radiotherapy
(RT) is the primary treatment, plus chemotherapy when
needed according to clinical stage. With the development of diagnostic imaging, chemotherapy regimens,
targeted drugs, and radiotherapeutic techniques, especially the application of IMRT (Intensity Modulated
* Correspondence: [email protected]

Equal contributors
1
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in
South China, Collaborative Innovation Center for Cancer Medicine,
Guangzhou 510060, China
2
Department of Radiation Oncology, Sun Yat-sen University Cancer Center;
State Key Laboratory of Oncology in South China; Collaborative Innovation
Center for Cancer Medicine, Guangzhou 510060, China

Radiation Therapy), survival of NPC has improved significantly [46]. However, 1020 % of patients with advanced NPC (ANPC) develop distant metastasis after
radical chemoradiotherapy, rendering distant metastases
the main reason for treatment failure. To reduce the occurrence
of distant metastasis, different timings of
chemotherapy is recommended for ANPC according to
NCCN (National Comprehensive Cancer Network)
guidelines [7]. In 2014 version of NCCN guidelines , the
categories of evidence for induction or adjuvant chemotherapy of NPC has changed [7]. Category of induction
chemotherapy of NPC changed from category 2A to category 3. Category of adjuvant chemotherapy cisplatin +
RT followed by cisplatin/5-FU changed from category 1
to category 2A and cisplatin + RT followed by carboplatin/5-FU changed from category 2A to category 2B.

2015 Su et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain
Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article,
unless otherwise stated.

Su et al. BMC Cancer (2015) 15:429

Bone marrow suppression is a common adverse reaction of cytotoxic drugs and could be a biological measure of drug activity and might predict treatment efficacy
[8, 9]. Leucopenia or neutropenia during treatment is a
common phenomenon of bone marrow suppression.
Some studies reported that leucopenia or neutropenia is
a prognostic factor predicting better clinical outcome in
several solid tumors, e.g., breast cancer [1012], colorectal cancer [13, 14], advanced gastric cancer [1517], lung
cancer [1820], and Hodgkins lymphoma [21]. Others
have reported different results [22, 23]. However, the
pre- dictive (ie, estimation of the chance of benefit from
chemotherapy) or prognostic
(ie, estimation of the
chance of survival) role of leucopenia in advanced
nasopharyngeal carcinoma have not been established.
We aimed to investigate the association between
leucopenia during treatment and survival of ANPC and
to provide evidences, through rigorous statistical analysis
of a large series of subjects with ANPC, of the utility of
leukocyte count as a surrogate marker of drug efficacy.

Methods
Patients and methods

We retrospectively collected 3939 newly diagnosed ANPC

patients
from January 2005 to December
2010
treated in the Nasopharyngeal Carcinoma Department
of Sun Yat-Sen University Cancer Center. 113 paitents
were ex- cluded owing to different reasons, abnormal liver
function, abnormal kidney function, unsatisfactory blood
sugar con- trol and so on. 3826 patients were involved
in the study. The Sun Yat-Sen University Cancer Center
Institutional Review Board (IRB) and ethics committee
reviewed and approved the study. The study was
retrospective. Patient records were anonymized and
de-identified prior to analysis.
Pretreatment evaluation included complete patient history, physical examination, hematology and biochemistry
profiles, nasopharynx and neck magnetic resonance imaging (MRI), chest radiography, abdominal ultrasound,
bone emission computed tomography (ECT), and chest or
abdomen computed tomography (CT) when necessary.
Treatment

The treatment strategy for all patients was based on National Comprehensive Cancer Network Guidelines [24,
25]. All patients were treated with intensity-modulated
RT (IMRT) or conventional RT (CRT) with chemotherapy; the radiation techniques and chemotherapy regimens have been described previously [26, 27].
Laboratory measurements

We performed leukocyte and neutrophil counts for all

patients within two weeks before therapy and at least
once weekly during treatment. The most severe grade of

Page 2 of 8

leucopenia was based on the lowest recorded leukocyte

count for a given patient between the first day of treatment administration and 1 week after the end of treatment, and was graded according to the National Cancer
Institute Common Toxicity Criteria version 4.0. Patients
were classified as having no leucopenia (grade 0), mild
leucopenia (grade 12), and severe leucopenia (grade 34).
Indications for using granulocyte colonystimulating
factor (G-CSF) were not specified; it was generally used
in grade 34 or febrile leucopenia, and was not used
for prophylaxis.
Follow-up

Patients were regularly followed after RT until death or

their last follow-up appointment. Clinic visits were
scheduled every three months in the first three years,
every six months during the fourth to fifth years, and
once a year after the fifth year. Patients underwent physical examination and nasopharyngoscopy on each visit.
Nasopharynx and neck MRI, chest radiography, abdominal ultrasound, and ECT were performed after RT or
according to clinical indications. The follow-up duration
was calculated from the first day of therapy to the day of
death or the day of last examination.
Statistical analysis

We estimated the following endpoints (interval to the

first defining event): overall survival (OS), locoregional
relapsefree survival (LRFS), and distant metastasisfree
survival (DMFS). Survival curves were estimated using
the Kaplan-Meier method and compared using the logrank test. Multivariate analyses were performed using the
Cox proportional hazards model. We used chi-square
tests and KruskalWallis H tests to assess the statistical
significance of associations between categorical variables
and the three groups. All statistical tests were 2-tailed;
p < 0.05 was considered statistically significant. All
tests were conducted using IBM SPSS version 20.0.0
(IBM Corporation, Armonk, NY, USA).

Results
Patient characteristics

Table 1 lists the patient characteristics. We studied 3826

patients (2873 male; 953 female). The median age at diagnosis for male patients was 46 years (range 2084 years);
that for female patients was 44 years (range 2076 years).
CRT and IMRT were administered to 2583 and 1243 patients, respectively. Induction chemotherapy (IC) was administered to 1073 patients, concurrent chemotherapy
(CC) to 1291 patients, IC plus CC (IC + CC) to 1255 patients, and CC plus adjuvant chemotherapy (CC + AC)
to 207 patients. We administered <4 and 4 chemotherapy cycles to 2364 (61.8 %) and 1462 (38.2 %)
patients, respectively. No significant differences were

Table 1 Patient characteristics according to grade of leucopenia

Variable

All

Absent leucopenia

Mild leucopenia

Severe leucopenia

Total

3826

508(13.3)

2511(65.6)

807(21.1)

male

2873(75.1)

421(82.9)

1936(77.1)

516(63.9)

female

953(24.9)

87(17.1)

575(22.9)

291(36.1)

Gender

P value
<0.001

Age(years)

0.105

<45

1982(51.8)

242(47.6)

1325(52.8)

415(51.4)

> = 45

1844(48.2)

266(52.4)

1186(47.2)

392(48.6)

= < 10 10^9/L

3448(90.1)

424(83.5)

2278(90.7)

746(92.4)

>10 10^9/L

378(9.9)

84(16.5)

233(9.3)

61(7.6)

Leukocyte count

<0.001

Pathological type(WHO)

0.692

83(2.2)

11(2.2)

55(2.2)

17(2.1)

II

203(5.3)

23(4.5)

143(5.7)

37(4.6)

III

3540(92.5)

474(93.3)

2313(92.1)

753(93.3)

T-classification

0.720

T1

172(4.5)

22(4.3)

109(4.3)

41(5.1)

T2

272(7.1)

29(5.7)

185(7.4)

58(7.2)

T3

1871(48.9)

271(53.3)

1221(48.6)

379(47.0)

T4

1511(39.5)

186(36.6)

996(39.7)

329(40.8)

N0

517(13.5)

86(16.9)

335(13.3)

96(11.9)

N1

1978(51.7)

252(49.6)

1313(52.3)

413(51.2)

N2

1043(27.3)

133(26.2)

680(27.1)

230(28.5)

N3

288(7.5)

37(7.3)

183(7.3)

68(8.4)

N-classification

0.09

Clinical stage

0.222

III

2094(54.7)

295(58.1)

1369(54.5)

430(53.3)

IV

1732(45.3)

213(41.9)

1142(45.5)

377(46.7)

CRT

2583(67.5)

329(64.8)

1741(69.3)

513(63.6)

IMRT

1243(32.5)

179(35.2)

770(30.7)

294(36.4)

Radiotherapy

0.004

Chemotherapy

<0.001

IC

1073(28.0)

198(39.0)

697(27.8)

178(22.1)

CC

1291(33.7)

202(39.8)

878(35.0)

211(26.1)

IC + CC

1255(32.8)

98(19.3)

804(32.0)

353(43.7)

CC + AC

207(5.4)

10(2.0)

132(5.3)

65(8.1)

NO

3029(79.2)

403(79.3)

2069(82.4)

557(69.0)

YES

797(20.8)

105(20.7)

442(17.6)

250(31.0)

Paclitaxel

<0.001

Chemotherapy cycles

<0.001

<4

2364(61.8)

400(78.7)

1575(62.7)

389(48.2)

>=4

1462(38.2)

108(21.3)

936(37.3)

418(51.8)

Abbreviations: CRT: conventional radiotherapy; IMRT: intensity modulated radiation therapy; IC: Induction chemotherapy; CC: concurrent chemotherapy;
AC: adjuvant chemotherapy; WHO: world health organization

observed for age, T classification, N classification, and

clinical stage. There were significant differences in pretreatment leukocyte count, type of chemotherapy,
chemotherapy cycles, type of RT, sex, and paclitaxel use
(yes or no) in the compared groups (all p < 0.05). Patients who developed leucopenia during treatment had
lower pretreatment leukocyte counts (p < 0.001). More
female patients developed leucopenia (female vs. male,
90.1 % vs. 85.3 %, p < 0.001); patients using paclitaxel
were likely to develop severe leucopenia (31.4 % vs.
18.4 %, p < 0.001).
The median OS was 52.6 months (range 3.07113.0
months); 10.9 % of patients (417/3826) developed locoregional relapse, 16.5 % (633/3826) developed distant metastases, and 19.0 % (727/3826) died. The 5-year OS,
LRFS, and DMFS rates for the entire population were
80.70 %, 87.9 %, and 82.1 %, respectively.
During treatment, 2511 patients (65.6 %) developed
mild leucopenia (grade 12) and 807 patients (21.1 %)

developed severe leucopenia (grade 34); the remaining

508 (13.3 %) did not develop leucopenia.
Survival analyses including leucopenia

Table 2 shows the univariate analysis of the baseline and

clinical characteristics as prognostic factors, including
leucopenia. KaplanMeier curves according to severity of
leucopenia showed that better OS and DMFS were predicted for patients with leucopenia and that leucopenia had
no significant effect on LRFS (Fig. 1). The 5-year OS rate
in patients with no leucopenia, mild leucopenia, and severe
leucopenia
was 75.5 %, 81.9 %, and 80.5 %,
respectively (mild vs no leucopenia, p = 0.001; severe vs
no leucopenia, p = 0.03; mild vs severe, p = 0.314). The 5year DMFS rate in patients with no leucopenia, mild
leucopenia, and severe leucopenia was 79.7 %, 83.7 %,
and 78.9 %, respectively (mild vs. no leucopenia, p =
0.038; severe vs no leucopenia, p = 0.927; mild vs severe, p
= 0.007). The 5-year LRFS rate in patients with no
leucopenia, mild leucopenia, and severe

Table 2 Univariate analysis of survival for patients with ANPC

All population

Cycles <4 population

Cycles > =4 population

OS

DMFS

OS

DMFS

OS

DMFS

HR(95 %CI)

0.70(0.57-0.86)

0.79(0.63-0.98)

0.73(0.57-0.92)

0.87(0.66-1.14)

0.56(0.38-0.86)

0.56(0.37-0.86)

0.001

0.038

0.009

0.309

0.007

0.008

HR(95 %CI)

0.77(0.60-0.97)

1.01(0.78-1.31)

0.86(0.63-1.16)

1.10(0.79-1.54)

0.59(0.38-0.90)

0.73(0.46-1.14)

0.030

0.927

0.320

0.554

0.016

0.166

HR(95%CI)

0.91(0.76-1.09)

0.77(0.64-0.93)

0.85(0.66-1.08)

0.78(0.61-1.02)

0.98(0.75-1.28)

0.77(0.58-1.09)

0.314

0.007

0.191

0.069

0.887

0.058

HR(95 %CI)

0.62(0.51-0.75)

0.69(0.57-0.84)

0.63(0.50-0.79)

0.71(0.55-0.91)

0.61(0.45-0.84)

0.67(0.49-0.2)

<0.001

<0.001

<0.001

0.007

0.002

0.015

HR(95 %CI)

1.84(1.59-2.14)

1.09(0.93-1.27)

1.93(1.59-2.34)

1.14(0.94-1.39)

1.73(1.36-2.19)

1.01(0.77-1.30)

<0.001

0.304

<0.001

0.191

<0.001

0.941

HR(95 %CI)

1.27(1.14-1.40)

1.09(0.99-1.22)

1.27(1.11-1.45)

1.11(0.96-1.27)

1.26(1.07-1.49)

1.08(0.91-1.27)

<0.001

0.092

0.001

0.157

0.007

0.375

HR(95CI)

1.56(1.43-1.70)

1.65(1.50-1.81)

1.70(1.51-1.90)

1.75(1.54-1.97)

1.39(1.21-1.60)

1.52(1.32-1.76)

<0.001

<0.001

<0.001

<0.001

<0.001

<0.001

HR(95 %CI)

0.80(0.68-0.94)

0.91(0.76-1.08)

0.88(0.70-1.10)

1.03(0.82-1.30)

0.69(0.54-0.89)

0.75(0.58-0.97)

0.008

0.273

0.264

0.764

0.005

0.030

Variable
Leucopenia
Mild VS Absent

Severe VS Absent

Mild VS Severe

Gender

Age

T-classification

N-classification

Radiotherapy

Abbreviations: OS: overall survival; DMFS: distant metastasis-free survival; HR: hazard ratio; CI: confidence interval; ANPC: advanced nasopharyngeal carcinoma

leucopenia was 88.9 %, 87.4 %, and 88.6 %, respectively (all

p > 0.05 for any two compared groups).
We performed multivariate analysis to investigate
whether leucopenia could be a marker of improved OS
and DMFS (Table 3). Leucopenia and other prognostic
factors, i.e., age, sex, T classification, N classification, pathological type, type of chemotherapy, paclitaxel use, and type
of RT were included in the multivariate analysis, which determined that leucopenia, sex, T classification, and N classification were independent prognostic factors for OS and
DMFS. Compared to patients without leucopenia, the hazard ratios (HRs) of death for patients with mild and severe
leucopenia were 0.69 [95 % confidence interval (95 %CI)
0.56-0.85, p < 0.001] and 0.75 (95 %CI 0.59-0.95, p = 0.019),
respectively. The HR of distant metastasis for patients with
mild and severe leucopenia were 0.77 (95 %CI 0.61-0.96,
p = 0.023) and 0.99 (95 %CI 0.77-1.29, p = 0.995), respectively. When we compared patients with mild leucopenia to
patients with severe leucopenia, the HRs of death and distant metastasis were 0.93 (95 %CI 0.77-1.11, p = 0.416) and
0.77 (95%CI 0.64-0.93, p = 0.006), respectively.
9
When pretreatment leukocyte count (10 10 /L
9
vs. >10 10 /L) was included in the Cox model, leucopenia remained significant for OS (mild leucopenia:
HR = 0.70, 95 %CI 0.57-0.86, p = 0.001; severe leucopenia: HR = 0.76, 95 %CI 0.59-0.97, p = 0.026) and DMFS
(mild leucopenia: HR = 0.77, 95 %CI 0.61-0.96, p = 0.023;
severe leucopenia: HR = 0.99, 95 %CI 0.77-1.30, p = 0.995).
Tables 2 and 3 depict the subgroup analysis results for
patients who received <4 and 4 chemotherapy cycles.
Mild and severe leucopenia tended to be associated with
improved survival in patients who received <4 or 4
chemotherapy cycles.

Discussion

Fig. 1 KaplanMeier survival curves of (a) Overall Survival, (b)

Locoregional Relapse-free Survival, and (c) Distant Metastasis-free
Survival according to severity of leucopenia

In this study, we found that survival was improved in patients who developed leucopenia during chemoradiotherapy for ANPC. Patients with mild leucopenia had better
OS and DMFS than those with severe leucopenia. Leucopenia was an independent prognostic factor for OS and
DMFS in patients who received <4 and 4 chemotherapy
cycles. This is the first instance that has been reported in
pretreated ANPC.
As far as we know, leucopenia or neutropenia indicates
that the chemotherapeutic agent dose is sufficient to cause
bone marrow suppression and an anti-tumor effect [8, 9].
The absence of leucopenia or neutropenia indicates an absent or weak biological effect of chemotherapy, likely indicating that the dose is too low. On the other hand, severe
leucopenia may indicate overdosage. High-dose chemotherapy does not improve survival, and impairs patient
quality of life [28]. We speculate that moderate-dose
chemotherapy, as evidenced by moderate toxicity, is the
optimal treatment, correlating with better survival than

Table 3 Multivariate analysis of survival for patients with ANPC

All population

Cycles <4 population

Cycles > =4 population

OS

DMFS

OS

DMFS

OS

DMFS

HR(95 %CI)a

0.69(0.56-0.85)

0.77(0.61-0.96)

0.70(0.55-0.89)

0.88(0.63-1.23)

0.73(0.46-1.15)

0.61(0.40-0.94)

<0.001

0.023

0.003

0.452

0.174

0.025

HR(95 %CI)a

0.75(0.59-0.95)

0.99(0.77-1.29)

0.82(0.60-1.11)

0.79(0.61-1.03)

0.97(0.74-1.27)

0.84(0.53-1.32)

0.019

0.995

0.204

0.083

0.828

0.446

HR(95 %CI)a

0.93(0.77-1.11)

0.77(0.64-0.93)

0.85(0.66-1.09)

0.90(0.68-1.19

0.71(0.46-1.07

0.73(0.56-0.96)

0.416

0.006

0.204

0.469

0.108

0.026

HR(95 %CI)

0.67(0.55-0.81)

0.70(0.58-0.86)

0.66(0.52-0.84)

0.73(0.57-0.93)

0.66(0.48-0.91)

0.68(0.49-0.94)

<0.001

<0.001

0.001

0.013

0.010

0.019

HR(95 %CI)

1.82(1.57-2.12)

1.05(0.89-1.23)

1.88(1.55-2.28)

1.09(0.89-1.34

1.71(1.34-2.17)

1.03(0.81-1.33)

<0.001

0.532

<0.001

0.367

<0.001

0.783

HR(95 %CI)

1.49(1.35-1.66)

1.33(1.19-1.47)

1.51(1.33-1.72)

1.36(1.19-1.56)

1.49(1.26-1.76)

1.27(1.08-1.51)

<0.001

<0.001

<0.001

<0.001

<0.001

0.005

HR(95CI)

1.77(1.62-1.93)

1.78(1.62-1.97)

1.92(1.71-2.16)

1.92(1.68-2.18)

1.56(1.35-1.80)

1.63(1.40-1.90)

<0.001

<0.001

<0.001

<0.001

<0.001

<0.001

Variable
Leucopenia
Mild VS Absent

Severe VS Absent

Mild VS Severe

Gender

Age

T-classification

N-classification

Abbreviations: OS: overall survival; DMFS: distant metastasis-free survival; HR: hazard ratio; CI: confidence interval; ANPC: advanced nasopharyngeal carcinoma
a
Adjusted for age (<45 and 45 years old), sex, T classification (T1/T2/T3/T4), N classification (N0/N1/N2/N3), pathological type, type of radiotherapy, type of
chemotherapy, and paclitaxel use

under- or overdosage. Colleoni et al. [29] found that patients who received level II doses (65-84 % of the prescribed dose) had longer disease-free survival (DFS) and
OS than patients who received higher (level I: >85 % of
the prescribed dose) or lower (level III: <65 % of the
pre- scribed dose) doses (p = 0.07, p = 0.03, respectively).
Add- itionally, Brunetto et al. reported that there
was no difference in OS for patients whose dose had
been re- duced compared to patients whose dose had
been main- tained [30]. Nakatat al. [17] and Shitara et
al. [15] both found that patients with mild neutropenia
had better
out- comes than those with severe
neutropenia; others have re- ported that patients who
developed grade 23 leucopenia or neutropenia had
significantly better prognosis than those with grade 4
leucopenia or neutropenia [16, 17, 31]. Our results agree
with these results. In other words, mild leucopenia or
neutropenia might be a barometer of the appropriate
chemotherapeutic dosage to obtain sufficient anti-tumor
effect in a patient, leading to improved clinical outcome;
however, severe leucopenia or neutropenia might be
a marker of overdosage and suboptimal survival.

However, there are differing findings: Kim et al. [22]

reported that neutropenia was not a significant prognostic indicator of improved progression-free survival and
OS (p = 0.180, p = 0.698, respectively) in stage I-IIIB
breast cancer. Kumpulainen et al. [23] drew a wholly different conclusion, where the 10-year DFS in FIGO
(International Federation of Obstetrics and Gynecology)
stage IC-IV disease was 45 % in patients with lower
leukocyte counts (<2.5 109/L) and 66 % in patients
9
with higher leukocyte counts (2.5 10 /L) (p < 0.05).
The probable reason is that the different disease stages
might obscure the impact of leucopenia. Most studies
and ours studied patients with advanced-stage disease.
Several reports have stated that pretreatment high
leukocyte or neutrophil count might be a poor prognostic indicator and that leucopenia or neutropenia are less
likely to occur during treatment [32, 33]. However, in
our multivariate analysis, which included this factor,
leucopenia remained significant for OS and DMFS.
Due to the retrospective nature of our study, there are
some limitations. First, the chemotherapy regimens and

dose varied. Second, patients were identified from 2005 to

2010, and the normal range of hematological profiles may
have varied. Third, although G-CSF was not used for
prophylaxis, it would nevertheless affect the severity of
leucopenia. Fourth, we only analyzed leucopenia, a sign of
myelosuppression. Taking hemoglobin
and platelet
inhib- ition into account might reflect the relationship
between myelosuppression and prognosis
more
accurately.

3.
4.

5.

6.

Conclusions
Leucopenia during chemoradiotherapy of ANPC is
strongly associated with better OS and DMFS; mild
leucopenia indicates better survival than severe leucopenia. This may indicate that mild leucopenia is a surrogate marker for adequate chemotherapeutic dose. We
can identify the patients who may benefit from chemotherapy if they experienced leucopenia during the treatment. The chemotherapy dose should not only depend
on the body surface area, but also be based on its toxic
effects. Prospective trials are required to assess whether
dosing adjustments based on leucopenia may improve
chemotherapy efficacy.
Abbreviations
ANPC: Advanced nasopharyngeal carcinoma; CRT: Conventional radiotherapy;
IMRT: Intensity modulated radiation therapy; NCCN: National comprehensive
cancer network; G-CSF: Granulocyte colony-stimulating factor; MRI: Magnetic
resonance imaging; ECT: Emission computed tomography; CT: Computed
tomography; IC: Induction chemotherapy; CC: Concurrent chemotherapy;
AC: Adjuvant chemotherapy; HR: Hazard ratio; CI: Confidence interval;
OS: Overall
survival; DMFS: Distant metastasis-free survival;
LRFS:
Locoregional relapsefree survival;
DFS: Disease-free
survival; FIGO:
International federation of obstetrics and gynecology; WHO: World health
organization.

7.
8.
9.
10.
11.
12.
13.
14.

15.

16.
Competing interests
The authors declare that they have no competing interests.
Authors contributions
SZ checked data, drafted the manuscript and performed the statistical
analysis. OYPU, TJ and LXW collected the data. XFY participated in the
design of the study. MYP conceived of the study, and participated in its
design and coordination and helped to draft the manuscript. All authors
read and approved the final manuscript. Both Zhen Su and Yan-Ping Mao
contributed equally to this manuscript.
Acknowledgements
This work was supported by grants from the National Natural Science
Foundation of China (No. 81201746), Planned Science and Technology
Project of Guangdong Province (2012B031800092), Medical Science
Foundation of Guangdong Province (No. B2012135), Cultivating Foundation
of Education-bureau of Guangdong Province (No. LYM11001).

17.

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Received: 16 October 2014 Accepted: 15 May 2015

21.
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