Abstract Objective: Febrile neutropenia (FN) is a major toxic responseto chemotherapy requiring prompt medical attention. There are a limited number of reports on clinical outcome in patients with FN that present to emergency departments. Materials and Methods: We retrospectively evaluated clinical manifestations, therapeutic outcomes, and risk factors for FN in 102 adult patients that presented to the emergency department between 1 January 2006 and 31 March 2009. FN was defined as a body temperature&gt;38°C and a neutrophil count &gt;0.5×10 9 /L on the day of fever onset or the day after. Results: Mean age of the patients was 57 years. Mean absolute neutrophil count (ANC) was 436.8/mm 3 (range: 0-1000/mm 3 ). In all, 23 of the patients (22.5%) died due to complications related to FN. There were not a statistical difference in therapeutic outcome among tumor types, performance status, sex, depth of neutropenia, or time from emergency department presentationto initiation of antibiotic therapy. Age was an important prognostic factor for therapeutic outcome. Mean age of fatal cases was 65 years versus 56 years for non-fatal cases (p=0.016). Bacteremia was noted in 19 patients, 10 (53%) of which died. The mortality rate was significantly higher in thepatients with blood culture-proven bacteria than in those whose blood culture yielded no organism (p=0.013). Conclusion: FN patients that presented to the emergency department had a high mortality rate that increased with age. Given the increasing age of patients diagnosed with cancer as well as therapeutic interventions, the high mortality rate associated withchemotherapy-induced FN in elderly patients requires further study in order to reduce the risk of death. (Turk J Hematol 2011; 28: 193-7

Dong Wun Shin

Hoon Kim

Joo Han Lim

Kyung Hwan Kim

Moon Hee Lee

Woong Gil Choi

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193Research Article  
Outcomes in 102 patients that present to the 
emergency department with chemotherapy-
induced febrile neutropenia 
Kemoterapi kaynaklı febril nötropeni şikâyetiyle acil servise başvuran 
102 hastanın sonuçları 
Joo Han Lim1, Hoon Kim2, Woong Gil Choi3, Kyung Hwan Kim2, Dong Wun Shin2, 
Moon Hee Lee1
1Department of Internal Medicine, Faculty of Medicine, Inha University, Incheon, Korea
2Department of Emergency Medicine, Inje University Ilsan Paik Hospital, Goyang, Korea
3Department of Internal Medicine, Konkuk University Hospital, Chungju, Korea
Address for Correspondence: Prof. Hoon Kim, 2240 Daehwa-dong, Ilsan Seo-gu, Goyang-si, Gyeonggi-do, Korea Goyang-si - Korea 
Phone: +82-31-910-9782 E-mail: megali@hanmail.net
doi:10.5152/tjh.2011.53
Abstract
Objective: Febrile neutropenia (FN) is a major toxic responseto chemotherapy requiring prompt medical 
attention. There are a limited number of reports on clinical outcome in patients with FN that present to 
emergency departments.
Materials and Methods: We retrospectively evaluated clinical manifestations, therapeutic outcomes, and 
risk factors for FN in 102 adult patients that presented to the emergency department between 1 January 
2006 and 31 March 2009. FN was defined as a body temperature>38°C and a neutrophil count 
>0.5×109/L on the day of fever onset or the day after.
Results: Mean age of the patients was 57 years. Mean absolute neutrophil count (ANC) was 436.8/mm3 
(range: 0-1000/mm3). In all, 23 of the patients (22.5%) died due to complications related to FN. There 
were not a statistical difference in therapeutic outcome among tumor types, performance status, sex, 
depth of neutropenia, or time from emergency department presentationto initiation of antibiotic therapy.
Age was an important prognostic factor for therapeutic outcome. Mean age of fatal cases was 65 years 
versus 56 years for non-fatal cases (p=0.016). Bacteremia was noted in 19 patients, 10 (53%) of which 
died. The mortality rate was significantly higher in thepatients with blood culture-proven bacteria than 
in those whose blood culture yielded no organism (p=0.013).
Conclusion: FN patients that presented to the emergency department had a high mortality rate that
increased with age. Given the increasing age of patients diagnosed with cancer as well as therapeutic
interventions, the high mortality rate associated withchemotherapy-induced FN in elderly patients
requires further study in order to reduce the risk of death. (Turk J Hematol 2011; 28: 193-7)
Key words: Neutropenia,fever, emergency department, chemotherapy
Received: December 09, 2010   Accepted: March 28, 2011 
Introduction
The association between neutropenia and infec-
tion, which inevitably develop following chemo-
therapy, is a frequent cause of morbidity and mortal-
ity in cancer patients [1,2]. Chemotherapy-induced 
febrile neutropenia (FN) is one of the most impor-
tant and potentially life-threatening oncologic emer-
gencies, which requires prompt medical assess-
ment and treatment with antibiotics. In febrile 
patients with neutropenia, body fluids should be 
obtained for cultures and treatment with broad-
spectrum antibiotics should be started. It was recent-
ly reported that the prevalence of gram-positive 
infection in cancer patients with FN is increasing [3]. 
Although the standard of care is to treat FN as an 
oncologic emergency, patients generally wait for 
prolonged periods before receiving the necessary 
treatment. Prior to the present study, few data have 
been collected regarding the outcome of patients 
with FN that present to an emergency department 
(ED). Additional research is therefore required in 
order to examine the characteristics and outcome in 
patients that visited an ED due to chemotherapy-
induced FN and to identify the risk factors associat-
ed with mortality in these patients. Accordingly, the 
present study retrospectively analyzed the charac-
teristics and outcomes in patients with chemothera-
py-induced FN that presented to our ED. 
Methods and Materials
We retrospectively evaluated clinical manifesta-
tions, outcomes, and risk factors for FN following 
chemotherapy in 143 solid adult tumor and lym-
phoma patients between 1 January 2006 and 31 
March 2009. Patients were selected for inclusion in 
the study based on the diagnosis of neutropenia 
and fever. Fever was defined by the criteria given in 
the Infectious Disease Society Guidelines, which is 
a fever >38°C for more than 1 h or any single tem-
perature measurement >38.3°C [4,5]. Patients that 
did not receive chemotherapy were excluded from 
the analysis, as were those that were not febrile or 
neutropenic. Patients whose neutropenia and fever 
were diagnosed in the hematology and oncology 
department clinics were admitted to hospital direct-
ly without an ED visit and were likewise not includ-
ed in this study. We defined FN as a body tempera-
ture >38°C and a neutrophil count ≤0.5×109/L on 
the same day as fever onset or the day after. 
ED records for consecutive oncology patients 
with FN were reviewed and mortality, intensive care 
unit (ICU) use, blood culture results, time from ED 
Özet
Amaç: Febril nötropeni (FN), uygun tıbbi tedaviyi gerektiren kemoterapiye bağlı gelişen önemli bir toksik 
yanıttır. Acil servise başvuran FN’li hastalarda klinik sonuçlara yönelik sınırlı sayıda bildiri mevcuttur.
Gereçler ve Yöntemler: 1 Ocak 2006 ile 31 Mart 2009 arasında acil servise gelen 102 erişkin FN has-
tasında klinik belirtiler, tedavi sonuçları ve FN için risk faktörleri geriye dönük olarak değerlendiril-
miştir. FN >38°C vücut sıcaklığı ve ateş başladığı gün veya ertesi günde >0.5×109/L nötrofil sayısı 
olarak tanımlanmıştır. 
Bulgular: Hastaların yaş ortalaması 57’dir. Ortalama mutlak nötrofil sayımı (ANC) 436.8 mm/3’dir 
(aralık: 0-1000/mm3). Genel anlamda hastaların 23’ünde (%22.5) FN ile ilişkili komplikasyonlar nede-
niyle ölüm meydana gelmiştir. Tümör tipleri, performans durumu, cinsiyet, nötropeni ağırlığı veya acil 
duruma gelmeden antibiyotik tedavisine başlanmasına kadar geçen süre arasında tedavi sonuçları 
açısından istatistiksel bir fark görülmemiştir. Yaş tedavi sonuçları yönünden önemli bir prognoz faktö-
rüdür. Ölümcül olgularda ortalama yaş 65 iken ölümcül olmayanlarda 56’dır (p=0.016). Bakteriemi 
19 hastada gözlenmiş olup bunlardan 10’u ölmüştür (%53). Kan kültürüyle bakterinin kanıtlandığı 
hastalarda ölüm oranı, kan kültürü ile bir organizma gösterilemeyen hastalara göre anlamlı bir şekilde 
daha yüksektir (p=0.013). 
Sonuç: Acil servise başvuran FN hastalarında yaş ilerledikçe daha yüksek bir ölüm oranı gözlenmiştir. 
Kanser tanısı konulan hastalarda ileri yaş ve yanı sıra tedavi girişimleri göz önüne alınarak, yaşlı hastalarda 
kemoterapi kaynaklı FN ile ilişkili yüksek ölüm oranının azaltılması için daha fazla çalışma gerekmektedir.
(Turk J Hematol 2011; 28: 193-7)
Anahtar kelimeler: Nötropeni, ateş, acil servis, kemoterapi
Geliş tarihi: 09 Aralık 2010   Kabul tarihi: 28 Mart 2011 
Lim et al.
Chemotherapy-induced febrile neutropenia in the emergency department Turk J Hematol 2011; 28: 193-7194
presentation and administration of empirical antibi-
otics, and age were recorded. ED and subsequent 
inpatient records were also reviewed for the follow-
ing: vital signs, symptoms, physical findings, sus-
pected source of infection in the ED, white blood 
cell count (WBC) or absolute neutrophil count 
(ANC), chest radiograph results, urinalysis results, 
hospital course, use of granulocyte colony-stimulat-
ing factor (G-CSF), blood, urine, or other culture 
results, and outcome. The time from fever onset to 
ED presentation was defined as the time from the 
onset of subjective symptoms (based on patient his-
tory) and presentation to the ED. The time from ED 
to antibiotic administration was defined as the time 
from presentation to the ED and the commence-
ment of antibiotic therapy.
Treatment 
We performed blood cultures as soon as possible 
in patients suspected of FN in the ED. Empirical anti-
biotics (3rd- or 4th-generation cephalosporin in com-
bination with aminoglycoside) were administered to 
most of the patients. If FN was accompanied by renal 
insufficiency, ciprofloxacin was used as an empirical 
antibiotic in preference to aminoglycoside. 
Statistical analysis
The survival rate, as the treatment outcome, was 
analyzed using the Kaplan-Meier method, with the 
date of presentation to the ED as the starting date. 
We also performed Cox regression analysis using 
the following variables: age, sex, time from ED pre-
sentation to the start of antibiotic therapy, the effect 
of G-CSF, cancer type (solid tumor or lymphoma), 
and performance status. All statistical analyses 
were conducted using SPSS v.12.0 software (SPSS, 
Chicago, IL). A p value of less than 0.05 was consid-
ered to be statistically significant.
Results
Patient characteristics
We analyzed 102 patients that presented to our 
ED due to chemotherapy-induced FN between 1 
January 2006 and 31 March 2009. The characteris-
tics of these patients are summarized in Table 1. 
The Eastern Cooperative Oncology Group (ECOG) 
performance status of the patients was as follows: 
20 patients had a performance status of 2, 67 had a 
performance status of 1, and 15 had a performance 
status of 0. Mean age of the patients was 57 years 
(range: 25-84 years) and 53% were male. Mean ANC 
was 436.8 mm3 (range: 0-1000 mm3); 4 patients had 
an ANC <10 mm3. 
Treatment and survival outcome
Survival of elderly patients (≥65) was inferior to 
that of the younger patients (<65). Mean age of the 
patients that died due to an FN event (65 years) was 
significantly (p=0.016) higher than that of the patients 
that didn’t (56 years). There wasn’t a difference in the 
outcome of FN between patients with lymphomas 
and those with solid tumors. Median time from the 
onset of fever to ED presentation was 24 h; the differ-
ence between the patients that died and survived 
was not significant (Table 2). We also analyzed the 
patients according to those that presented to the ED 
within 24 h of the onset of fever and after 24 h; how-
ever, there wasn’t a significant difference in outcome 
between these 2 groups. Median time from ED pre-
sentation to the start of antibiotic therapy was 
approximately 2 h (110 min; range: 0.6-13.3 h), and 
there wasn’t a significant difference between the 
patients that died and those that survived. 
Lim et al.
Chemotherapy-induced febrile neutropenia in the emergency departmentTurk J Hematol 2011; 28: 193-7 195
Table 1. Patient characteristics
Total Patients n=102
Sex
 Male 50 (49%)
 Female 52 (51%)
Median age, years 57
Cancer Type
 Lymphoma 30 (29.4%)
 Solid Tumor 72 (70.6%)
ANC median, number/mm3 90 (range; 5-760)
 ANC ≤100 mm3 53 (52%)
 ANC >100 mm3 49 (48%)
Symptom to ED time 
 ≤ 24hr 49 (48%)
 > 24hr 53 (52%)
Median ED to Antibiotics time (min) 110 (range; 35-615)
Blood culture result
 Bacteremia 19 (18.6%)
 gram-positive 6 (5.9%)
 gram-positive 13 (512.7%)
 No growth 80 (70.4%)
 No culture 3 (2.9%)
Among the patients that presented to the ED out-
side regular working hours, the time from ED pre-
sentation to the start of antibiotic therapy was lon-
ger than that in patients that presented during regu-
lar working hours; however, the difference was not 
statistically significant and there was no difference 
in the outcome of FN. In all, 24 patients (23.5%) 
required ICU management, of which 18 (75%) died 
due to complications associated with FN. Patients 
with FN that required ICU care had a significantly 
higher mortality rate than those did not require ICU 
care (p<0.05). Patients treated in the ICU were 
older than those treated in a general ward (median 
age: 68 vs. 55, respectively). 
We also analyzed the relationship between blood 
culture positivity and treatment outcome. In total, 
19 patients had blood culture-positive results; 6 had 
gram-positive bacteremia and 13 had gram-nega-
tive bacteremia. Figure 1 shows the microorgan-
isms isolated via blood culture. The 19 patients with 
bacteremia were initially treated with the 3rd-gener-
ation antibiotics cephalosporin and aminoglyco-
side, except 2 patients highly suspected for gram-
positive infection (1 patient had phlebitis and 1 
patient had catheter-related infection). The mortal-
ity rate was significantly higher among the culture-
positive patients than among those whose blood 
culture yielded no organism (47.4% versus 16.3%, 
p=0.013). In total, 23 patients died due to an infec-
tion associated with FN. The patients that died were 
significantly older than those that survived. 
Discussion
Chemotherapy-induced neutropenia is a com-
mon toxicity that increases patient risk of morbidity 
and mortality, and may compromise the effective-
ness of treatment via a reduction in chemotherapy 
dose intensity or dose density [6]. In the present 
study advanced age, necessity of ICU care, and bac-
teremia (confirmed by blood culture) were risk fac-
tors for mortality in the patients that presented to our 
ED with chemotherapy-induced FN. Intensive educa-
tion for patients that receive chemotherapy began at 
our hospital in 2005. The education we provide 
includes information on nutrition, chemotherapy tox-
icity, and conditions that should prompt presentation 
to hospital. A fever >38°C is emphasized as a major 
side effect that necessitates immediate medical 
assessment; however, only 34 of the patients in the 
present study received individual education regard-
ing chemotherapy and its toxicity. There was a statis-
tically significant difference in outcome between the 
patients that received education and those that did 
not. It would nevertheless be imprudent to conclude 
that intensive education contributed to the survival of 
patients with FN; however, there is no doubting the 
value of education for cancer patients scheduled to 
receive cytotoxic chemotherapy. 
Many researchers are now exploring alternatives 
to the standard approach to treating FN, including 
prophylactic oral antibiotic treatment, administra-
tion of prophylactic hematopoietic growth factors, 
and even oral antibiotic therapy for low-risk outpa-
tients [7-10]. 
As the present study used retrospective analysis 
of data obtained at only 1 academic institution that 
treats patients with malignancies, it might not 
Lim et al.
Chemotherapy-induced febrile neutropenia in the emergency department Turk J Hematol 2011; 28: 193-7196
Table 2. Comparison of the patients that died and survived
  Survived Died p
Age (years) 56 (25-84) 65 (45-84) 0.016
 Blood Culture Results n n
 Bacteremia 10 9 0.013
 non-bacteremia 67 13 
 Cancer Type n n
 Lymphoma 22 8 0.521
 Solid 57 15 
 Absoulte Neutrophil Count n n
 ANC <100 44 9 0.162
 ANC >100 35 14 
 Time of symptom to ED n n
 Symptom to ED <24h 52 13 0.414
 Symptom to ED >24h 27 10
Figure 1. Culture results isolated in the patients with bacteremia
reflect care in the community at large or that at 
other institutions. The retrospective design of the 
present study and the small sample involved should 
be taken into account when making inferences and 
recommendations based on the findings. 
In conclusion, we analyzed the outcome of 
patients that presented to our ED due to chemother-
apy-induced FN. We observed considerable mortal-
ity, particularly in the elderly patients. Given the 
increasing age of adults diagnosed with cancer that 
undergo chemotherapy, and the heightened risk of 
FN among elderly patients, further prospective stud-
ies are warranted in order to establish a more 
appropriate management strategy for chemothera-
py-induced FN, and for reducing the incidence of 
mortality and morbidity due to chemotherapy. 
Acknowledgment
IRB committee of Inha university hospital 
approved our study. IRB committee approval is 
same an ethical committee approval.
Conflict of interest statement
The authors of this paper have no conflicts of 
interest, including specific financial interests, rela-
tionships, and/or affiliations relevant to the subject 
matter or materials included.
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Lim et al.
Chemotherapy-induced febrile neutropenia in the emergency departmentTurk J Hematol 2011; 28: 193-7 197


Outcomes in 102 patients that present to the emergency department with chemotherapy- induced febrile neutropenia Kemoterapi kaynaklı febril nötropeni şikâyetiyle acil servise başvuran 102 hastanın sonuçları

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Outcomes in 102 patients that present to the emergency department with chemotherapy- induced febrile neutropenia Kemoterapi kaynaklı febril nötropeni şikâyetiyle acil servise başvuran 102 hastanın sonuçları

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