Significant inconsistency among pediatric oncologists in the use of the neutropenic diet
Transcript of Significant inconsistency among pediatric oncologists in the use of the neutropenic diet
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: [email protected]
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
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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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