Leucopenia and treatment efficacy in advanced nasopharyngeal carcinoma

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 20–84 years); that
for female patients was 44 years (range 20–76 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 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).

Table 1. Patient characteristics according to grade of leucopenia

The median OS was 52.6 months (range 3.07–113.0 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 1–2) and
807 patients (21.1 %) developed severe leucopenia (grade 3–4); 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. Kaplan–Meier 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 5-year 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 leucopenia was 88.9 %, 87.4 %, and 88.6 %, respectively (all p??0.05 for any two compared groups).

Table 2. Univariate analysis of survival for patients with ANPC

Fig. 1. Kaplan–Meier survival curves of (a) Overall Survival, (b) Locoregional Relapse-free Survival, and (c) Distant Metastasis-free Survival according to severity of leucopenia

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.

Table 3. Multivariate analysis of survival for patients with ANPC

When pretreatment leukocyte count (?10?×?10⁹/L vs. 10?×?10⁹/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.