Pediatr Blood Cancer

Significant Inconsistency Among Pediatric Oncologists in theUse of the Neutropenic Diet

Lauren E. Braun, RD,1 Heidi Chen, PhD,2 and Haydar Frangoul, MD3*

INTRODUCTION

Although it is well known that nutrition status plays an important

role in the care of oncology patients, there continues to be a lack

of standardized nutrition guidelines related to the care of these

patients. Pediatric oncology patients are often at an increased

nutritional risk due to intensive treatment regimens which can

increase metabolic needs. During treatment, patients may experi-

encemucositis, xerostomia, changes in taste, diarrhea, constipation,

nausea, and vomiting [1]. Various nutrition interventions for these

patients can include oral supplements, appetite stimulants, enteral

and parenteral nutrition, and a low bacteria or neutropenic diet for

immunosuppressed patients. A survey of 233 Children’s Oncology

Group (COG) institutions was conducted in 2006 in order to

identify the standards of practice in the nutritional management of

children with cancer. Fifty-four percent of institutions responded to

the survey. The authors found no consistency in the provision of

nutrition services and the assessment of nutritional status does not

routinely occur. Institutions rely upon different guidelines when

categorizing malnutrition and when nutritional intervention is

clinically indicated, a variety of approaches are employed [2].

Neutropenia places patients at an increased risk for infection and

many pediatric cancer centers place these patients on a neutropenic

diet [3]. The neutropenic diet is used in an effort to decrease the

exposure to potential harmful bacteria and decrease the risk of

infection in immunosuppressed patients. Use of the neutropenic diet

remains controversial and standardized guidelines for this diet have

not been universally implemented [4,5]. Current practices with the

neutropenic diet vary among pediatric healthcare facilities in

regards to specific diet restrictions, patient population (neutropenic

non-SCT patients vs. SCT patients) for which a modified diet is

implemented, parameters for diet initiation, and diet precautions at

home. Typical neutropenic diet restrictions include the avoidance of

deli meats, undercooked meats, raw fruits and vegetables, well

water, powdered infant formula, and unpasteurized dairy products;

however, research regarding the use of the diet is limited. A recent

article by Fox and Freifeld proposed transitioning from the

neutropenic diet to a more standardized approach of safe food

handling to allow for a less restrictive diet in the setting of

immunosuppression [3].

In a survey of adult community cancer centers, the authors

identified significant variability in diet implementation and dietary

restrictions during the neutropenic phase [6]. Due to the lack of data

in pediatric oncology and stem cell transplant (SCT) recipients on

the use of the neutropenic diet, we surveyed pediatric oncologist

who are members of COG. We sought to determine the practice

across pediatric cancer centers with the implementation of the

neutropenic diet and to determine factors influencing current

practices in an effort to standardize the care of pediatric oncology

and transplant patients.

METHODS

Study Population

The COG website was used to identify pediatric oncologists by

using stem cell transplantation and hematology/oncology as

discipline search criteria. Eligibility requirements for survey

participation were COG membership in 2013 and current

involvement in clinical care of patients. No compensation was

offered for participation and survey responses were anonymous.

Background. The role of the neutropenic diet in the developmentof infections in oncology and stem cell transplant (SCT) patients iscontroversial. There is no data on the use of the neutropenic dietamong pediatric oncologists.Methods. A self-administered electron-ic survey was sent to 1,639 pediatric oncologists at 198 institutionswho are members of Children’s Oncology Group. A pediatricdietitian and pediatric oncologists developed, pretested, andmodified the survey for item clarification. Results. Five hundredfifty-seven physicians (34%) responded representing 174 (87%) of the198 member institutions. More than half of respondents (57%) reportimplementing the neutropenic diet at their facility. In a multivariateanalysis, being a stem cell transplant (SCT) center was the onlysignificant factor associated with implementing a neutropenic diet(OR: 6.06, 95% CI, 2.88–12.738, P<0.001) after controlling for

years in practice, gender, center size, and academic versus privatepractice. Among physicians who implemented a neutropenic diet,absolute neutrophil count was the trigger for initiating the diet inoncology patients (72%) while admission and start of preparativeregimen was used for SCT patients (84%). The majority ofrespondents (82%) stop the neutropenic diet when oncology patientsare no longer neutropenic while the practice varied significantly withSCT patients. Providers at the same institution were not consistentwith implementation of the diet, patient populations placed on theneutropenic diet and parameters for initiation, discontinuation of thediet and specific food restrictions. Conclusion. The implementationof the neutropenic diet by pediatric oncologists remains quitevariable even among those at the same institution. Pediatr BloodCancer # 2014 Wiley Periodicals, Inc.

Key words: neutropenic diet; pediatric oncologists; stem cell transplant

1Department of Clinical Nutrition, Vanderbilt University Medical

Center, Nashville, Tennessee; 2Department of Biostatistics, Vanderbilt

University Medical Center, Nashville, Tennessee; 3Department of

Hematology Oncology, Vanderbilt University Medical Center, Nash-

ville, Tennessee

Grant sponsor: Carolyn Perot Rathjen Chair in Pediatrics, Nashville,

TN (H.F.)

Conflict of interest: The authors declare no competing financial

interests.

�Correspondence to: Haydar Frangoul, Department of Hematology

Oncology, Vanderbilt University Medical Center, 397 PRB Nashville,

TN 37232-6310. Email: haydar.frangoul@vanderbilt.edu

Received 26 January 2014; Accepted 28 April 2014

�C 2014 Wiley Periodicals, Inc.DOI 10.1002/pbc.25104Published online in Wiley Online Library(wileyonlinelibrary.com).

Participation was voluntary and participants were not required to

respond.

Survey

The survey was developed by pediatric oncologists and a

registered dietitian. The survey was constructed and delivered

using REDCap, a secure, web-based application for building and

managing online surveys and databases. The survey was pilot tested

among local pediatric oncologists and modified for item clarifica-

tion. The surveywas comprised of 18 questions, most of whichwere

multiple choice. Questions relating to food restrictions allowed the

respondent to select all foods that applied. Survey questions focused

on physician-specific baseline data, use of the neutropenic diet,

parameters for initiating and discontinuing the diet and foods

restricted on the diet if the neutropenic diet is used. The survey

study was evaluated and approved by the institutional review board

at Vanderbilt University Medical Center.

Physicians received an email with a preliminary message

explaining the purpose of the study and included a link to the online

survey in April 2013. Email reminders were sent once a week to

non-responders requesting their participation in the survey.

Statistical Analysis

Descriptive statistics, including median and inter-quartile

ranges (IQR) for continuous variables, as well as percentages

and frequencies for categorical variables, were presented for

characteristics of respondents. Group comparisons were analyzed

using chi-squared, Wilcoxon, or Kruskal–Wallis tests. Fleiss Kappa

was employed to assess the consistencies among practitioners on

the type of food allowed when using a neutropenic diet within each

institution.Multivariable logistic regressionwas applied to evaluate

the association between factors of interest and the use of the

neutropenic diet and the institution cluster effect was adjusted by

robust sandwich estimator.

RESULTS

There were 1,639 physicians who met the inclusion criteria and

557 (34%) responded to the survey. These providers represent 174

(87%) of the 198 member institutions in COG. Characteristics of

survey respondents are shown in Table I. The median number of

years of practice among physicians who responded to the survey

is 11 years (range 0–46 years). Respondents to the survey were

equally divided between males (50%) and females (50%).

Approximately half of respondents (47%) spent at least 75% of

their time practicing clinical pediatric oncology and (42%) reported

treating up to 75 new diagnoses per year at their institution. Most

(83%) practiced at an academic institution and the majority of

physicians (61%) report practicing at a facility that performs

pediatric allogeneic SCTs.

More than half of respondents (57%) report implementing the

neutropenic diet at their facility, 40% physicians report they do

not implement the neutropenic diet and 3% did not know. In a

univariable analysis, factors significantly influencing the use a

neutropenic diet include less years of practice (P¼ 0.006), female

gender (0.022), larger centers with 150 or more new diagnoses per

year (P< 0.001), academic centers (P¼ 0.001), and centers that

perform allogeneic SCTs (P< 0.001). The results of amultivariable

logistic regression indicated being a SCT center was the only factor

significantly associated with the use of the neutropenic diet

(OR: 6.06, 95% CI, 2.88–12.738, P< 0.001) (Table II).

Initiation of Neutropenic Diet

Among physicians who implement a neutropenic diet for

oncology patients, the majority (72%) initiate the diet based on

absolute neutrophil count (ANC), 12% initiate the diet upon

admission and 14% initiate at the start of chemotherapy. For those

respondents who initiate the neutropenic diet based on ANC, the

majority (86%) initiate when ANC<500/L, 9% initiate when ANC

<1,000/L and 5% initiatewhenANC<1,500/L. None of the factors

tested influenced the physician’s decision to start a neutropenic diet

in oncology patients including gender, years of practice, age, center

size, academic, or SCT center.

For physicians in centers that perform allogeneic stem cell

transplants, the majority implemented the diet upon hospital

admission or at the start of the preparative regimen (84%) compared

to 14% who initiate the diet based on ANC. For those respondents

that initiate the neutropenic diet based on ANC, the majority (89%)

TABLE I. Characteristics of Respondents and Factors Associated With Use of the Neutropenic Diet

ALL (N¼ 505) No (N¼ 210) Yes (N¼ 295) P-value

Median years of practice 11 (range 0–46) 13 10 0.006

Gender

Male 272 (50%) 113 (55%) 130 (45%) 0.002

Female 274 (50%) 92 (45%) 161 (55%)

Academic institution

No 87 (17%) 49 (24%) 37 (13%) 0.001

Yes 431 (83%) 157 (76%) 257 (87%)

Center size

�75 New diagnoses per year 221 (42%) 115 (55%) 102 (35%) <0.001

76–149 New diagnoses per year 144 (28%) 49 (24%) 88 (30%)

�150 New diagnoses per year 148 (28%) 44 (21%) 99 (34%)

Do not know 8 (2%)

Stem cell transplant center

No 199 (39%) 127 (61%) 69 (24%) <0.001

Yes 316 (61%) 81 (39%) 222 (76%)

Pediatr Blood Cancer DOI 10.1002/pbc

2 Braun et al.

initiate when ANC <500/L, 5% initiate when ANC <1,000/L and

5% initiate when ANC <1,500/L. None of the factors tested

influenced the physician’s decision to start a neutropenic diet in

transplant patients including gender, years of practice, age, center

size, academic, or SCT center.

Discontinuation of the Neutropenic Diet

The majority of respondents (82%) stop the neutropenic diet

when the patient is no longer neutropenic compared to 17% who

discontinue the diet upon discharge. Of physicians who use the

neutropenic diet in transplant patients, 12% stop the diet upon

discharge, 24% stop the diet when the patient is no longer

neutropenic, 35% stop the diet Dayþ100 post-transplant, and 29%

stop the diet at discontinuation of immunosuppression. Neither

physician gender, years of practice, age, center size, academic

nor SCT center significantly affected the decision to discontinue

the diet.

Neutropenic Diet Restrictions in the Hospital andat Home

The majority of respondents (81%) report allowing patients to

have food prepared outside the hospital. SCT centers were less

likely to allow food prepared outside the hospital compared to non-

transplant centers (P¼ 0.001). Fifty percent of respondents report

using the neutropenic diet even if the patient is at home. Significant

factors influencing the use of implementing the neutropenic diet at

home include physicians who have spent shorter time in practice

(P¼ 0.002), practicing in an academic center (P¼ 0.008), and

being a SCT center (P< 0.001).

Food/Beverage Restrictions on Neutropenic Diet

The survey provided physicians a list of foods and beverages to

better understand what is particularly restricted in the neutropenic

diet used in their centers. Among physicians who use the

neutropenic diet, they more commonly restricted fruits that cannot

be peeled, raw vegetables, herbs, and sprouts and unpasteurized

dairy. Unpasteurized dairy products and aged cheeses are the most

commonly restricted dairy products. Other dietary restrictions

included well water, sushi, and raw honey (Table III).

Consistency Among Pediatric Oncologists in Use of theNeutropenic Diet

To better evaluate the consistent approach of physician use of the

neutropenic diet within the same center, we evaluated the response

from centers that had more than one physician responding to the

survey. Based on a Fleiss Kappa score of <0 indicating less than

chance agreement, 0.01–0.2 indicating slight agreement, 0.21–0.4

indicating fair agreement, 0.41–0.6 indicating moderate agreement,

0.61–0.8 suggesting substantial agreement, and 0.81–1 suggesting

perfect agreement among responders, physicians within the same

institution were not consistent in implementation of the neutropenic

diet (0.35). Physicians were in moderate agreement regarding the

patient population that may be placed on this diet including

oncology patients (0.46), and in fair agreement with use among

SCT patients when neutropenic (0.25) and SCT patients regardless

of neutropenia (0.35). Answers were not consistent among

physicians within the same institution for initiation of the diet

for oncology patients (0.19) and initiation of the diet for SCT

patients (�0.03). Responses were also not consistent within the

same institution for when to discontinue the diet for oncology

patients (0.39) and SCT patients (�0.11). Food restrictions were not

consistent for takeout food (0.36), fast food (0.24), sushi (0.06), and

raw honey (0.01). Answers were not consistent within the same

institution if food from outside the hospital is allowed on the

neutropenic diet (0.46) and if neutropenic diet restrictions are

implemented at home (0.24). Survey results indicate that practices

not only vary among different institutions but also vary within the

same institution (Table IV).

DISCUSSION

This study represents the most comprehensive evaluation of

current practices regarding the use of the neutropenic diet among

pediatric oncologists. This study confirms current findings among

adult practitioners that use of the neutropenic diet continues to vary

significantly among pediatric healthcare providers. More than half

of respondents (57%) report using the neutropenic diet in their

facility; however, facilities vary significantly in regards to specific

diet restrictions, patient populations placed on the neutropenic diet

and parameters for initiation and discontinuation of the diet.

Despite the lack of data supporting the use of neutropenic diet in

patients receiving chemotherapy or SCT, many centers continue to

implement such diet. A recent survey by Smith and Besser of 156

institutions belonging to the Association of Community Cancer

Centers identified that 78% of centers used a neutropenic diet [6].

Initiation of a neutropenic diet varied with 43% of centers initiating

the diet when the ANC is<1,000, 46% when ANC is<500 and 9%

upon initiation of chemotherapy. More than 90% of the responders

restricted fresh fruits and vegetables. This is different than what we

have observed in our survey where 86% of those using the

neutropenic diet initiated the diet based on an ANC of less than 500.

In addition, the majority of our responders restrict some but not all

fresh fruits and vegetables.

There is clear lack of prospective data supporting the use of the

neutropenic diet in adult and pediatric patients. A recent study

by Gardner et al. [7] randomly assigned adult patients receiving

remission induction therapy for newly diagnosed acute myeloid

leukemia or high risk myelodysplastic syndrome to either a diet that

did not include raw fruits and vegetables (cooked fruits and

vegetables, 78 patients) or a diet that allowed fresh fruits and

TABLE II. Multivariate Analysis of Factors Associated With the

Use of the Neutropenic Diet

Variable OR 95% CI P-value

Median years of practice 0.997 0.976–1.019 0.817

Gender

Male Ref

Female 1.471 0.953–2.272 0.082

Academic institution

No

Yes 0.915 0.475–1.762 0.792

Center size

�75 New diagnoses per year Ref

76–149 New diagnoses per year 0.699 0.365–1.338 0.280

�150 New diagnoses per year 0.761 0.345–1.679 0.4990

Stem cell transplant center

No Ref

Yes 6.06 2.88–12.738 <0.001

Pediatr Blood Cancer DOI 10.1002/pbc

Neutropenic Diet in Children 3

TABLE IV. Consistency Among Pediatric Oncologists in Use of the Neutropenic Diet

n Fleiss Kappaa

Use of the neutropenic diet 131 0.35

Use of the neutropenic diet among

Neutropenic oncology patients (non-SCT) 135 0.46

SCT patients when neutropenic 135 0.25

SCT patients regardless of neutropenia 135 0.35

Initiation of the neutropenic diet for oncology patients (non-SCT) 22 0.19

Initiation of the neutropenic diet for stem cell transplant patients 56 �0.03

Discontinuation of the neutropenic diet for oncology pts (non-SCT) 44 0.39

Discontinuation of the neutropenic diet for stem cell transplant patients 61 �0.11

Neutropenic diet (food/beverage restrictions)

Infant formula (powder) 135 0.94

Takeout food 135 0.36

Fast food 135 0.24

Sushi 135 0.06

Raw honey 135 0.01

Pepper 135 0.71

Spices (seasonings added after cooking) 135 0.73

Food allowed from outside the hospital 87 0.46

Diet restrictions are implemented at home 125 0.24

aA Fleiss Kappa< 0 is considered less than chance agreement among responders, 0.01–0.2 is considered slight agreement, 0.21–0.40 is considered

fair agreement, 0.41–0.60 is considered moderate agreement, 0.61–0.80 suggests substantial agreement, and 0.81–1 suggests perfect agreement.

TABLE III. Food/Beverage Restrictions in the Neutropenic Diet

Category Restricted Not restricted P-value

Fruits/vegetables

Fresh fruits and juices 105 (35.6%) 190 (64.4%) <0.001

Fresh berries 200 (67.8%) 95 (32.2%) <0.001

Fruits that cannot be peeled 229 (77.6%) 66 (22.4%) <0.001

Raw vegetables 205 (69.5%) 90 (30.5%) <0.001

Fresh squeezed juices 104 (35.3%) 191 (64.7%) <0.001

Dried fruits 70 (23.7%) 225 (76.3%) <0.001

Raw herbs/sprouts 206 (69.8%) 89 (30.2%) 0.001

Do not know 48 (16.3%)

Dairy products

Yogurt with live active cultures 123 (41.7%) 172 (58.3%) 0.004

Unpasteurized dairy products 220 (74.6%) 75 (25.4%) <0.001

Aged cheeses 168 (56.9%) 127 (43.1%) 0.017

Do not know 59 (20%)

Protein sources

Deli meats 163 (55.3%) 132 (44.7%) 0.071

Nuts 63 (21.4%) 232 (78.6%) <0.001

Do not know 86 (29.2%) <0.001

Beverages

Herbal or flavored tea 45 (15.3%) 250 (84.7%) <0.001

Well water 188 (63.7%) 107 (36.3%) <0.001

Do not know 65 (22%)

Other

Infant formula (powder) 9 (3.1%) 286 (96.9%) <0.001

Takeout food 137 (46.4%) 158 (53.6%) 0.221

Fast food 143 (48.5%) 152 (51.5%) 0.6

Sushi 245 (83.1%) 50 (16.9%) <0.001

Raw honey 224 (75.9%) 71 (24.1%) <0.001

Pepper 59 (20%) 236 (80%) <0.001

Spices (seasonings after cooking) 36 (12.2%) 259 (87.8%) <0.001

Do not know 38 (12.9%)

Pediatr Blood Cancer DOI 10.1002/pbc

4 Braun et al.

vegetables (raw fruits and vegetables, n¼ 75 patients). Rates of

major infection and death were found to be similar and the authors

concluded that a neutropenic diet did not prevent major infections

or deaths [7]. In another prospective study, 28 adults were studied

and the rates of infections did not differ among those who were

compliant with the neutropenic diet as compared to those who did

not comply [1]. In a retrospective study of 726 adults undergoing

hematopoietic SCT patients those given neutropenic diet experi-

enced significantly higher rates of diarrhea and documented

infections compared to those receiving general hospital diet [8].

Many have advocated transitioning from the neutropenic diet to

a more standardized approach of safe food handling to allow for

a less restrictive diet in the setting of immunosuppression and

neutropenia [3,9–11]. In a prospective study in children receiving

myelosuppressive chemotherapy, patients were randomized to

either the neutropenic diet (n¼ 9) or Food and Drug Administra-

tion-approved food safety guidelines (n¼ 10). Infection rates were

found to be similar between the two groups [5]. Another important

variable to investigate with regard to use of the neutropenic diet

would be cost implications.

The lack of prospective studies and clear guidelines addressing

this issue especially in children is reflected in the variable responses

in our current study. It is interesting that centers with SCT programs

are more likely to use a neutropenic diet. This might be the result of

the influence of the SCT program on the entire center’s practice.

Although the variability in use of the neutropenic diet among

pediatric cancer centers has been widely known; more significantly,

our study revealed that current use and practices in regards to

the neutropenic diet even varies among providers within the

same institution. Survey results indicate that variability in use of

the neutropenic diet exists among physicians within the same

institution. Upon review of consistency among pediatric oncologists,

providerswithin the same institutionwere inconsistent in their report

of implementation of the diet, patient populations placed on the

neutropenic diet and parameters for initiation and discontinuation of

the diet and specific food restrictions. This data further highlights the

need for standardized guidelines with use of the neutropenic diet.

This study has some limitations. Non-response bias is a potential

limitation of all surveys; with an individual response rate of 34%

and an institutional response rate of 87%, our response rate

compares favorably with physician response rates. Non-

respondents may have different practice guidelines in regards to

diet restrictions, patient population for which a modified diet is

implemented, parameters for diet initiation, and restricted diet

precautions at home. Due to the lack of a standard definition of the

neutropenic diet, the variability in interpretation of the neutropenic

diet by physicians is a further limitation. Another potential

limitation of self-administered surveys is that self-reported practice

patterns may not reflect actual practice.

In summary, although the role of nutrition is widely recognized

as an essential component among pediatric oncology patients; there

continues to be a lack of standardized nutrition guidelines,

specifically in use of the neutropenic diet among pediatric cancer

centers and providers within the same institution. There is

significant effort through COG nutrition committee to standardize

practices among pediatric centers.

AUTHORS’ CONTRIBUTIONS

L.E.B., H.C., and H.F. conceived and designed the study,

analyzed and interpreted data, and wrote the manuscript; and all

authors gave final approval of the manuscript.

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