Murray & Pindoria-2014

Nutrition support for bone marrow transplant patients
(Review)
Murray SM, Pindoria S
This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library
2009, Issue 1
http://www.thecochranelibrary.com
Nutrition support for bone marrow transplant patients (Review)

Copyright 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
AUTHORS CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
ACKNOWLEDGEMENTS
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 1.1. Comparison 1 Oral glutamine versus oral placebo studies, Outcome 1 Mean duration (+/-SD) of time in
hospital (e.g. admission to discharge or from day 0 to discharge).. . . . . . . . . . . . . . . .
Analysis 1.2. Comparison 1 Oral glutamine versus oral placebo studies, Outcome 2 Mean(+/-SD) number of days patients
had some degree of mucositis from start to end of study.. . . . . . . . . . . . . . . . . . . .
Analysis 1.3. Comparison 1 Oral glutamine versus oral placebo studies, Outcome 3 Number of patients who developed
line infections from start to end of study.. . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 1.4. Comparison 1 Oral glutamine versus oral placebo studies, Outcome 4 Difference in mean % change in body
weight from start to end of the study between the trial groups.. . . . . . . . . . . . . . . . . .
Analysis 1.5. Comparison 1 Oral glutamine versus oral placebo studies, Outcome 5 Mean duration (+/-SD) that nutritional
intervention is given as PN.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 1.6. Comparison 1 Oral glutamine versus oral placebo studies, Outcome 6 Number of patients who developed >
grade 2 graft versus host disease (GVHD).. . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 1.7. Comparison 1 Oral glutamine versus oral placebo studies, Outcome 7 Number of days(+/-SD) to achieve
normal neutrophil level (>0.5 X 10/9/l) after day 0 of BMT.. . . . . . . . . . . . . . . . . .
Analysis 1.8. Comparison 1 Oral glutamine versus oral placebo studies, Outcome 8 Actual numbers of patients who have
completed the study and survived to the 100th day post BMT.. . . . . . . . . . . . . . . . . .
Analysis 1.9. Comparison 1 Oral glutamine versus oral placebo studies, Outcome 9 Actual number of patients who have
completed the study and survived beyond day 100 post BMT.. . . . . . . . . . . . . . . . . .
Analysis 1.10. Comparison 1 Oral glutamine versus oral placebo studies, Outcome 10 Number with positive blood
cultures. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 2.1. Comparison 2 PN + glutamine versus standard PN, Outcome 1 Mean duration(+/-SD) of time in hospital
(e.g. admission to discharge or from day 0 to discharge home).. . . . . . . . . . . . . . . . . .
Analysis 2.2. Comparison 2 PN + glutamine versus standard PN, Outcome 2 Mean(+/-SD) cumulative mucositis score.
Analysis 2.3. Comparison 2 PN + glutamine versus standard PN, Outcome 3 Number of patients who developed line
infections from start to end of study.. . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 2.4. Comparison 2 PN + glutamine versus standard PN, Outcome 4 Difference in mean % change in body weight
from start to end of the study between the trial groups.. . . . . . . . . . . . . . . . . . . .
Analysis 2.5. Comparison 2 PN + glutamine versus standard PN, Outcome 5 Mean duration (+/-SD) that nutritional
intervention is given.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 2.6. Comparison 2 PN + glutamine versus standard PN, Outcome 6 Number of patients who developed >/=grade
2 graft versus host disease (GVHD).. . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 2.7. Comparison 2 PN + glutamine versus standard PN, Outcome 7 Number of days(+/-SD) to achieve normal
neutrophil level (>0.5 X 10/9/l) after day 0 of BMT.. . . . . . . . . . . . . . . . . . . . .
Analysis 2.8. Comparison 2 PN + glutamine versus standard PN, Outcome 8 Actual numbers of patients who have
completed the study and survived to the 100th day post BMT.. . . . . . . . . . . . . . . . . .
Analysis 2.9. Comparison 2 PN + glutamine versus standard PN, Outcome 9 Number of patients with positive blood
cultures. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1
1
2
2
3
3
4
6
7
7
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11
33
37
38
39
40
41
42
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44
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46
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i
Analysis 3.1. Comparison 3 PN vs IV hydration, Outcome 1 Mean duration (+/-SD) of time in hospital (e.g. from discharge
admission to discharge or day 0 to discharge).. . . . . . . . . . . . . . . . . . . . . . .
Analysis 3.2. Comparison 3 PN vs IV hydration, Outcome 2 Mean(+/-SD) number of days patients had some degree of
mucositis from start to end of study.. . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 3.3. Comparison 3 PN vs IV hydration, Outcome 3 Number of patients who developed line infections from start
to end of study.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 3.4. Comparison 3 PN vs IV hydration, Outcome 4 Difference in mean % change in body weight from start to
end of the study between the trial groups.. . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 3.5. Comparison 3 PN vs IV hydration, Outcome 5 Mean duration (+/-SD) that nutritional intervention is
given.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 3.6. Comparison 3 PN vs IV hydration, Outcome 6 Number of patients who developed > grade 2 graft versus host
disease (GVHD).. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 3.7. Comparison 3 PN vs IV hydration, Outcome 7 Number of days(+/-SD) to achieve normal neutrophil level
(>0.5 X 10/9/l) after day 0 of BMT.. . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 3.8. Comparison 3 PN vs IV hydration, Outcome 8 Actual numbers of patients who have completed the study
and survived to the 100th day post BMT.. . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 3.9. Comparison 3 PN vs IV hydration, Outcome 9 Actual number of patients who survived to day 200 post
BMT.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 3.10. Comparison 3 PN vs IV hydration, Outcome 10 Mean % change in albumin. . . . . . . . . .
Analysis 4.1. Comparison 4 PN vs enteral feeding studies, Outcome 1 Mean duration (+/-SD) of time in hospital (e.g. from
admission to discharge or day 0 to discharge).. . . . . . . . . . . . . . . . . . . . . . .
Analysis 4.2. Comparison 4 PN vs enteral feeding studies, Outcome 2 Mean(+/-SD) number of days patients had some
degree of mucositis from start to end of study.. . . . . . . . . . . . . . . . . . . . . . .
Analysis 4.3. Comparison 4 PN vs enteral feeding studies, Outcome 3 Number of patients who developed line infections
from start to end of study.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 4.4. Comparison 4 PN vs enteral feeding studies, Outcome 4 Difference in mean % change in body weight from
start to end of the study between the trial groups.. . . . . . . . . . . . . . . . . . . . . .
Analysis 4.5. Comparison 4 PN vs enteral feeding studies, Outcome 5 Mean duration (+/-SD) that nutritional intervention
is given..
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 4.6. Comparison 4 PN vs enteral feeding studies, Outcome 6 Number of patients who developed > grade 2 graft
versus host disease (GVHD).. . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 4.7. Comparison 4 PN vs enteral feeding studies, Outcome 7 Number of days(+/-SD) to achieve normal neutrophil
level (>0.5 X 10/9/l) after day 0 of BMT.. . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 4.8. Comparison 4 PN vs enteral feeding studies, Outcome 8 Actual numbers of patients who have completed the
study and survived to the 100th day post BMT.. . . . . . . . . . . . . . . . . . . . . . .
Analysis 4.9. Comparison 4 PN vs enteral feeding studies, Outcome 9 Actual number of patients who have completed the
study and survived beyond day 200 post BMT.. . . . . . . . . . . . . . . . . . . . . . .
Analysis 5.1. Comparison 5 Oral eicosapentaenoic acid supplementation versus nil, Outcome 1 Numbers not developing
graft versus host disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
ADDITIONAL TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
FEEDBACK . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
WHATS NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
NOTES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
INDEX TERMS
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55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
73
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[Intervention Review]

Susan M Murray1 , Sima Pindoria2
1 Royal College of Physicians, London, UK. 2 Centre for Paediatric Epidemiology and Biostatistics, Institute of Child Health, London,
UK
Contact address: Susan M Murray, Royal College of Physicians, London, UK. suzdmurray@aol.com.
Editorial group: Cochrane Pain, Palliative and Supportive Care Group.
Publication status and date: Edited (no change to conclusions), published in Issue 5, 2014.
Review content assessed as up-to-date: 30 April 2008.
Citation: Murray SM, Pindoria S. Nutrition support for bone marrow transplant patients. Cochrane Database of Systematic Reviews
2009, Issue 1. Art. No.: CD002920. DOI: 10.1002/14651858.CD002920.pub3.
ABSTRACT
Background
This is an update of the original Cochrane review published in Issue 2, 2002. Bone marrow transplantation involves administration of
toxic chemotherapy and infusion of marrow cells. After treatment, patients can develop poor appetite, mucositis and gastrointestinal
failure, leading to malnutrition. To prevent this, parenteral nutrition (PN) support is often first choice but is associated with increased
risk of infection. Enteral nutrition (EN) is an alternative, as is addition of substrates.
Objectives
To determine efficacy of EN or PN support for patients receiving bone marrow transplant.
Search methods
Search of The Cochrane Library, MEDLINE, EMBASE and CINAHL in November 2000 and subsequently June 2006.
Selection criteria
RCTs that compared one form of nutrition support with another, or control, for bone marrow transplant patients.
Data collection and analysis
Twenty nine studies were identified. Data were collected on participants characteristics; adverse effects; neutropaenia; % change in
body weight; graft versus host disease; and survival.
Main results
In two studies (82 participants) glutamine mouthwash reduced number of days patients were neutropenic (6.82 days, 95%CI (1.67
to 11.98) P = 0.009) compared with placebo. Three studies reported (103 participants) that patients receiving PN with glutamine had
reduced hospital stay, 6.62 d (95%CI 3.47 to 9.77, P = 0.00004) compared with patients receiving standard PN. However, in the
update a further study was added (147 participants) which altered the pooled results: duration in hospital may be increased for those
who receive PN with additional glutamine - 0.22 days (95%CI (1.29 to 1.72). Two other studies reported that (73 participants) patients
receiving PN plus glutamine had reduced incidence of positive blood cultures (OR 0.23, 95%CI 0.08 to 0.65, P = 0.006) compared to
those receiving standard PN. However, a study from the update (113 participants in total) showed the odds of having a positive blood
culture have increased but are still less likely if the patient receives PN with glutamine compared to standard PN (OR 0.46, 95%CI
0.20 to 1.04). When patients were given PN versus IV hydration, (25 participants) patients receiving PN had a higher incidence of
line infections (OR 21.23, 95%CI 4.15 to 108.73, P = 0.0002) compared to those receiving standard IV fluids. The update identified
one study which recognised that (55 participants) those who received IV were likely to spend less time in hospital, 3.30 days (95%CI
-0.38 to 6.98, P = 0.08), although this result was not significant. As reported in the original review there remains no evaluable data to
properly compare PN with EN.
Authors conclusions
In this update an additional study that compared PN and Glutamine versus standard PN showed that the certain benefits of parenteral
nutrition with added glutamine compared to standard PN for reducing hospital stay are no longer definite. When PN with glutamine
is compared with standard PN, patients may not leave hospital earlier, but do have reduced incidence of positive blood cultures, than
those receiving standard PN. Where possible use of intravenous fluids and oral diet should be considered as a preference to parenteral
nutrition, however, in the event of a patient suffering severe gastrointestinal failure even with a trial of enteral feeding, PN with the
addition of glutamine could be considered.
PLAIN LANGUAGE SUMMARY

Nutritional support for patients who have had a bone marrow transplant
Bone marrow transplant patients can experience prolonged poor appetite with vomiting and diarrhoea. Malnutrition is a consequence.
To prevent this, patients can receive nutritious fluids orally or via a nasogastric tube, or intravenously as parenteral nutrition. The
benefits of either route are unclear. Studies were found that compared these interventions but missing data prevents proper assessment
of the benefits. However, the limited data available indicates that when patients undergo bone marrow transplantation and are given
intravenous fluids and are encouraged to have an oral diet they are less likely to experience infections and are more likely to go home
earlier than if they are given standard parenteral nutrition routinely. In the event that patients nutritional intake is inadequate because
of an inadequate oral intake or because they are unable to tolerate tube feeding and are given parenteral nutrition with added glutamine
they are likely to have less infections but may not necessarily leave hospital earlier.
BACKGROUND
Patients receiving bone marrow transplantation (BMT) for malignant and non malignant diseases are prone to varying degrees of
gastrointestinal failure. The main symptoms are prolonged vomiting, diarrhoea and at worst but rarely, intestinal obstruction. The
cause of gastrointestinal failure is unclear but BMT patients in
addition to receiving chemotherapy, which is toxic to the gut and
destroys the hosts marrow cells, receive either donor marrow cells
(allogeneic) or their own marrow cells (autologous). The receipt
of marrow increases the potential complication of graft versus host
disease and infection which can magnify the difficulties in the
nutritional management of these patients. Many patients experience a significant reduction in appetite and therefore calorie intake
within a few days of admission to hospital which is frequently associated with a significant decrease in body weight. Consequently
optimum delivery of nutrition support often becomes essential
early on in the course of treatment for a BMT.
Traditionally, parenteral nutrition (PN), which is the administration of intravenous nutrition given to bypass the alimentary
canal when it is not functioning adequately, has been given as
the first option of nutrition support to BMT patients (Weisdorf

1984; Herrmann 1993). This is in preference to enteral nutrition
(EN) which is the delivery of oral or tube feeding via any route
connected to the gastrointestinal tract. The reasons for this are
probably because routine insertion of long lines has enabled PN
to be delivered relatively effortlessly and also because there was a
belief that enteral feeding is an unacceptable form of force feeding (Rickard 1980) and may not be well tolerated. The advantages of either of these types of nutrition support in BMT patients
are not clear but PN is associated with more complications e.g.
increased line infections and reduction in gut mucosal integrity
(Kudsk 1994) which may lead to longer hospitalisation. There are
some reports from prospective studies, on the successes of enteral
feeding in these types of patients (Papadopoulou 1997). Several
authors would now argue that enteral feeding should always be
considered as the first option of nutrition support for these patients
(Mercadante 1998a; Iestra 1999). However, there have been few
attempts from prospective randomised controlled trials to prove
the benefits of enteral or parenteral nutrition support for BMT
patients.

Two authors, Lipman 1991b and Klein 1994, have previously, independently, reviewed the efficacy of nutrition support in cancer
patients. Both authors examined controlled trials of various forms
of nutrition support in a variety of patients receiving therapy for
cancer and BMT. They reported that nutrition support did not
appear to consistently improve nutritional parameters and was
not clinically effective in improving other important outcomes
for cancer patients. However, there was some evidence from two
randomised controlled trials (RCTs) (Szeluga 1987 and Weisdorf
1987) that BMT patients, survival rate improved when given PN
but infection rates and costs were higher for those receiving PN
compared to those receiving EN. Both of these reviews have been
assessed by peer reviewers from the Centre for Reviews and Dissemination, York, UK, (reviews on The Cochrane Library). They
commented that, whilst the conclusions of these reviews may reflect the benefits of nutrition support for patients receiving treatment for cancer, they were unable to determine the completeness
of the reviews because they did not satisfy the methodological criteria that has been proposed for scientific overviews.
Since then, and in the last decade, there has been increasing interest in the addition of glutamine to both enteral and parenteral solutions. Glutamine is considered to be a non-essential amino acid
which may become an essential amino acid for the catabolic sick
patient. It may also have an affect on preventing gut atrophy and
also enhance immune function (Sax 1992), both of which are potentially debilitating problems for BMT patients. As a result there
have been an increasing number of controlled and uncontrolled
trials reporting the benefits of glutamine in BMT patients.
Since the treatment for BMT patients differs significantly from
cancer patients because of the receipt of marrow cells, this review
(unlike Lipman 1991b and Klein 1994) has focused specifically
on BMT patients. The aim is to assess the effectiveness of any type
of feeding regime that has been compared in patients receiving
BMT.
OBJECTIVES
To determine the efficacy of any form of enteral or parenteral nutrition support given to patients receiving bone marrow transplantation. Efficacy will be considered in terms of time in hospital,
complications, change in nutritional status e.g. change in body
weight, and survival.
METHODS
Criteria for considering studies for this review
Types of studies
Any randomised (strict format of patient allocation to experimental group e.g. centralised randomisation) or quasi randomised (e.g.
alternate patient admissions) controlled trial.
Types of participants
Participants of all ages receiving any type of bone marrow transplant.
Types of interventions
RCTs comparing one type or mode of nutrition support (enteral
or parenteral) with another or with an intravenous solution of
glucose/saline. Where enteral nutrition (EN) is the delivery of any
substance of nutritional value in solid or liquid form (and can
include usual food intake) that passes any part of the digestive tract,
regardless of the method of delivery e.g. orally or via a tube (e.g.
nasogastric, gastrostomy, jejunostomy). Parenteral nutrition (PN)
is the administration of nutritional liquids containing a minimum
of glucose and amino acids which is administered through the
central or peripheral venous system and therefore bypasses the
gastrointestinal tract.
Types of outcome measures

Defined outcome measures considered most important are listed
below.
Primary outcomes
Hospital duration e.g. mean duration admission to

discharge or from day 0 to discharge home.
Mucositis - mean number of days patient groups had some
degree of mucositis from start to end of study.
GVHD - number of patients who developed > grade 2 graft
versus host disease (GVHD).
Nutritional status -difference in mean % change in body
weight from start to end of study between the trial groups.
Duration of nutritional intervention/time to resume
adequate oral intake.
Neutropaenia mean number of days to achieve normal
neutrophil level after day of BMT, day 0.
Line infection - number of patients who developed line
infections from start to the end of the study.
Number with positive blood cultures.
Survival to 100 day - actual numbers who have completed
study surviving to the 100th day post-BMT.
Survival beyond 100 days - actual numbers who have
completed study surviving beyond day 100 or two year survival.

Secondary outcomes
Vomiting - mean number of days patients had >/= than 3

vomits/day from start to end of study.
Diarrhoea - mean number of days patients had >/= 3 bowel
motions /day from start to end of study.
Veno Occlusive Disease - number of patients who developed
veno occlusive disease (VOD) actual number/per group.
Liver function disturbances - number of patients who had
an abnormal bilirubin level from the start of study to end of
study.
Hepatomegaly - number of patients who developed
hepatomegaly from start to end of study.
Albumin - mean change in albumin from start to end of
study between the trial groups.
Pre-Albumin - mean change in pre-albumin from start to
end of study between the trial groups.
Engraftment - mean duration for each group to achieve
engraftment, post-BMT (from day 0).
Search methods for identification of studies

Studies were identified by searching The Cochrane Library (Issue
4, 2000, subsequent search Issue 2, 2006), MEDLINE (1966 to
2000, subsequent search June 2006), EMBASE (1988 to 2000,
subsequent search June 2006) and CINAHL (1982 to 2000, subsequent search June 2006). An example of the search strategy used
and adapted for all databases searched can be seen in Appendix 1.
Reference lists of identified trials and conference proceedings were
also searched for relevant studies.
A search strategy (with no randomised controlled trial (RCT)
filter) was designed for identifying trials from the following
databases: The Cochrane Library, MEDLINE, EMBASE and
CINAHL.
Hand searching included nutrition and bone marrow transplant
conference proceedings, reference lists of papers found through
electronic searching, and consultation with experts.
Data collection and analysis
Study selection
Studies identified by the computerised search were scanned by
the lead review author and all apparently relevant studies were
retrieved. These were assessed independently by the lead review
author (SM) and co-author (SP) for inclusion or exclusion in the
review according to the pre-specified inclusion criteria. A data extraction form was designed and used to record data on participants, interventions and outcomes as described in the Criteria
for considering studies for this review section above. Differences
between review authors extracted results were resolved by discussion.
Correspondence with authors

Many of the authors of included studies either did not report all
of the desired outcomes of interest or presented them in a format
unsuitable for meta-analysis. Where it was possible to locate the
authors of the main studies, a standard letter requesting further
information was sent.
Statistical methods
Outcomes measured as continuous data (time in hospital, change
in nutritional status) were analysed using means and mean differences with their corresponding standard deviations and standard errors, and reported with 95% confidence intervals (CIs).
Dichotomous data were analysed using odds ratios and reported
with 95% CIs. Where meta-analyses were possible, summary estimates of measures of relevant outcomes with 95% CIs were reported using a fixed-effect model.
Statistical heterogeneity was tested using a Chi square test. Where
the P value was less than or equal to 0.05 this indicated significant
heterogeneity, and If this is the case a random effects model will
be used to derive a summary statistic with 95% CIs.
It was planned to investigate clinical heterogeneity by performing
analyses on the following sub-groups: adults versus children (0 to
18 years); disease type; transplant type. However, insufficient data
were available.
Similarly, there were insufficient data to:
assess the effect of the type of allocation concealment;
assess the effect of loss to follow-up;
calculate a number needed to treat to benefit (NNT).
RESULTS
Description of studies
In the first review thirty five studies were identified of which 11
were excluded. Two review authors extracted data from 24 studies
which fulfilled all the inclusion criteria; 16 were allocated to four
interventions: oral glutamine versus placebo; PN and glutamine
versus standard PN; PN versus IV hydration; PN versus EN. Eight
other studies compared a variety of other interventions that could
not be grouped. The details of trials in each group are listed below.
For the update of this review 17 studies were identified, 12 were
excluded and five were included. Three of the five included studies
were allocated to either oral glutamine versus placebo (1); PN and
glutamine versus standard PN (1); PN versus IV hydration (1).

Two other studies were separate interventions and could not be

grouped.
Consequently in this review there are 29 included studies -19 studies have been allocated to four main types of nutritional interventions and ten studies remain ungrouped since they individually
assess other types of interventions.
Data were collected on participants characteristics; adverse effects;
neutropaenia; % change in body weight; graft versus host disease;
and survival.
Oral glutamine versus placebo
Following the original review when there were four studies, one
further study Aquino 2005 was identified in the update. The five
trials (Aquino 2005; Coghlin Dickson 2000; Jebb 1995; Schloerb
1999) compare oral glutamine versus placebo and include 463
participants. In one trial by Schloerb 1999, participants failing to
take the oral supplement were given either PN with glutamine
or standard PN according to which group the participants were
originally randomised. Despite this, the results of this study were
allocated to this group because the original allocation was to oral
glutamine or placebo.
Parenteral nutrition with glutamine versus standard
parenteral nutrition
In the original review there were seven publications of trials comparing PN with glutamine versus standard PN. Four of these were
duplicate reports of one original study by Ziegler 1992. They were
MacBurney 1994; Scheltinga 1991; Ziegler 1998; Young 1993.
Data from studies by Ziegler 1992; Brown 1998; Schloerb 1993
were used. For the update of this review another study Pytlik 2002
was found and merged with the data from the three studies previously mentioned, totaling 148 participants.
Standard parenteral nutrition versus intravenous
hydration
Two trials involving a total of 166 participants were identified in
the first review (Lough 1990; Weisdorf 1987). A further study
Roberts 2003a was identified in the update and has been merged
with these studies. The total number of participants in this group
of studies is 221.
The other eight trials identified in the first review (Aldamiz 1996;
Charuhas 1997; Jimenez 1999; Lenssen 1987; Lenssen 1998;
Malhotra 1996; Mulder 1989; Muscaritoli 1998) and two others in
the update (Santos 2001; Takatsuka 2002) compared a miscellany
of nutritional interventions, and could not be allocated to the
above groups.
Risk of bias in included studies

Three aspects of study methodology were addressed:
allocation concealment (Mulrow 1997);
blinding (although this was not considered to be a real
threat to biasing the results since the main outcomes were
considered to be objective measures);
loss to follow up.
The details of these can be viewed in Additional Table 1.
Effects of interventions
Although five additional studies were added to the update of this
review many of the outcomes in these studies could not be included in the data analysis since they were either presented in heterogenous units or were not relevant to the objectives of this review.
The results of the four main groups of comparisons of nutrition
support are listed below.
Oral glutamine versus oral placebo
For a number of the main outcomes adequate data were provided
by Jebb 1995 and Schloerb 1999 only.
The use of an oral placebo mouth wash, resulted in a significant
reduction in days to achieve a normal neutrophil level (6.82 days,
95% CI (1.67 to 11.98) P = 0.009) compared to an oral glutamine
mouth wash.
The results for hospital duration, change in body weight, duration
of nutritional intervention, numbers with positive blood cultures
were not significant and also remained not significant when the
additional data retrieved in the update of this review from Aquino
2005 for survival at 100 days was added.
PN and glutamine versus standard PN
Parenteral nutrition versus enteral nutrition

In the first review one full report and two abstracts (Cope 1997;
Szeluga 1987; Young 1997), including a total of 144 participants,
were identified. During the update of this review one other study
comparing PN versus EN (Hopman 2003) was found but the
outcome data could not be used since it appeared that some of
the outcome data was obtained from participants who were not
randomised into the study.
In the first review data was provided by either two or all three authors on all the main outcomes of interest except line infections.
For the update, outcome data from the study reported by Pytlik
2002 for hospital duration, mean cumulative mucositis score, duration that nutritional intervention (PN) was given and numbers
of participants with positive blood cultures were added. In the
first review one of the most significant outcomes was that, for participants receiving glutamine enriched PN, hospital duration was

reduced by 6.62 days (weighted mean difference) with 95% CI

-9.77 to 3.47, P = 0.00004. However, with the addition of the
data from Pytlik 2002 it appears that the possibility that PN with
added glutamine could reduce hospital admission is no longer apparent since the pooled result suggests that participants given PN
with Glutamine (although not significant) have an increase of 0.22
days in hospital with 95% CI -1.29 to 1.72, P = 0.78 compared
with participants given standard PN. Despite the additional data
added in from Pytlik 2002 the likelihood of these participants developing positive blood cultures remains less compared to those
on standard PN, although this is not significant. The odds ratio is
0.46 with a 95% CI 0.20 to 1.04, P = 0.06.
For the first review and with this update no significant difference
was found in the treatment affect for either PN and glutamine or
standard PN for severity of mucositis, change in body weight, duration parenteral nutrition required, incidence of > grade 2 GVHD,
duration of neutropaenia and survival at 100 days.
PN versus IV hydration
Like the first review Lough 1990; Weisdorf 1987 and now Roberts
2003a considered a number of similar outcomes, however a number of the outcomes within these studies are expressed in a variety
of different units that has not always made it possible to pool all the
outcomes of interest into a meta-analysis. In the first review Lough
1990 provided data on a number of outcomes of interest, some
showing significant differences between the PN and IV hydration
group. His data showed that the odds of having a line infection
when given PN compared to IV hydration were 21.23 than for
participants receiving IV hydration (95% CI 4.15 to 108.73, P
= 0.0002). Also, the mean percentage change in albumin for the
IV hydration group showed surprisingly significant increases in
albumin concentrations compared to the PN group and this was
also found with in the study by Roberts 2003a. (The pooled mean
difference was -3.72 (95% CI -5.96 to -1.49), P = 0.001). Lough
1990 also indicated that for percentage change in body weight
PN was more beneficial than IV hydration for preventing weight
loss and this was also identified in the study by Roberts 2003a.
The weighted mean difference for percentage change in weight
in the first review was 2.76 (95% CI 1.26 to 4.26, P = 0.0003)
and with the additional data from Roberts 2003A the weighted
mean difference was 2.81 (95%CI 1.34 to -4.29). There was no
significant difference in survival at 200 days post BMT. Lough
1990 showed that the odds of surviving this long post BMT were
2.10 (95%CI 0.48 to 9.18, P = 0.3) favouring PN over IV hydration (29 participants). Roberts 2003a provided data on survival at
two years post BMT and five years post BMT but this could not
be merged with the survival data provided by Lough 1990 since
it was estimated at different time points. The data from Roberts
2003a showed that the probability of survival at two years was
higher for the participants who received PN, 74%, compared to
57% for those who were in the group randomised to receive oral
diet and or intravenous hydration. However at 5 years post BMT

the probability of survival in either the PN or the oral diet/IV
hydration group was the same at 38%.
PN versus EN
For the update of this review one other RCT (Hopman 2003) was
found but could not be included since the outcome data included
data from participants who were not originally randomised into
the study. No further studies were included for this part. Therefore the findings reported in the first review remain that for the
three studies originally reported, a number of outcomes of interest were presented but none of the data could be utilised. Data
provided by Szeluga 1987 on change in body weight indicated
that participants receiving parenteral nutrition were more likely
to gain weight with this form of nutrition support. However, the
crossover of participants from one group to another during the
study provided uncertainty on the clarity of the data presented
in the paper. Young 1997 presented similar data as median and
ranges, which could not be utilised but also favoured parenteral
nutrition for maintaining body weight, although the results were
not significant. All three authors (Cope 1997, Szeluga 1987 and
Young 1997) reported measuring hospital duration but the data
were inadequate for analysis.
Cope 1997 and Young 1997 both suggested that length of hospitalisation was significantly shorter in the enteral feeding group,
whilst Szeluga 1987 implied that there was no significant difference between either group.
Since all the other included studies could not be grouped and had
low power, no comprehensive assessment of the results could be
made. If future randomised controlled trials of studies of these
interventions are performed, it may then be possible to group some
of the outcomes.
DISCUSSION
This review had wider inclusion criteria than those on nutrition
support and cancer by Lipman 1991b and Klein 1994, but included only BMT patients. The identification of 24 RCTs in the
first review and now a further five in the update of this review
suggests there is a keen interest in identifying the best mode of
nutrition support for BMT patients.
In the first review we reported that for oral glutamine versus oral
placebo trials, data from two out of four studies only could be
used. This reduced the pooled sample size significantly. Most of
the results were inconclusive for the outcomes of interest. One of
the authors of a trial with no usable data (Coghlin Dickson 2000)
concluded that the benefits of oral glutamine were inconclusive
and that further trials are required. In the first review we suggested
that since the studies of Coghlin Dickson 2000 and Anderson

1998 included 251 participants, it would have been beneficial if the

missing data from these studies could be retrieved to increase the
pooled sample size and improve the reliability of detecting a true
affect of the intervention, before further studies are performed. For
the update of this review one further study by Aquino 2005 which
included children (whose mean age ranged from 9-10 years) has
been added to this group of studies and whilst there is interesting
data provided most of this could not be pooled with the exception
of one outcome - survival to the 100th day. For this it appears
that the children who received the placebo were more likely to
survive to the 100th day post BMT than those who received the
intervention but this result and the overall pooled result is not
significant.
In the first review for the PN and glutamine versus standard PN
trials, we commented on the positive effect that PN with Glutamine had on reducing the incidence of positive blood cultures
and hospital duration. However the addition of data in the second review from Pytlik 2002, with 40 additional participants now
suggests that participants given PN with Glutamine may actually
have an increased hospital duration compared to those given standard PN, although it must be emphasised that this is not significant. However the likelihood that patients will have more positive
blood cultures if they are not given PN with Glutamine remains
consistent but the data for this is also not significant. It would
now seem that the benefits of giving BMT patients who need PN
(because of an inadequate oral intake), PN with Glutamine is not
clear.
For the studies that compared parenteral nutrition versus intravenous hydration and following the update of this review the benefits of PN remain unclear because of insufficient data. The addition of data from Roberts 2003a showed further that patients given
PN are less likely to experience a large decrease in body weight and
hence their nutritional status is perhaps better maintained. Data
on the incidence of line infections remain the same as presented
in the study by Lough 1990 who showed that there was a higher
incidence of line infections associated with parenteral nutrition
compared to the intravenous hydration group, and reminds us that
parenteral nutrition should be administered with caution when
there is evidence of poor tolerance of enteral feed and prolonged
gastrointestinal failure.
In the first review we reported that the results from the parenteral
nutrition versus enteral nutrition trials were inconclusive due to
inadequate data. For the update of this review we identified a
further trial that compared the benefits of PN versus EN, however,
this was excluded because there was not a proper intention to
treat analysis. The authors of these studies have hinted that enteral
nutrition when compared to PN may have an affect on reducing
hospital duration which could have important benefits to patients
as well as cost saving advantages, suggesting the need for a large
randomised controlled trial to compare parenteral nutrition versus
enteral nutrition.
AUTHORS CONCLUSIONS
Implications for practice
Readers of the original review are advised to re-read this update as
the conclusions have changed.
Routine use of parenteral nutrition and glutamine for bone
marrow patients predicted to have prolonged gastrointestinal
failure, could be considered.
Caution in the routine use of PN is still required because of
the increased risk of line infection
Where possible use of intravenous fluids and oral diet
should be considered as a preference to parenteral nutrition,
however, in the event of a patient suffering severe gastrointestinal
failure even with a trial of enteral feeding, PN with the addition
of glutamine could be considered.
Implications for research

For this update 17 more studies were identified in June 2006
and five studies were included. Consequently there are now 29
included studies -19 studies are allocated to four main sub reviews
and ten studies remain ungrouped. To conclude:
The benefits of oral glutamine mouth washes compared to
oral placebo remain unclear and further studies or the provision
of complete data from the studies already performed are required.
The benefits of glutamine in PN compared to standard PN
are now not certain.
For patients who receive PN and glutamine there no longer
appears to be a reduction in hospital stay, but they may have a
reduced incidence of positive blood cultures.
The benefits of enteral nutrition in preference to PN are
still not clear, reflecting an urgent need for a good quality
prospective RCTs in this area.
ACKNOWLEDGEMENTS
Systematic Reviews Training Unit at the Institute of Child
Health, London for providing Susan Murray with funding to
undertake training in systematic reviews.

Professor PR Schloerb and Dr CH Poynton kindly

provided unpublished data for this review.
I acknowledge Peter Katz input in updating the search
strategy for the updated review who is sadly now deceased.
REFERENCES
References to studies included in this review

Aldamiz 1996 {published data only}
Aldamiz EL, Bachiller MP, Ariz MC, Gimenez A, Barcia
MJ, Marin M. Continuous versus cyclic parenteral nutrition
during bone marrow transplantation: Assessment and
follow-up. Clinical Nutrition 1996;15(6):3336.
Anderson 1998 {published data only}
Anderson PM, Ramsay NK, Shu XO, Rydholm N,
Rogosheske J, Nicklow R, et al.Effect of low-dose oral
glutamine on painful stomatitis during bone marrow
transplantation. Bone Marrow Transplant 1998;22(4):
33944. [: 1]
Aquino 2005 {published data only}
VM Aquino, AR Harvey, JH Garvin, KT Godder, ML

Nieder, RH Adams, et al.A double blind randomized
placebo-controlled study of oral glutamine in the prevention
of mucositis in children undergoing hematopoietic stem cell
transplantation: a pediatric blood and marrow transplant
consortium study. Bone Marrow Transplantation 2005;36:
6116.
Brown 1998 {published data only}
Brown SA, Goringe A, Fegan C, Davies SV, Giddings J,
Whittaker JA, et al.Parenteral glutamine protects hepatic
function during bone marrow transplantation. Bone
Marrow Transplant 1998;22(3):2814.
Charuhas 1997 {published data only}
Charuhas PM, Fosberg KL, Bruemmer B, Aker SN,
Leisenring W, Seidel K, Sullivan KM. A double-blind
randomized trial comparing outpatient parenteral nutrition
with intravenous hydration: effect on resumption of oral
intake after marrow transplantation. Journal of Parenteral
and Enteral Nutrition 1997;21(3):15761.
Coghlin Dickson 2000 {published data only}
Coghlin Dickson T, Wong RM, Negrin RS, Shizuru
JA, Johnston LJ, Hu WW, et al.Effect of oral glutamine
supplementation during bone marrow transplantation.
Journal of Parenteral and Enteral Nutrition 2000;24(2):616.
Cope 1997 {published data only}
Cope FO. Prophylactic enteral support to BMT patients
reduces length of hospital stay, improves GI integrity and
nutritional status, and reduces intake requirements required
for positive outcome. Procedures of the Annual Meeting of
the American Society for Clinical Oncology. 1997.
Jebb 1995 {published data only}

Jebb SA, Marcus R, Elia M. A pilot study of oral glutamine
supplementation in patients receiving bone marrow
transplants. Clinical Nutrition 1995;14(3):1625.
Jimenez 1999 {published data only}
Jimenez JF, Ortiz LC, Garcia GJ, Garnacho MJ, Rodriguez
FJ, Espigado TI. Prospective, comparative study of different
amino acid and lipid solutions in the parenteral nutrition
of patients subjected to a bone marrow transplantation.
Nutricion Hospitalaria 1999;14(2):5766.
Lenssen 1987 {published data only}
Lenssen P, Cheney CL, Aker SN, Cunningham BA,
Darbinian J, Gauvreau JM, Barale KV. Intravenous
branched chain amino acid trial in marrow transplant
recipients. Journal of Parenteral and Enteral Nutrition 1987;
11(2):1128.
Lenssen 1998 {published data only}
Lenssen P, Bruemmer BA, Bowden RA, Gooley T, Aker
SN, Mattson D. Intravenous lipid dose and incidence of
bacteremia and fungemia in patients undergoing bone
marrow transplantation. American Journal of Clinical
Nutrition 1998;67(5):92733.
Lough 1990 {published data only}
Lough M, Watkins R, Campbell M, Carr K, Burnett
A, Shenkin A. Parenteral nutrition in bone marrow
transplantation. Clinical Nutrition 1990;9(2):97101.
MacBurney 1994 {published data only}
MacBurney M, Young LS, Ziegler TR, Wilmore DW. A
cost-evaluation of glutamine-supplemented parenteral
nutrition in adult bone marrow transplant patients. Journal
of American Dietetics Association 1994;94(11):12636.
Malhotra 1996 {published and unpublished data}
Malhotra D, DeMeo D, Kruger A, Rooney D, Holmes
E, Poe L, et al.Oral elemental nutrition improves
gastrointestinal integrity in patients undergoing bone
marrow transplantation. Proceedings of Asco Vol. 1996;
Vol. 15:450. [: 13]
Mulder 1989 {published data only}
Mulder PO, Bouman JG, Gietema JA, Van Rijsbergen H,
Mulder NH, Van der Geest S, et al.Hyperalimentation in
autologous bone marrow transplantation for solid tumors.
Comparison of total parenteral versus partial parenteral plus
enteral nutrition. Cancer 1989;64(10):204552.
Muscaritoli 1998 {published data only}
Muscaritoli M, Conversano L, Torelli GF, Arcese W,
Capria S, Cangiano C, et al.Clinical and metabolic effects

of different parenteral nutrition regimens in patients

undergoing allogeneic bone marrow transplantation.
Transplantation 1998;66(5):6106.
Pytlik 2002 {published data only}
Pytlik R, Benes P, Patorkova M, Chocenska E, Gregora E,
Prochazka B, et al.Standardised parenteral alanyl-glutamine
dipeptide supplementation is not beneficial in autologous
transplant patients: a randomized, double-blind, placebo
controlled study. Bone Marrow Transplantation 2002;30:
953961.
Roberts 2003a {published data only}
Roberts S, Miller J, Pineiro L, Jennings L. Total parenteral

nutrition vs oral diet in autologous hematopoietic cell
transplant recipients. Bone Marrow Transplantation 2003;
32:71521.
Santos 2001 {published data only}
Santos P, Lourenco R, Camilo ME, Oliveira AG, Figueira

I, Pereira ME, et al.Parenteral nutrition and cyclosporine:
do lipids make a difference? A prospective randomised cross
over trial. Clinical Nutrition 2001;20(1):3136.
Scheltinga 1991 {published data only}
Scheltinga MR, Young LS, Benfell K, Bye RL, Ziegler TR,
Santos AA, et al.Glutamine-enriched intravenous feedings
attenuate extracellular fluid expansion after a standard stress.
Annals of Surgery 1991;214(4):38595.
Schloerb 1993 {published data only}
Schloerb PR, Amare M. Total parenteral nutrition with
glutamine in bone marrow transplantation and other clinical
applications (a randomized double-blind study). Journal of
Parenteral and Enteral Nutrition 1993;17(5):40713.
Schloerb 1999 {published data only}
Schloerb PR, Skikne BS. Oral and parenteral glutamine in
bone marrow transplantation: a randomized, double-blind
study. Journal of Parenteral and Enteral Nutrition 1999;23
(3):11722.
Journal of Parenteral and Enteral Nutrition 1993;17(5):

4227.
Young 1997 {published and unpublished data}
Young M, Stanford J, Walker DJ, Frost G. Preliminary report
of the efficacy of nasogastric feeding in allogeneic adult bone
marrow transplant patients. Original Communications of
the Nutrition Society Original Communications of the
Nutrition Society 1997. [: 24]
Ziegler 1992 {published data only}
Ziegler TR, Young LS, Benfell K, Scheltinga M, Hortos K,
Bye R, et al.Clinical and metabolic efficacy of glutaminesupplemented parenteral nutrition after bone marrow
transplantation. A randomized, double-blind, controlled
study. Annals of Internal Medicine 1992;116(10):8218.
Ziegler TR, Bye RL, Persinger RL, Young LS, Antin JH,
Wilmore DW. Effects of glutamine supplementation on
circulating lymphocytes after bone marrow transplantation:
a pilot study. American Journal of Medical Sciences 1998;315
(1):410.
References to studies excluded from this review

Clemens 1997 {published data only}
Clemens MR, Waladkhani AR, Bublitz K, Ehninger G,
Gey KF. Supplementation with antioxidants prior to bone
marrow transplantation. Wien Klin Wochenschr 1997;109
(19):7716.
Cohen 1996 {published data only}
Cohen D. Nutrition management of gastrointestinal graftversus-host disease following bone marrow transplantation.
Support Line 1996;5:135.
Duggan 2004 {published data only}
Duggan C, Stark A, Auestad N, Collier S, Fulhan J,
Gura K, et al.Glutamine Supplementation in Infants with
Gastrointestinal Disease: A randomized placebo controlled
pilot trial. Nutrition 2004;20:7526.
Szeluga 1987 {published data only}

Szeluga DJ, Stuart RK, Brookmeyer R, Utermohlen
V, Santos GW. Nutritional support of bone marrow
transplant recipients: a prospective, randomized clinical
trial comparing total parenteral nutrition to an enteral
feeding program. Cancer Research 1987;47(12):330916.
Ford 1992 {published data only}

Ford EG. Clinical comparison of tolerance to elemental
or polymeric enteral feedings in the postoperative patient.
Journal of the American College of Nutrition 1992;11(1):
116.
Takatsuka 2002 {published data only}
Takatsuka H, Takemoto Y, Iwata N, Suehiro A, Hamano

T, Okamoto T, Kanamaru A. Oral eicosapentaenoic acid
for complications of bone marrow transplantation. Bone
Marrow Transplantation 2001;28:76974.
Hopman 2003 {published data only}

Hopman G, Pena E, le Cessie S, van Weel MH, Vossen
JMJJ, Mearin ML. Tube feeding and Bone Marrow
Transplantation. Medical and Paediatric Oncology 2003;40
(6):3759.
Weisdorf 1987 {published data only}

Weisdorf SA, Lysne J, Wind D, Haake RJ, Sharp HL,
Goldman A, et al.Positive effect of prophylactic total
parenteral nutrition on long-term outcome of bone marrow
transplantation. Transplantation 1987;43(6):8338.
Klein 1994 {published data only}

Klein S, Koretz RL. Nutrition support in patients with
cancer: what do the data really show?. Nutrition in Clinical
Practice 1994;9(3):91100.
Young 1993 {published data only}

Young LS, Bye R, Scheltinga M, Ziegler TR, Jacobs DO,
Wilmore DW. Patients receiving glutamine-supplemented
intravenous feedings report an improvement in mood.
Lipman 1991a {published data only}

Lipman TO. Grains or veins: Is enteral nutrition really
better than parenteral nutrition? A look at the evidence.
Journal of Parenteral and Enteral Nutrition 1998;60(22/3):
16782.

Mercadante 1998a {published data only}

Mercadante S. Parenteral versus enteral nutrition in cancer
patients: Indications and practice. Supportive Care in
Cancer 1998;6(2):8593.
Mobrahan 1992 {published data only}
Mobrahan S. Glutamine: A conditionally essential nutrient
or another nutritional puzzle. Nutrition Reviews 1992;50
(11):3313.
Piccirillo 2002 {published data only}
Piccirillo N, S De Matteis L, Laurenti P, Chiusolo F, Sora
S, Rutella S, et al.Glutmine enriched parenteral nutrition
after autologous peripheral blood stem cell transplantation:
effects on immune reconstitution and mucositis. Bone
Marrow Transplantation 2002;29:Suppl S 21.
Piccirillo 2004 {published data only}
N Piccirillo, S De Matteis, F Sora, L Laurenti, P Chiusolo,
G Leone, S Sica. Glutamine parenteral supplementation in
stem cell transplant. Bone Marrow Transplantation 2004.
Poznarova 2003 {published data only}
Poznarova A, Horacek J, Zac P, Kmonicek M, Maly J. A
randomised double blind comparative study of parenteral
nutritional support with or without glutamine in autologous
stem cell transplantation for hematologic malignancies.
Bone Marrow Transplantation. 2003; Vol. 31 (Suppl 1):
S21920.
Pytilik 2002a {published data only}
Pytilik R, Benes P, Gregora E, Pajorkova M, Chocenska
E, Prochazka B, et al.No role for parenteral glutamine
supplementation in autologous stem cell transplant
patients: results of a triple blinded study. Bone Marrow
Transplantation. 2002; Vol. 29 (Suppl2):S20.
Pytilik 2002b {published data only}
Pytilik R, Benes P, Patorkova M, Chocenska E, Gregora E,
Prochazka B, et al.Standardised Parenteral alanyl glutamine
dipeptide supplementation is not beneficial in autologous
transplant patients: a randomised, double blind, placebo
controlled study.. Bone Marrow Transplantation 2002;30
(12):95361.
Ramsay 1981 {published data only}
Ramsay N. Prevention of graft versus host disease (GVHD)
in bone marrow transplantation (BMT) recipients: A
randomized study. Procedures of the American Association
of Cancer Research. 1981.
Reiffers 1996 {published data only}
Reiffers J. Allogeneic vs autologous stem cell transplantation
vs chemotherapy in patients with acute myeloid leukemia
in first remission: the BGMT 87 study. Leukemia 1996;10
(12):187482.
Sax 1992 {published data only}
Sax HC. Clinical and metabolic efficacy of glutaminesupplemented parenteral nutrition after bone marrow
transplantation. A randomized, double-blind, controlled
study. Journal of Parenteral and Enteral Nutrition 1992;16
(6):58990.
Schied 2004 {published data only}

Schied C, Hermann K, Kremer G, Holsing A, Heck G,
Fuchs M, et al.Randomized, double blind, controlled study
of glycl-glutamine-dipeptide in the parenteral nutrition
of patients with acute leukaemia undergoing intensive
chemotherapy. Nutrition 2004;20:24954.
Souba 1993 {published data only}
Souba WW. Total parenteral nutrition with glutamine in
bone marrow transplantation and other clinical applications.
Journal of Parenteral and Enteral Nutrition 1993;17(5):403.
Stern 2000 {published data only}
Jean M Stern, Barbara Bruemmer, Carol M Moinpour,
Keith Sullivan, Polly Lennssen, Saundra Aker. lmpact of a
randomised, controlled trial of liberal versus conservative
hospital discharge criteria on energy, protein and fluid
intake in patients who received marrow transplants. Journal
of the American Dietetic Association 2000;100:101522.
Takatsuka 2001 {published data only}
Takatsuka H, Takemoto Y, Iwata N, Suehiro A, Hamano
T, Kanamaru A, et al.Oral Eicosapentaenoic acid for
complications of bone marrow transplantation. Bone
Marrow Transplantation 2001;28(8):76974.
Thomas R Ziegler. Glutamine Supplementation in Cancer
Patients Receiving Bone Marrow Transplantation and High
Dose Chemotherapy. The Journal of Nutrition September
2001;131(9S):2578S84S.
Ziegler TR. Glutamine supplementation in bone marrow
transplantation. British Journal of Nutrition 2002;87, Suppl
1:S915.
Additional references
Herrmann 1993
Herrmann VM, Petruska PJ. Nutrition support in bone
marrow transplant recipients. Nutritional Clinical Practice
1993;8(1):1927.
Iestra 1999
Iestra JA, Fibbe WE, Zwinderman AH, Romijn JA,
Kromhout D. Parenteral nutrition following intensive
cytotoxic therapy: an exploratory study on the need for
parenteral nutrition after various treatment approaches
for haematological malignancies. Bone Marrow Transplant
1999;23(9):9339.
Kudsk 1994
Kudsk KA. Gut mucosal nutritional support- enteral
nutrition as primary therapy after multiple system trauma.
Gut 1994;suppl 1:S524.
Lipman 1991b
Lipman T. Clinical trials of nutrition support in cancer,
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10
Mulrow 1997
Mulrow CD, Oxman AD, editors. Cochrane Reviewers
Handbook 3.0.2. Oxford: The Cochrane Collaboration,
1997.
Rickard 1980
Rickard KA. Effectiveness of enteral and parenteral nutrition
in the nutritional management of children with Wilms
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Papadopoulou 1997
Papadopoulou A, MacDonald A, Williams MD, Darbyshire
PJ, Booth IW. Enteral nutrition after bone marrow
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Weisdorf 1984
Weisdorf S, Hofland C, Harvey LS, Teasley K, Schissel
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Indicates the major publication for the study

11
CHARACTERISTICS OF STUDIES
Characteristics of included studies [ordered by study ID]

Aldamiz 1996
Methods
Randomised controlled trial

Method of randomisation is not clear.
Participants
24 recruited
BMT type 6 Allogeneic and 18 Autologous BMT patients.
Disease type not specified
Age mean(+/-SD) years:
Continuous PN = 37(+/-9.3)
Cyclical PN = 35.4(+/- 11.1)
Interventions
12 Continuous PN
12 Cyclical PN
Start criteria: Day +1 after BMT
Stop criteria: not clear.
Outcomes
Hospital duration
Change in body weight
Graft versus host disease
Duration of PN
Duration neutropaenia
Notes
There were no losses to follow up.
Risk of bias
Bias
Authors judgement
Support for judgement
Allocation concealment (selection bias)
Unclear risk
B - Unclear
Anderson 1998
Methods
Randomised controlled trial.

Method of randomisation is truly random (computer generated random number list.)
Participants
195 recruited
BMT type: 106 Allogeneic/87 Autologous
Disease type: Haem malignancy 106
Haem disorders 8
Solid tumour 62
Inherited disorders 17
Age (yrs) - mean (range)
Oral Glutamine = 29 (1-62)
Oral Placebo = 27 (1-62)

12
Anderson 1998
(Continued)
Interventions
Randomisation:
98 -Oral mouth rinse glutamine or 1 g/m2, x4/day.
95 - Oral mouth rinse glycine 1g/m2, x4/day
Start criteria: 7 days before BMT
Stop criteria: 28 days after BMT
Outcomes
Mucositis
Survival at day 28 and day 100.
Notes
Follow up:195 recruited, 2 withdrew

98 - Glutamine group ( 2 did not participate)
95 - Control
Risk of bias
Bias
Authors judgement
Low risk
A - Adequate
Aquino 2005
Methods

Method of randomisation was via a random permutation table at a central pharmacy
Participants
120 CHILDREN recruited

BMT type: 106 Allogeneic: 54
Autologous: 66
Disease type: Haem malignancy 64
Solid tumour:48
Haem abnormalities: 10
Age (yrs) - mean
Oral Glutamine =8.9yr
Oral Glycine = 10.5
Interventions
Oral glutamine v Oral glycine 2g/m2 (max 4g/day) dissolved in 500 ml solution administered twice daily
Outcomes
% of doses taken
Hospital days (?units)
Mucositis score
Toxicities
IV narcotic use (days)
PN use (days)
Episodes of bacteraemia
Toxities (including mortality)

13
Aquino 2005
(Continued)
Notes
The study was described as a double blind randomised controlled trial. Method of randomisation was clear but there was no mention on whether the assessors were blind to the
treatment allocation. There were no apparent losses to follow up
Risk of bias
Bias
Authors judgement
Unclear risk
B - Unclear
Brown 1998
Methods

Method of randomisation is truly random
Participants
34 recruited
BMT type: 7 Allogeneic/ 27 Autologous
Disease type: 34 Haem malignancy
Age- years, median (range)
Glutamine = 41(19-62)
Control = 32 (16-55)
Interventions
Randomisation:
18 PN + Glutamine (50 g glutamine/day)
16 to Standard PN (no glutamine)
Start criteria: day -7 before BMT
Stop criteria: on day discharge.
Outcomes

Survival
Notes
Follow up :34 recruited, 8 withdrew.

18- Glutamine group
( four withdrew)
16- Control group ( four withdrew)
Risk of bias
Bias
Authors judgement
Low risk
A - Adequate

14
Charuhas 1997
Methods

Participants
265 BMT (Out patients) recruited

Disease type: 241 Haem malignancy,
2 Haem disorders
12 solid tumour
3 Inherited disorders
Age (range) years:
PN group = 2.7 - 64.2 yrs
IV hydration = 2.1 - 63.1 yrs.
Interventions
Randomisation:
128 PN
130 IV Hydration
Start criteria: at discharge
Stop criteria: oral intake >85% energy requirements, for 3 consecutive days
Outcomes
Hospital readmission
Time to resume oral intake
GVHD
Survival to day 150 (post BMT)
Notes
Risk of bias
Bias
Authors judgement
Unclear risk
B - Unclear
Coghlin Dickson 2000

Methods

Participants
58 recruited
Age (range) years:
Glutamine group:17-58 yrs
Control: 21-59 yrs
Interventions
Randomisation:
29 Oral Glutamine (10 g x 3 doses/day).
29 Placebo (Sucrose, 10 g x 3/day).

15
(Continued)
Outcomes
Hospital duration
Mucositis
Duration of PN
Engraftment
Survival at 2 years
Notes
Risk of bias
Bias
Authors judgement
Unclear risk
B - Unclear
Cope 1997
Methods

Participants
63 recruited
BMT type: not specified
Disease type: not specified
Age - not specified
Interventions
Randomisation:
23 EN
40 PN
Start/Stop criteria:not stated.
Outcomes
Hospital duration
Mucositis
Change in nutritional status
Notes
Loss to follow up is not clear.
Risk of bias
Bias
Authors judgement
Unclear risk
B - Unclear

16
Jebb 1995
Methods

Participants
24 recruited
BMT type: 24 Autologous
Age range not specified.
Interventions
Randomisation:
12 Oral mouth rinse glutamine, 4g x 4/d.
12 Oral mouth rinse polycal, 4g x 4/d.
Start criteria: day +1 after BMT until Stop criteria: mucositis resolved or discharge
Outcomes
Hospital duration
Mucositis
Duration of PN
Duration of neutropaenia
Notes
Follow up: 24 recruited, 8 withdrew.

12- Oral glutamine group ( four withdrew)
12- Control group ( four withdrew)
.
Risk of bias
Bias
Authors judgement
Unclear risk
B - Unclear
Jimenez 1999
Methods

Participants
62 BMT patients.
Interventions
Randomisation:
19 - 22.5% BCAA* + 20%LCT
26 - 45% BCAA* + 20%LCT*
17- 45% BCAA*+ 20%MCT*/ LCT*
Outcomes
Hospital duration
Duration of Mucositis
Duration of PN
Lipid metabolism
Nutritional assessment parameters.
Notes
(Original paper in Spanish)

17
Jimenez 1999
(Continued)
Risk of bias
Bias
Authors judgement
Unclear risk
B - Unclear
Lenssen 1987
Methods

Method of randomisation is truly random.
Participants
40 recruited.
BMT type: 40 Allogeneic
Age median(range) years:
23%BCAA*, PN = 28.5 (18-48)
45% BCAA*, PN = 28.5 (18-49)
Interventions
Randomisation:
20 - 23%BCAA* (PN)
20 - 45% BCAA*(PN)
Start criteria: pre BMT (day not specified)
Stop criteria: oral protein >10g/day.
Outcomes
Notes

20 - 23%BCAA* (PN) (9 withdrew.)
20 - 45% BCAA*(PN) (12 withdrew.)
Risk of bias
Bias
Authors judgement
Low risk
A - Adequate
Lenssen 1998
Methods

Participants
512 recruited.
BMT type: 419 Allogeneic/ 93 Autologous Disease type: 512 Haem malignancy
Age mean + (range) years:
Standard PN Lipid group = 35 (0.5-65)
PN+ low dose lipid group = 35 (0.4 -67).

18
Lenssen 1998
(Continued)
Interventions
Randomisation:
253 Standard PN Lipid
259 Low dose PN Lipid
Start criteria: oral energy intake < basal requirements
Stop criteria: oral energy intake >10kcals/kg/day.
Outcomes
Graft versus host disease.

Death by day 60 and day 150 post BMT.
Notes

253 Standard PN (20 withdrew)
259 Low dose PN Lipid
(23 withdrew)
Risk of bias
Bias
Authors judgement
Unclear risk
B - Unclear
Lough 1990
Methods

Participants
29 recruited.
BMT type: 17 Allogeneic/12 Autologous
Age range (14-44 yrs)
Interventions
Randomisation:
14 PN
15 IV Hydration.
Start criteria: day+1 after BMT until Stop criteria: 15 days after BMT?
Outcomes
Notes
Follow up: 29 randomised,

14 PN (4 excluded from analysis).
15 IV (none excluded)
Risk of bias
Bias
Authors judgement
Low risk
A - Adequate

19
MacBurney 1994
Methods

Participants
43 recruited
Age range: not specified
Interventions
Randomisation:
22 PN+ Glutamine (0.57 g/kg/day
21 Standard PN (no glutamine)
Start criteria: day+1 after BMT
Stop criteria: oral intake > 50% energy requirements for 3 days
Outcomes
Hospital duration
Survival
Notes
Small sub report from Zieglers 1992 study.

Cost is the main outcome reported.
Risk of bias
Bias
Authors judgement
Unclear risk
B - Unclear
Malhotra 1996
Methods

Participants
45 recruited.
BMT type: not specified
Age range: not specified
Interventions
Randomisation:
Elemental diet
Normal ad lib diet.
Start criteria - 72 hours pre high dose therapy.
Stop criteria: not stated.
Outcomes
Mucositis
Nausea
Diarrhoea
Sugar absorption tests for gastro-duodenal permeability, small bowel absorption and small
bowel permeability

20
Malhotra 1996
(Continued)
Notes
Abstract report only.
Risk of bias
Bias
Authors judgement
Unclear risk
B - Unclear
Mulder 1989
Methods

Participants
22 recruited.
BMT type: 22 Autologous
Disease type: 22 solid tumour
Age (range) years:
PN group = 28- 54 yrs
EN group = 21- 56 yrs.
Interventions
Randomisation:
11 PN
11 PN+EN
Start criteria:day + 4 after BMT
Stop criteria: leukocyte count > 1x 109.
Outcomes
Hospital duration
Survival
Notes
Risk of bias
Bias
Authors judgement
Unclear risk
B - Unclear
Muscaritoli 1998
Methods

Participants
66 recruited.
Age mean(range) years:

21
Muscaritoli 1998
(Continued)
Glucose based PN = 30.5 (15-47)

Lipid based PN = 29.1 (16-44)
Interventions
Randomisation:
35 PN Glucose
31 PN Lipid
Start criteria - day +1 after BMT.
Stop criteria - day + 16 after BMT.
Outcomes
Hospital duration
Change in body weight.
Survival
Notes
Follow up : 66 recruited, 6 withdrew.

35 PN Glucose (4 withdrew)
31 PN Lipid (2 withdrew)
Risk of bias
Bias
Authors judgement
Unclear risk
B - Unclear
Pytlik 2002
Methods
Randomised controlled trial method of randomisation is clear and apart from the hospital
pharmacists all other personnel were blind to the treatment allocation
Participants
40 recruited.
BMT type:
Autologous -40
Disease type: Haem malignancy -32
Solid tumour - 4
Other inherited conditions -4
Age range (mean +/-sd):
Intervention: (PN and Glutamine)
49 +/- 12
Control: Placebo
42+/-14
Interventions
Randomisation:
PN + glutamine - n=21
PN + placebo - n =19
Start criteria: administered from day +1 to day +14 or to discharge

22
Pytlik 2002
(Continued)
Outcomes
Mean days of Diarrhoea (>3 stools per day)

Mean oral energy intake
Mean days in hospital post transplantation
Mean days with severe mucositis
Days of PN
Notes
For most of the outcomes it did not appear that there was loss to follow up
Risk of bias
Bias
Authors judgement
Low risk
A - Adequate
Roberts 2003a
Methods

Method of randomisation is unclear as is the level of allocation concealment
Participants
55 recruited:
BMT type: Autologous -55
Disease type: Solid tumours (Breast cancer):55
Mean Age:
PN group:41.6 yrs
Oral diet group:45.6
Interventions
Randomisation:
PN:27
Oral diet:28
(also given IV fluids)
PN started day -1 were also allowed ad lib oral diet.
Outcomes
Nutritional status including:

% decrease in body weight
Nos with +ve blood cultures
No. days on antibiotics
Liver function
Change in mood disturbance
% probability of survival at 2 and 5 years.
Notes
Risk of bias
Bias
Authors judgement
Unclear risk
B - Unclear

23
Santos 2001
Methods
Randomised cross over controlled trial.

Method of randomisation is truly random although the extent of blinding of the participants
and the investigators is unclear
Participants
10 recruited:
BMT type: 10 allogeneic transplant patients
Disease type: all had haematological malignancies
Mean age: 36.7 years (sd 12.0).
Interventions
Randomisation:
Group 1: PN with lipid for 4 days and then PN without lipids for 4 days.
Intervention group 2: PN without lipids for 4 days and then PN with lipids for 4 days.
The composition of the PN lipid solution was given as 0.8 g/kg/d of 50:50 mixture of
medium and long chain triglycerides
Outcomes
Levels of cyclosporin in blood samples.
Notes
The authors reported that cyclosporin A pharmokinetics were not influenced by varying
types of lipid enriched PN admixtures
Risk of bias
Bias
Authors judgement
Unclear risk
B - Unclear
Scheltinga 1991
Methods

Participants
20 recruited.
Age( years)- mean(SEM)
PN + Glutamine - 36+/-3
Standard PN - 33+/-3
Interventions
Randomisation:
10 PN+Glutamine (0.57g/kg/day)
Outcomes
Hospital duration
Duration of PN

24
Scheltinga 1991
(Continued)
Notes

Small sub report from Zieglers 1992 study.
Risk of bias
Bias
Authors judgement
Unclear risk
B - Unclear
Schloerb 1993
Methods

Participants
29 recruited.
3 Solid tumour
Age (years) - mean (range)
PN + Glutamine 35.6(19-55)
Standard PN - 37.6 (19-55)
Interventions
Randomisation:
16 PN+ Glutamine (2830 mg glutamine/100 ml)
Start criteria - unclear
Stop criteria - oral intake >50% energy requirements.
Outcomes
Hospital duration
Mucositis
Duration of PN
Neutropaenia
Positive blood cultures
Notes
Risk of bias
Bias
Authors judgement
Low risk
A - Adequate

25
Schloerb 1999
Methods

Participants
66 recruited.
BMT type:19 Allogeneic/ 47 Autologous Disease type: 43 Haem malignancy
23 Solid tumour
Age: all > 17 yrs.
Interventions
Randomisation:
35 Oral Glutamine,10g x 3 /day.
33 Oral/PN Glycine, 10g x 3/day.
Start criteria: unclear.
Stop criteria: oral intake >50% energy requirement.
Outcomes
Hospital duration
Mucositis
Survival
Duration of PN
Notes
Risk of bias
Bias
Authors judgement
Low risk
A - Adequate
Szeluga 1987
Methods

Participants
65 recruited. 61 participated.
16 other miscellany of disorders.
Age (years)
PN = 21 > 19 yrs, 10 < 19 yrs.
EN group = 21 > 19 yrs, 9 < 19 yrs.
Interventions
Randomisation:
31PN
30 EN
(4 withdrew)
Start criteria: day before BMT
Stop criteria: 28 days after BMT

26
Szeluga 1987
(Continued)
Outcomes
Hospital duration
Duration of PN
Neutropaenia
Survival
Notes
65 recruited.
61 participated, 4 withdrew. 57 could be evaluated at day 28.
27 PN group (4 treatment failures).
30 EN group. (7 received PN).
Although 7 failed enteral feeds and received PN their outcomes were included in the EN
group analysis.
However 2 from the PN group were crossed at some stage into the EN group and were
included in the EN group analysis . Consequently numbers for each outcome presented
are unclear and none can be used
Risk of bias
Bias
Authors judgement
Unclear risk
B - Unclear
Takatsuka 2002
Methods

Participants
17 recruited.
BMT type: Allogeneic - 17
Disease type - haematological malignancy - 17
Age: < 17yrs - 1
>/= 17yrs - 16
Interventions
Randomisation:
8 - eicosapentaenoic acid(EPA) from day -21 to day 180 post BMT
9 - received nil
Outcomes
Numbers developing GVHD - graft versus host disease
Notes
Risk of bias
Bias
Authors judgement
Unclear risk
B - Unclear

27
Weisdorf 1987
Methods

Participants
137 recruited.
BMT type:104 Allogeneic/ 32 Autologous
Disease type:118 Haem malignancy
8 Solid tumour
3 Inherited disorder
5 Haem abnormalities
1 other malignancy
2 unaccounted
Age - years, mean (+/-SD) for
PN group = 20 (+/- 12.9)
IV hydration = 18.3 (+/- 12.9)
Interventions
Randomisation:
71 PN
66 IV Hydration.
Start criteria: 7 days before BMT.
Stop criteria: 4 weeks post BMT.
Outcomes
Hospital duration
Survival
Notes
Difficulty extracting data from paper.

There were no apparent losses to follow up.
Risk of bias
Bias
Authors judgement
Unclear risk
B - Unclear
Young 1993
Methods

Participants
23 recruited.
Age (yrs) (mean (range):
PN + Glutamine = 36 (20-49)
Standard PN = 30 (22-44)
Interventions
Randomisation:
13 PN + Glutamine (0.57g glutamine/kg/day)
10 Standard PN

28
Young 1993
(Continued)
Start criteria : Day + 1 after BMT.

Stop criteria : oral intake >50% energy requirements.
Outcomes
Hospital duration
Duration of PN
Notes

Small report from
Zieglers 1992 study.
Main outcome reported is mood.
Risk of bias
Bias
Authors judgement
Low risk
A - Adequate
Young 1997
Methods

Participants
20 recruited
BMT type:20 Allogeneic
Age: not specified
Allogeneic BMT patients.
Age - not specified
Interventions
Randomisation:
10 PN
10 EN
Start criteria: weight loss >10% nutritional requirements inadequate.
Stop criteria:not stated.
Outcomes
Duration of feeding (PN/EN

Notes

10 PN
10 EN ( 5 withdrew)
Abstract version only.
Risk of bias
Bias
Authors judgement

29
Young 1997
(Continued)
Unclear risk
B - Unclear
Ziegler 1992
Methods

Participants
45 recruited.
Age (years) - mean (range)
PN + Glutamine - 32.1(20-48)
Standard PN - 35.5(20-49)
Interventions
Randomisation:
24 PN+ Glutamine (0.57g/kg/day)
21 Standard PN ( no glutamine).
Outcomes
Hospital duration
Duration of PN
Mucositis
Neutropaenia
Positive blood cultures
Survival
Notes
Follow up: 45 recruited.

24 PN + Glutamine - 2 were not followed up for hospital duration but were for all other
outcomes reported.
21 Standard PN - (1 withdrew)
Note a number of studies are sub reports of this main study and they will not be included
in the analysis
Risk of bias
Bias
Authors judgement
Low risk
A - Adequate

30
Ziegler 1998
Methods

Participants
20 recruited.
Age (years) - mean (+/- SE)
PN + Glutamine - 36 (+/- 3
Standard PN - 35 (+/-3)
Interventions
Randomisation:
9 PN+ Glutamine (0.57 g/kg/day)
11 Standard PN ( no glutamine).
Start criteria - day+1 after BMT
Stop criteria - not stated
Outcomes
Duration of PN
Neutropaenia
Clinical infection
Notes

Small report from Zieglers main 1992 study.
Main outcome reported effect on circulating lymphocytes.
Risk of bias
Bias
Authors judgement
Unclear risk
B - Unclear
Characteristics of excluded studies [ordered by study ID]
Study
Reason for exclusion
Clemens 1997
This is not a randomised controlled trial.
Cohen 1996
This is not a report of a randomised controlled trial but single case report
Duggan 2004
These patients were not bone marrow transplant patients they were infants with gastrointestinal disease
Ford 1992
The study does not include bone marrow transplant patients.
Hopman 2003
This study compared enteral nutrition versus parenteral nutrition however the investigators combined data of
patients who were randomised into the study with patients who were not randomised into the study. Consequently the data from the randomised patients was merged with the data from the non randomised patients
preventing the data of the randomised patients to be evaluated

31
(Continued)
Klein 1994
This is not a report of a randomised controlled trial.
Lipman 1991a
This is not a report of a randomised controlled trial but a report of a review of clinical trials of nutrition support
in Cancer patients
Mercadante 1998a
This is not a report of a randomised controlled trial but a report on the benefits of enteral nutrition versus
parenteral nutrition for oncology patients
Mobrahan 1992
This is not a report of a randomised controlled trial but instead a report on the potential benefits of glutamine
for Bone Marrow Transplant patients
Piccirillo 2002
The data was presented in abstract form however it was not possible to adequately evaluate this study report
Piccirillo 2004
The data was presented in abstract form and was not evaluable
Poznarova 2003
Pytilik 2002a
Pytilik 2002b
Ramsay 1981
This randomised controlled trial did not use any form or type of nutrition support as its intervention
Reiffers 1996
This randomised controlled trial did not use any form or type of nutrition support as its intervention
Sax 1992
This is not a report of a randomised controlled trial but a comment report of a randomised controlled trial
(Ziegler 1992) that compared glutamine supplemented PN with standard PN
Schied 2004
This randomised controlled study which compared standard PN with PN and glutamine was conducted on
patients receiving intensive chemotherapy but they did not undergo bone marrow transplantation within this
study. This study is excluded because it did not meet the population inclusion criteria
Souba 1993
This is not a report of a randomised controlled trial but a comment report of other randomised controlled trials
that have compared glutamine supplemented PN with standard PN
Stern 2000
The intervention was related to early versus delayed discharge home and did not meet the inclusion criteria
Takatsuka 2001
This study is excluded since data from the same study published a year later is being included within this review
Ziegler 2001
This was not a randomised controlled trial but a review paper
Ziegler 2002
This was not a randomised controlled trial but a review paper

32
DATA AND ANALYSES
Comparison 1. Oral glutamine versus oral placebo studies
Outcome or subgroup title

1 Mean duration (+/-SD) of time
in hospital (e.g. admission to
discharge or from day 0 to
discharge).
2 Mean(+/-SD) number of days
patients had some degree of
mucositis from start to end of
study.
3 Number of patients who
developed line infections from
start to end of study.
4 Difference in mean % change in
body weight from start to end
of the study between the trial
groups.
5 Mean duration (+/-SD) that
nutritional intervention is
given as PN.
developed > grade 2 graft versus
host disease (GVHD).
7 Number of days(+/-SD) to
achieve normal neutrophil level
(>0.5 X 10/9/l) after day 0 of
BMT.
8 Actual numbers of patients who
have completed the study and
survived to the 100th day post
BMT.
9 Actual number of patients who
survived beyond day 100 post
BMT.
10 Number with positive blood
cultures
No. of
studies
No. of
participants
453
Mean Difference (IV, Fixed, 95% CI)
-2.39 [-6.11, 1.34]
335
0.0 [0.0, 0.0]
335
Peto Odds Ratio (Peto, Fixed, 95% CI)
0.0 [0.0, 0.0]
327
5.73 [-7.09, 18.55]
455
1.00 [-4.42, 2.43]
335
0.0 [0.0, 0.0]
335
6.82 [1.67, 11.98]
453
1.51 [0.88, 2.60]
453
0.0 [0.0, 0.0]
66
1.18 [0.39, 3.62]
Statistical method

Effect size
33
Comparison 2. PN + glutamine versus standard PN

1 Mean duration(+/-SD) of time
in hospital (e.g. admission to
discharge or from day 0 to
discharge home).
2 Mean(+/-SD) cumulative
mucositis score
groups.
given.
developed >/=grade 2 graft
versus host disease (GVHD).
BMT.
BMT.
9 Number of patients with positive
blood cultures
No. of
studies
No. of
participants
143
0.22 [-1.29, 1.72]
147
-0.02 [-0.48, 0.45]
110
0.0 [0.0, 0.0]
107
-0.34 [-1.40, 0.72]
147
0.36 [-1.63, 2.35]
109
0.57 [0.18, 1.83]
106
0.57 [-1.63, 2.76]
109
0.69 [0.16, 2.97]
147
0.46 [0.20, 1.04]
Statistical method
Effect size
Comparison 3. PN vs IV hydration

1 Mean duration (+/-SD) of time
in hospital (e.g. from discharge
admission to discharge or day 0
to discharge).
study.
No. of
studies
No. of
participants
221
3.30 [-0.38, 6.98]
221
0.0 [0.0, 0.0]
Statistical method

Effect size
34

groups.
given.
BMT.
BMT.
survived to day 200 post BMT.
10 Mean % change in albumin
217
21.23 [4.15, 108.73]
217
2.81 [1.34, 4.29]
221
12.2 [8.66, 15.74]
221
0.0 [0.0, 0.0]
221
0.0 [0.0, 0.0]
221
0.0 [0.0, 0.0]
221
2.10 [0.48, 9.18]
217
-3.72 [-5.96, -1.49]
Comparison 4. PN vs enteral feeding studies

1 Mean duration (+/-SD) of
time in hospital (e.g. from
admission to discharge or day 0
to discharge).
study.
groups.
given.
No. of
studies
No. of
participants
144
0.0 [0.0, 0.0]
144
0.0 [0.0, 0.0]
144
0.0 [0.0, 0.0]
144
0.0 [0.0, 0.0]
144
0.0 [0.0, 0.0]
Statistical method

Effect size
35

BMT.
BMT.
survived beyond day 200 post
BMT.
144
0.0 [0.0, 0.0]
144
0.0 [0.0, 0.0]
144
0.0 [0.0, 0.0]
144
0.0 [0.0, 0.0]
Comparison 5. Oral eicosapentaenoic acid supplementation versus nil

1 Numbers not developing graft
versus host disease
No. of
studies
No. of
participants
17
Statistical method
Odds Ratio (M-H, Fixed, 95% CI)

Effect size
12.09 [0.52, 280.40]
36
Analysis 1.1. Comparison 1 Oral glutamine versus oral placebo studies, Outcome 1 Mean duration (+/-SD)
of time in hospital (e.g. admission to discharge or from day 0 to discharge)..
Review:
Comparison: 1 Oral glutamine versus oral placebo studies

Outcome: 1 Mean duration (+/-SD) of time in hospital (e.g. admission to discharge or from day 0 to discharge).
Study or subgroup
Oral Glutamine
Mean
Difference
Placebo
Mean
Difference
Mean(SD)
Mean(SD)
Anderson 1998
98
0 (0)
95
0 (0)
0.0 [ 0.0, 0.0 ]
Aquino 2005
57
0 (0)
63
0 (0)
0.0 [ 0.0, 0.0 ]
29
0 (0)
29
0 (0)
0.0 [ 0.0, 0.0 ]
25.6 (2.2)
28.3 (5.5)
-2.70 [ -6.80, 1.40 ]
35
30.71 (15.19)
31
31.65 (20.69)
-0.94 [ -9.79, 7.91 ]
Jebb 1995
Schloerb 1999
Total (95% CI)
227
IV,Fixed,95% CI
IV,Fixed,95% CI
-2.39 [ -6.11, 1.34 ]
226
Heterogeneity: Chi2 = 0.12, df = 1 (P = 0.72); I2 =0.0%

Test for overall effect: Z = 1.26 (P = 0.21)
Test for subgroup differences: Not applicable
-10
-5
Oral Glutamine

10
Placebo
37
Analysis 1.2. Comparison 1 Oral glutamine versus oral placebo studies, Outcome 2 Mean(+/-SD) number of
days patients had some degree of mucositis from start to end of study..
Review:

Outcome: 2 Mean(+/-SD) number of days patients had some degree of mucositis from start to end of study.
Study or subgroup
Anderson 1998
Oral glutamine
N
Mean(SD)
Mean(SD)
0 (0)
95
0 (0)
0.0 [ 0.0, 0.0 ]
0 (0)
0 (0)
0.0 [ 0.0, 0.0 ]
29
0 (0)
29
0 (0)
0.0 [ 0.0, 0.0 ]
0 (0)
0 (0)
0.0 [ 0.0, 0.0 ]
35
0 (0)
31
0 (0)
0.0 [ 0.0, 0.0 ]
Jebb 1995
Schloerb 1999
Total (95% CI)
Mean
Difference
98
Aquino 2005
Mean
Difference
Placebo
171
IV,Fixed,95% CI
IV,Fixed,95% CI
0.0 [ 0.0, 0.0 ]
164
Heterogeneity: Chi2 = 0.0, df = 0 (P<0.00001); I2 =0.0%

Test for overall effect: Z = 0.0 (P < 0.00001)
-10
-5
Oral Glutamine

10
Placebo
38
Analysis 1.3. Comparison 1 Oral glutamine versus oral placebo studies, Outcome 3 Number of patients
who developed line infections from start to end of study..
Review:

Outcome: 3 Number of patients who developed line infections from start to end of study.
Study or subgroup
Peto
Odds Ratio
Peto
Odds Ratio
Oral Glutamine
Placebo
n/N
n/N
0/98
0/95
0.0 [ 0.0, 0.0 ]
0/1
0/1
0.0 [ 0.0, 0.0 ]
0/29
0/29
0.0 [ 0.0, 0.0 ]
0/8
0/8
0.0 [ 0.0, 0.0 ]
Schloerb 1999
0/35
0/31
0.0 [ 0.0, 0.0 ]
Total (95% CI)
171
164
0.0 [ 0.0, 0.0 ]
Anderson 1998
Aquino 2005
Jebb 1995
Peto,Fixed,95% CI
Peto,Fixed,95% CI
Total events: 0 (Oral Glutamine), 0 (Placebo)

0.1 0.2
0.5
Oral Glutamine

10
Placebo
39
Analysis 1.4. Comparison 1 Oral glutamine versus oral placebo studies, Outcome 4 Difference in mean %
change in body weight from start to end of the study between the trial groups..
Review:

Outcome: 4 Difference in mean % change in body weight from start to end of the study between the trial groups.
Study or subgroup
Oral Glutamine
Anderson 1998
Mean(SD)
Mean(SD)
0 (0)
95
0 (0)
0.0 [ 0.0, 0.0 ]
0 (0)
0 (0)
0.0 [ 0.0, 0.0 ]
29
0 (0)
29
0 (0)
0.0 [ 0.0, 0.0 ]
0 (0)
0 (0)
0.0 [ 0.0, 0.0 ]
32
0.06 (27.1)
26
-5.67 (22.7)
5.73 [ -7.09, 18.55 ]
Jebb 1995
Schloerb 1999
Total (95% CI)
Mean
Difference
98
Aquino 2005
Mean
Difference
Placebo
168
IV,Fixed,95% CI
IV,Fixed,95% CI
5.73 [ -7.09, 18.55 ]
159

-10
-5
Placebo

10
Oral Glutamine
40
Analysis 1.5. Comparison 1 Oral glutamine versus oral placebo studies, Outcome 5 Mean duration (+/-SD)
that nutritional intervention is given as PN..
Review:

Outcome: 5 Mean duration (+/-SD) that nutritional intervention is given as PN.
Study or subgroup
Oral Glutamine
Mean
Difference
Placebo
Mean
Difference
Mean(SD)
Mean(SD)
0 (0)
0 (0)
0.0 [ 0.0, 0.0 ]
Anderson 1998
98
0 (0)
95
0 (0)
0.0 [ 0.0, 0.0 ]
Aquino 2005
57
0 (0)
63
0 (0)
0.0 [ 0.0, 0.0 ]
29
0 (0)
29
0 (0)
0.0 [ 0.0, 0.0 ]
11.3 (5)
6.6 (4.2)
4.70 [ 0.18, 9.22 ]
35
8.89 (5.06)
31
17.55 (14.13)
-8.66 [ -13.91, -3.41 ]
Aldamiz 1996
Jebb 1995
Schloerb 1999
Total (95% CI)
228
IV,Fixed,95% CI
IV,Fixed,95% CI
227
-1.00 [ -4.42, 2.43 ]
Heterogeneity: Chi2 = 14.28, df = 1 (P = 0.00016); I2 =93%

-10
-5
Oral Glutamine

10
Placebo
41
Analysis 1.6. Comparison 1 Oral glutamine versus oral placebo studies, Outcome 6 Number of patients
who developed > grade 2 graft versus host disease (GVHD)..
Review:

Outcome: 6 Number of patients who developed > grade 2 graft versus host disease (GVHD).
Study or subgroup
Peto
Odds Ratio
Peto
Odds Ratio
Oral Glutamine
Placebo
n/N
n/N
0/98
0/95
0.0 [ 0.0, 0.0 ]
0/1
0/1
0.0 [ 0.0, 0.0 ]
0/29
0/29
0.0 [ 0.0, 0.0 ]
0/8
0/8
0.0 [ 0.0, 0.0 ]
Schloerb 1999
0/35
0/31
0.0 [ 0.0, 0.0 ]
Total (95% CI)
171
164
0.0 [ 0.0, 0.0 ]
Anderson 1998
Aquino 2005
Jebb 1995
Peto,Fixed,95% CI
Peto,Fixed,95% CI

0.1 0.2
0.5
Oral Glutamine

10
Placebo
42
Analysis 1.7. Comparison 1 Oral glutamine versus oral placebo studies, Outcome 7 Number of days(+/-SD)
to achieve normal neutrophil level (>0.5 X 10/9/l) after day 0 of BMT..
Review:

Outcome: 7 Number of days(+/-SD) to achieve normal neutrophil level (>0.5 X 10/9/l) after day 0 of BMT.
Study or subgroup
Anderson 1998
Oral Glutamine
N
Mean(SD)
Mean(SD)
0 (0)
95
0 (0)
0.0 [ 0.0, 0.0 ]
0 (0)
0 (0)
0.0 [ 0.0, 0.0 ]
29
0 (0)
29
0 (0)
0.0 [ 0.0, 0.0 ]
28.4 (11.5)
25.4 (11.7)
3.00 [ -8.37, 14.37 ]
35
19.26 (16.3)
31
11.45 (5.88)
7.81 [ 2.03, 13.59 ]
Jebb 1995
Schloerb 1999
Total (95% CI)
Mean
Difference
98
Aquino 2005
Mean
Difference
Placebo
171
IV,Fixed,95% CI
IV,Fixed,95% CI
6.82 [ 1.67, 11.98 ]
164

-10
-5
Oral Glutamine

10
Placebo
43
Analysis 1.8. Comparison 1 Oral glutamine versus oral placebo studies, Outcome 8 Actual numbers of
patients who have completed the study and survived to the 100th day post BMT..
Review:

Outcome: 8 Actual numbers of patients who have completed the study and survived to the 100th day post BMT.
Study or subgroup
Peto
Odds Ratio
Peto
Odds Ratio
Oral Glutamine
Placebo
n/N
n/N
Anderson 1998
86/98
77/95
1.66 [ 0.76, 3.61 ]
Aquino 2005
51/57
57/63
0.90 [ 0.27, 2.94 ]
0/29
0/29
0.0 [ 0.0, 0.0 ]
0/8
0/8
0.0 [ 0.0, 0.0 ]
Schloerb 1999
19/35
12/31
1.85 [ 0.71, 4.84 ]
Total (95% CI)
227
226
1.51 [ 0.88, 2.60 ]

Jebb 1995
Peto,Fixed,95% CI
Peto,Fixed,95% CI

0.1 0.2
0.5
Placebo

10
Oral Glutamine
44
Analysis 1.9. Comparison 1 Oral glutamine versus oral placebo studies, Outcome 9 Actual number of
patients who have completed the study and survived beyond day 100 post BMT..
Review:

Outcome: 9 Actual number of patients who have completed the study and survived beyond day 100 post BMT.
Study or subgroup
Peto
Odds Ratio
Peto
Odds Ratio
Oral Glutamine
Placebo
n/N
n/N
Anderson 1998
0/98
0/95
0.0 [ 0.0, 0.0 ]
Aquino 2005
0/57
0/63
0.0 [ 0.0, 0.0 ]
0/29
0/29
0.0 [ 0.0, 0.0 ]
0/8
0/8
0.0 [ 0.0, 0.0 ]
Schloerb 1999
0/35
0/31
0.0 [ 0.0, 0.0 ]
Total (95% CI)
227
226
0.0 [ 0.0, 0.0 ]
Jebb 1995
Peto,Fixed,95% CI
Peto,Fixed,95% CI

0.1 0.2
0.5
Oral Glutamine

10
Placebo
45
Analysis 1.10. Comparison 1 Oral glutamine versus oral placebo studies, Outcome 10 Number with
positive blood cultures.
Review:

Outcome: 10 Number with positive blood cultures
Study or subgroup
Peto
Odds Ratio
Peto
Odds Ratio
Treatment
Control
Weight
n/N
n/N
Schloerb 1999
9/35
7/31
100.0 %
1.18 [ 0.39, 3.62 ]
Total (95% CI)
35
31
100.0 %
1.18 [ 0.39, 3.62 ]
Peto,Fixed,95% CI
Peto,Fixed,95% CI
Total events: 9 (Treatment), 7 (Control)

Heterogeneity: not applicable
0.1 0.2
0.5
Favours treatment
10
Favours control
Analysis 2.1. Comparison 2 PN + glutamine versus standard PN, Outcome 1 Mean duration(+/-SD) of time
in hospital (e.g. admission to discharge or from day 0 to discharge home)..
Review:
Comparison: 2 PN + glutamine versus standard PN

Outcome: 1 Mean duration(+/-SD) of time in hospital (e.g. admission to discharge or from day 0 to discharge home).
Study or subgroup
PN + Glutamine
Mean
Difference
Standard PN
Weight
IV,Fixed,95% CI
Mean
Difference
Mean(SD)
Mean(SD)
IV,Fixed,95% CI
Brown 1998
16
28.25 (6.93)
16
37.44 (25.37)
1.4 %
-9.19 [ -22.08, 3.70 ]
Pytlik 2002
21
13.5 (3.1)
19
11.27 (2.4)
77.2 %
2.23 [ 0.52, 3.94 ]
Schloerb 1993
16
26.9 (5.2)
13
32.7 (7.57)
9.6 %
-5.80 [ -10.64, -0.96 ]
Ziegler 1992
22
29 (4.69)
20
36 (8.94)
11.8 %
-7.00 [ -11.38, -2.62 ]
Total (95% CI)
75
100.0 % 0.22 [ -1.29, 1.72 ]
68

-10
-5
PN + Glutamine

10
Standard PN
46
Analysis 2.2. Comparison 2 PN + glutamine versus standard PN, Outcome 2 Mean(+/-SD) cumulative
mucositis score.
Review:

Outcome: 2 Mean(+/-SD) cumulative mucositis score
Study or subgroup
PN + Glutamine
Mean
Difference
Standard PN
Mean
Difference
Mean(SD)
Mean(SD)
IV,Fixed,95% CI
IV,Fixed,95% CI
Brown 1998
18
0 (0)
16
0 (0)
0.0 [ 0.0, 0.0 ]
Pytlik 2002
21
13.5 (2.3)
19
12.6 (1.5)
0.90 [ -0.29, 2.09 ]
Schloerb 1993
16
0.7 (0.8)
13
0.9 (0.72)
-0.20 [ -0.75, 0.35 ]
Ziegler 1992
24
2.1 (1.96)
20
2.2 (2.23)
-0.10 [ -1.35, 1.15 ]
Total (95% CI)
79
-0.02 [ -0.48, 0.45 ]
68

-10
-5
PN + Glutamine

10
Standard PN
47
Analysis 2.3. Comparison 2 PN + glutamine versus standard PN, Outcome 3 Number of patients who
developed line infections from start to end of study..
Review:

Study or subgroup
Peto
Odds Ratio
Peto
Odds Ratio
PN + Glutamine
Standard PN
n/N
n/N
Brown 1998
0/18
0/16
0.0 [ 0.0, 0.0 ]
Pytlik 2002
0/1
0/1
0.0 [ 0.0, 0.0 ]
Schloerb 1993
0/16
0/13
0.0 [ 0.0, 0.0 ]
Ziegler 1992
0/24
0/21
0.0 [ 0.0, 0.0 ]
Total (95% CI)
59
51
0.0 [ 0.0, 0.0 ]
Peto,Fixed,95% CI
Peto,Fixed,95% CI
Total events: 0 (PN + Glutamine), 0 (Standard PN)

0.1 0.2
0.5
PN + Glutamine

10
Standard PN
48
Analysis 2.4. Comparison 2 PN + glutamine versus standard PN, Outcome 4 Difference in mean % change
in body weight from start to end of the study between the trial groups..
Review:

Study or subgroup
PN + Glutamine
Mean
Difference
Standard PN
Mean
Difference
Mean(SD)
Mean(SD)
Brown 1998
16
-6.85 (1.74)
15
-7.45 (2.54)
IV,Fixed,95% CI
0.60 [ -0.94, 2.14 ]
IV,Fixed,95% CI
Pytlik 2002
0 (0)
0 (0)
0.0 [ 0.0, 0.0 ]
Schloerb 1993
16
-0.61 (1.17)
13
0.56 (2.46)
-1.17 [ -2.62, 0.28 ]
Ziegler 1992
24
0 (0)
21
0 (0)
0.0 [ 0.0, 0.0 ]
Total (95% CI)
57
50
-0.34 [ -1.40, 0.72 ]

-10
-5
Standard PN

10
PN + Glut
49
Analysis 2.5. Comparison 2 PN + glutamine versus standard PN, Outcome 5 Mean duration (+/-SD) that
nutritional intervention is given..
Review:

Outcome: 5 Mean duration (+/-SD) that nutritional intervention is given.
Study or subgroup
PN + Glutamine
Mean
Difference
Standard PN
Weight
Mean
Difference
Mean(SD)
Mean(SD)
Brown 1998
18
23.22 (10.22)
16
18.81 (11.72)
IV,Fixed,95% CI
7.1 %
4.41 [ -3.02, 11.84 ]
IV,Fixed,95% CI
Pytlik 2002
21
3.5 (4.2)
19
2.8 (3.5)
69.3 %
0.70 [ -1.69, 3.09 ]
Schloerb 1993
16
30 (20)
13
31 (10.82)
3.0 %
-1.00 [ -12.43, 10.43 ]
Ziegler 1992
24
26 (9.8)
20
28 (4.47)
20.6 %
-2.00 [ -6.38, 2.38 ]
Total (95% CI)
79
68
100.0 % 0.36 [ -1.63, 2.35 ]

-10
-5
PN + Glutamine

10
Standard PN
50
Analysis 2.6. Comparison 2 PN + glutamine versus standard PN, Outcome 6 Number of patients who
developed >/=grade 2 graft versus host disease (GVHD)..
Review:

Outcome: 6 Number of patients who developed >/=grade 2 graft versus host disease (GVHD).
Study or subgroup
Peto
Odds Ratio
Peto
Odds Ratio
PN + Glutamine
Standard PN
n/N
n/N
Brown 1998
0/18
3/16
0.10 [ 0.01, 1.08 ]
Pytlik 2002
0/1
0/1
0.0 [ 0.0, 0.0 ]
Schloerb 1993
0/16
0/13
0.0 [ 0.0, 0.0 ]
Ziegler 1992
6/24
5/20
1.00 [ 0.26, 3.88 ]
Total (95% CI)
59
50
0.57 [ 0.18, 1.83 ]
Peto,Fixed,95% CI
Peto,Fixed,95% CI

0.1 0.2
0.5
PN + Glutamine

10
Standard PN
51
Analysis 2.7. Comparison 2 PN + glutamine versus standard PN, Outcome 7 Number of days(+/-SD) to
achieve normal neutrophil level (>0.5 X 10/9/l) after day 0 of BMT..
Review:

Study or subgroup
PN + Glutamine
Mean
Difference
Standard PN
Mean
Difference
Mean(SD)
Mean(SD)
Brown 1998
17
14.88 (5.33)
14
17.36 (7.74)
IV,Fixed,95% CI
-2.48 [ -7.26, 2.30 ]
IV,Fixed,95% CI
Pytlik 2002
0 (0)
0 (0)
0.0 [ 0.0, 0.0 ]
Schloerb 1993
16
14 (8)
13
15 (6.85)
-1.00 [ -6.41, 4.41 ]
Ziegler 1992
24
20 (4.9)
20
18 (4.47)
2.00 [ -0.77, 4.77 ]
Total (95% CI)
58
48
0.57 [ -1.63, 2.76 ]

-10
-5
PN + Glutamine

10
Standard PN
52
Analysis 2.8. Comparison 2 PN + glutamine versus standard PN, Outcome 8 Actual numbers of patients
who have completed the study and survived to the 100th day post BMT..
Review:

Study or subgroup
Peto
Odds Ratio
Peto
Odds Ratio
PN + Glutamine
Standard PN
n/N
n/N
17/18
15/16
1.13 [ 0.07, 18.94 ]
0/1
0/1
0.0 [ 0.0, 0.0 ]
0/16
0/13
0.0 [ 0.0, 0.0 ]
20/24
18/20
0.58 [ 0.10, 3.18 ]
59
50
0.69 [ 0.16, 2.97 ]
Brown 1998
Pytlik 2002
Schloerb 1993
Ziegler 1992
Total (95% CI)
Peto,Fixed,95% CI
Peto,Fixed,95% CI

0.1 0.2
0.5
PN + Glutamine

10
Standard PN
53
Analysis 2.9. Comparison 2 PN + glutamine versus standard PN, Outcome 9 Number of patients with
positive blood cultures.
Review:

Outcome: 9 Number of patients with positive blood cultures
Study or subgroup
Peto
Odds Ratio
Peto
Odds Ratio
PN + Glutamine
Standard PN
n/N
n/N
Brown 1998
0/18
0/16
0.0 [ 0.0, 0.0 ]
Pytlik 2002
8/21
6/19
1.32 [ 0.37, 4.78 ]
Schloerb 1993
11/16
11/13
0.43 [ 0.08, 2.33 ]
Ziegler 1992
14/24
19/20
0.15 [ 0.04, 0.57 ]
79
68
0.46 [ 0.20, 1.04 ]
Total (95% CI)
Peto,Fixed,95% CI
Peto,Fixed,95% CI

0.1 0.2
0.5
Favours PN+Glutamine

10
Favours Standard PN
54
Analysis 3.1. Comparison 3 PN vs IV hydration, Outcome 1 Mean duration (+/-SD) of time in hospital (e.g.
from discharge admission to discharge or day 0 to discharge)..
Review:
Comparison: 3 PN vs IV hydration
Outcome: 1 Mean duration (+/-SD) of time in hospital (e.g. from discharge admission to discharge or day 0 to discharge).
Study or subgroup
Parenteral nutrition
Mean
Difference
Intravenous hydratn
Mean
Difference
Mean(SD)
Mean(SD)
Lough 1990
14
0 (0)
15
0 (0)
0.0 [ 0.0, 0.0 ]
Roberts 2003a
27
28.7 (8.8)
28
25.4 (4.3)
3.30 [ -0.38, 6.98 ]
Weisdorf 1987
71
0 (0)
66
0 (0)
0.0 [ 0.0, 0.0 ]
Total (95% CI)
112
IV,Fixed,95% CI
IV,Fixed,95% CI
109
3.30 [ -0.38, 6.98 ]

-10
-5
Favours PN

10
Favours IV
55
Analysis 3.2. Comparison 3 PN vs IV hydration, Outcome 2 Mean(+/-SD) number of days patients had some
degree of mucositis from start to end of study..
Review:
Study or subgroup
Mean
Difference
Intravenous Hydratn
Mean
Difference
Mean(SD)
Mean(SD)
Lough 1990
14
0 (0)
15
0 (0)
0.0 [ 0.0, 0.0 ]
Roberts 2003a
27
0 (0)
28
0 (0)
0.0 [ 0.0, 0.0 ]
Weisdorf 1987
71
0 (0)
66
0 (0)
0.0 [ 0.0, 0.0 ]
Total (95% CI)
112
IV,Fixed,95% CI
IV,Fixed,95% CI
109
0.0 [ 0.0, 0.0 ]

-10
-5
Favours PN

10
Favours IV
56
Analysis 3.3. Comparison 3 PN vs IV hydration, Outcome 3 Number of patients who developed line
infections from start to end of study..
Review:
Study or subgroup
Peto
Odds Ratio
Peto
Odds Ratio
Intravenous hydratn
n/N
n/N
Lough 1990
8/10
1/15
21.23 [ 4.15, 108.73 ]
Roberts 2003a
0/27
0/28
0.0 [ 0.0, 0.0 ]
Weisdorf 1987
0/71
0/66
0.0 [ 0.0, 0.0 ]
Total (95% CI)
108
109
21.23 [ 4.15, 108.73 ]
Peto,Fixed,95% CI
Peto,Fixed,95% CI
Total events: 8 (Parenteral nutrition), 1 (Intravenous hydratn)

0.1 0.2
0.5
Favours PN

10
Favours IV
57
Analysis 3.4. Comparison 3 PN vs IV hydration, Outcome 4 Difference in mean % change in body weight
from start to end of the study between the trial groups..
Review:
Study or subgroup
Mean
Difference
Intravenous hydratn
Mean
Difference
Mean(SD)
Mean(SD)
Lough 1990
10
-4.42 (2.3)
15
-7.18 (0.9)
2.76 [ 1.26, 4.26 ]
Roberts 2003a
27
-2 (13.8)
28
-6.5 (17.7)
4.50 [ -3.87, 12.87 ]
Weisdorf 1987
71
0 (0)
66
0 (0)
0.0 [ 0.0, 0.0 ]
Total (95% CI)
108
IV,Fixed,95% CI
IV,Fixed,95% CI
109
2.81 [ 1.34, 4.29 ]

-10
-5
Favours IV

10
Favours PN
58
Analysis 3.5. Comparison 3 PN vs IV hydration, Outcome 5 Mean duration (+/-SD) that nutritional
intervention is given..
Review:
Study or subgroup
Mean
Difference
Intravenous Hydratn
Mean
Difference
Mean(SD)
Mean(SD)
Lough 1990
14
10 (4)
15
0 (0)
0.0 [ 0.0, 0.0 ]
Roberts 2003a
27
17.5 (7.4)
28
5.3 (5.9)
12.20 [ 8.66, 15.74 ]
Weisdorf 1987
71
0 (0)
66
0 (0)
0.0 [ 0.0, 0.0 ]
Total (95% CI)
112
IV,Fixed,95% CI
IV,Fixed,95% CI
109
12.20 [ 8.66, 15.74 ]

-10
-5
Favours PN

10
Favours IV
59
Analysis 3.6. Comparison 3 PN vs IV hydration, Outcome 6 Number of patients who developed > grade 2
graft versus host disease (GVHD)..
Review:
Study or subgroup
Peto
Odds Ratio
Peto
Odds Ratio
Intravenous Hydratn
n/N
n/N
Lough 1990
0/14
0/15
0.0 [ 0.0, 0.0 ]
Roberts 2003a
0/27
0/28
0.0 [ 0.0, 0.0 ]
Weisdorf 1987
0/71
0/66
0.0 [ 0.0, 0.0 ]
Total (95% CI)
112
109
0.0 [ 0.0, 0.0 ]
Peto,Fixed,95% CI
Peto,Fixed,95% CI
Total events: 0 (Parenteral nutrition), 0 (Intravenous Hydratn)

0.1 0.2
0.5
Favours PN

10
Favours IV
60
Analysis 3.7. Comparison 3 PN vs IV hydration, Outcome 7 Number of days(+/-SD) to achieve normal

neutrophil level (>0.5 X 10/9/l) after day 0 of BMT..
Review:
Study or subgroup
Mean
Difference
Intravenous hydratn
Mean
Difference
Mean(SD)
Mean(SD)
Lough 1990
14
0 (0)
15
0 (0)
0.0 [ 0.0, 0.0 ]
Roberts 2003a
27
0 (0)
28
0 (0)
0.0 [ 0.0, 0.0 ]
Weisdorf 1987
71
0 (0)
66
0 (0)
0.0 [ 0.0, 0.0 ]
Total (95% CI)
112
IV,Fixed,95% CI
IV,Fixed,95% CI
109
0.0 [ 0.0, 0.0 ]

-10
-5
Favours PN

10
Favours IV
61
Analysis 3.8. Comparison 3 PN vs IV hydration, Outcome 8 Actual numbers of patients who have
completed the study and survived to the 100th day post BMT..
Review:
Study or subgroup
Peto
Odds Ratio
Peto
Odds Ratio
Intravenous hydratn
n/N
n/N
Lough 1990
0/14
0/15
0.0 [ 0.0, 0.0 ]
Roberts 2003a
0/27
0/28
0.0 [ 0.0, 0.0 ]
Weisdorf 1987
0/71
0/66
0.0 [ 0.0, 0.0 ]
Total (95% CI)
112
109
0.0 [ 0.0, 0.0 ]
Peto,Fixed,95% CI
Peto,Fixed,95% CI

0.1 0.2
0.5
Favours PN

10
Favours IV
62
Analysis 3.9. Comparison 3 PN vs IV hydration, Outcome 9 Actual number of patients who survived to day
200 post BMT..
Review:
Outcome: 9 Actual number of patients who survived to day 200 post BMT.
Study or subgroup
Peto
Odds Ratio
Peto
Odds Ratio
Intravenous hydratn
n/N
n/N
10/14
8/15
2.10 [ 0.48, 9.18 ]
Roberts 2003a
0/27
0/28
0.0 [ 0.0, 0.0 ]
Weisdorf 1987
0/71
0/66
0.0 [ 0.0, 0.0 ]
Total (95% CI)
112
109
2.10 [ 0.48, 9.18 ]
Lough 1990
Peto,Fixed,95% CI
Peto,Fixed,95% CI

0.1 0.2
0.5
Favours IV

10
Favours PN
63
Analysis 3.10. Comparison 3 PN vs IV hydration, Outcome 10 Mean % change in albumin.

Review:
Outcome: 10 Mean % change in albumin
Study or subgroup
PN
Mean
Difference
Intravenous hydratio
Mean
Difference
Mean(SD)
Mean(SD)
Lough 1990
10
-1.24 (5.3)
15
4.69 (4.4)
-5.93 [ -9.90, -1.96 ]
Roberts 2003a
27
12.9 (6)
28
15.6 (4)
-2.70 [ -5.41, 0.01 ]
Weisdorf 1987
71
0 (0)
66
0 (0)
0.0 [ 0.0, 0.0 ]
Total (95% CI)
108
IV,Fixed,95% CI
IV,Fixed,95% CI
109
-3.72 [ -5.96, -1.49 ]

-10
-5
Favours IV

10
Favours PN
64
Analysis 4.1. Comparison 4 PN vs enteral feeding studies, Outcome 1 Mean duration (+/-SD) of time in
hospital (e.g. from admission to discharge or day 0 to discharge)..
Review:
Comparison: 4 PN vs enteral feeding studies

Outcome: 1 Mean duration (+/-SD) of time in hospital (e.g. from admission to discharge or day 0 to discharge).
Study or subgroup
Enteral
Mean
Difference
Parenteral
Mean
Difference
Mean(SD)
Mean(SD)
Cope 1997
23
0 (0)
40
0 (0)
0.0 [ 0.0, 0.0 ]
Szeluga 1987
30
0 (0)
31
0 (0)
0.0 [ 0.0, 0.0 ]
Young 1997
10
0 (0)
10
0 (0)
0.0 [ 0.0, 0.0 ]
Total (95% CI)
63
IV,Fixed,95% CI
IV,Fixed,95% CI
81
0.0 [ 0.0, 0.0 ]

-10
-5
Favours Enteral

10
Favours Parenteral
65
Analysis 4.2. Comparison 4 PN vs enteral feeding studies, Outcome 2 Mean(+/-SD) number of days patients
had some degree of mucositis from start to end of study..
Review:

Study or subgroup
Enteral
Mean
Difference
Parenteral
Mean
Difference
Mean(SD)
Mean(SD)
Cope 1997
23
0 (0)
40
0 (0)
0.0 [ 0.0, 0.0 ]
Szeluga 1987
30
0 (0)
31
0 (0)
0.0 [ 0.0, 0.0 ]
Young 1997
10
0 (0)
10
0 (0)
0.0 [ 0.0, 0.0 ]
Total (95% CI)
63
IV,Fixed,95% CI
IV,Fixed,95% CI
81
0.0 [ 0.0, 0.0 ]

-10
-5
Favours enteral

10
Favours parenteral
66
Analysis 4.3. Comparison 4 PN vs enteral feeding studies, Outcome 3 Number of patients who developed
line infections from start to end of study..
Review:

Study or subgroup
Peto
Odds Ratio
Peto
Odds Ratio
Enteral
Parenteral
n/N
n/N
Cope 1997
0/23
0/40
0.0 [ 0.0, 0.0 ]
Szeluga 1987
0/30
0/31
0.0 [ 0.0, 0.0 ]
Young 1997
0/10
0/10
0.0 [ 0.0, 0.0 ]
63
81
0.0 [ 0.0, 0.0 ]
Total (95% CI)
Peto,Fixed,95% CI
Peto,Fixed,95% CI
Total events: 0 (Enteral), 0 (Parenteral)

0.1 0.2
0.5
Favours Enteral

10
Favours Parenteral
67
Analysis 4.4. Comparison 4 PN vs enteral feeding studies, Outcome 4 Difference in mean % change in body
weight from start to end of the study between the trial groups..
Review:

Study or subgroup
Enteral
Mean
Difference
Parenteral
Mean
Difference
Mean(SD)
Mean(SD)
Cope 1997
23
0 (0)
40
0 (0)
0.0 [ 0.0, 0.0 ]
Szeluga 1987
30
0 (0)
31
0 (0)
0.0 [ 0.0, 0.0 ]
Young 1997
10
0 (0)
10
0 (0)
0.0 [ 0.0, 0.0 ]
Total (95% CI)
63
IV,Fixed,95% CI
IV,Fixed,95% CI
81
0.0 [ 0.0, 0.0 ]

-10
-5
Favours Parenteral

10
Favours enteral
68
Analysis 4.5. Comparison 4 PN vs enteral feeding studies, Outcome 5 Mean duration (+/-SD) that
nutritional intervention is given..
Review:

Study or subgroup
Enteral
Mean
Difference
Parenteral
Mean
Difference
Mean(SD)
Mean(SD)
Cope 1997
23
0 (0)
40
0 (0)
0.0 [ 0.0, 0.0 ]
Szeluga 1987
30
0 (0)
31
0 (0)
0.0 [ 0.0, 0.0 ]
Young 1997
10
0 (0)
10
0 (0)
0.0 [ 0.0, 0.0 ]
Total (95% CI)
63
IV,Fixed,95% CI
IV,Fixed,95% CI
81
0.0 [ 0.0, 0.0 ]

-10
-5
Favours enteral

10
Favours parenteral
69
Analysis 4.6. Comparison 4 PN vs enteral feeding studies, Outcome 6 Number of patients who developed >
grade 2 graft versus host disease (GVHD)..
Review:

Study or subgroup
Peto
Odds Ratio
Peto
Odds Ratio
Enteral
Parenteral
n/N
n/N
Cope 1997
0/23
0/40
0.0 [ 0.0, 0.0 ]
Szeluga 1987
0/30
0/31
0.0 [ 0.0, 0.0 ]
Young 1997
0/10
0/10
0.0 [ 0.0, 0.0 ]
63
81
0.0 [ 0.0, 0.0 ]
Total (95% CI)
Peto,Fixed,95% CI
Peto,Fixed,95% CI

0.1 0.2
0.5
Favours enteral

10
Favours parenteral
70
Analysis 4.7. Comparison 4 PN vs enteral feeding studies, Outcome 7 Number of days(+/-SD) to achieve
normal neutrophil level (>0.5 X 10/9/l) after day 0 of BMT..
Review:

Study or subgroup
Enteral
Mean
Difference
Parenteral
Mean
Difference
Mean(SD)
Mean(SD)
Cope 1997
23
0 (0)
40
0 (0)
0.0 [ 0.0, 0.0 ]
Szeluga 1987
30
0 (0)
31
0 (0)
0.0 [ 0.0, 0.0 ]
Young 1997
10
0 (0)
10
0 (0)
0.0 [ 0.0, 0.0 ]
Total (95% CI)
63
IV,Fixed,95% CI
IV,Fixed,95% CI
81
0.0 [ 0.0, 0.0 ]

-10
-5
Favours enteral

10
Favours parenteral
71
Analysis 4.8. Comparison 4 PN vs enteral feeding studies, Outcome 8 Actual numbers of patients who have
completed the study and survived to the 100th day post BMT..
Review:

Study or subgroup
Peto
Odds Ratio
Peto
Odds Ratio
Enteral
Parenteral
n/N
n/N
Cope 1997
0/23
0/40
0.0 [ 0.0, 0.0 ]
Szeluga 1987
0/30
0/31
0.0 [ 0.0, 0.0 ]
Young 1997
0/10
0/10
0.0 [ 0.0, 0.0 ]
63
81
0.0 [ 0.0, 0.0 ]
Total (95% CI)
Peto,Fixed,95% CI
Peto,Fixed,95% CI

0.1 0.2
0.5
Favours enteral

10
Favours parenteral
72
Analysis 4.9. Comparison 4 PN vs enteral feeding studies, Outcome 9 Actual number of patients who have
completed the study and survived beyond day 200 post BMT..
Review:

Outcome: 9 Actual number of patients who have completed the study and survived beyond day 200 post BMT.
Study or subgroup
Peto
Odds Ratio
Peto
Odds Ratio
Enteral
Parenteral
n/N
n/N
Cope 1997
0/23
0/40
0.0 [ 0.0, 0.0 ]
Szeluga 1987
0/30
0/31
0.0 [ 0.0, 0.0 ]
Young 1997
0/10
0/10
0.0 [ 0.0, 0.0 ]
63
81
0.0 [ 0.0, 0.0 ]
Total (95% CI)
Peto,Fixed,95% CI
Peto,Fixed,95% CI

0.1 0.2
0.5
Favours enteral
10
Favours parenteral
Analysis 5.1. Comparison 5 Oral eicosapentaenoic acid supplementation versus nil, Outcome 1 Numbers
not developing graft versus host disease.
Review:
Comparison: 5 Oral eicosapentaenoic acid supplementation versus nil

Outcome: 1 Numbers not developing graft versus host disease
Study or subgroup
Takatsuka 2002
Treatment
Control
Odds Ratio
n/N
n/N
M-H,Fixed,95% CI
3/8
0/9
100.0 %
12.09 [ 0.52, 280.40 ]
100.0 %
12.09 [ 0.52, 280.40 ]
Total (95% CI)
Weight
Odds Ratio
M-H,Fixed,95% CI
Total events: 3 (Treatment), 0 (Control)

Heterogeneity: not applicable
0.1 0.2
0.5
Favours treatment
10
Favours control

73
ADDITIONAL TABLES
Table 1. Summary table - Quality of studies assessed
Study ID
Randomisation
Allocation con- Double blind

ceal
Participants
masked
Clinicians
masked
Assessors
masked
Anderson 1998
Truly random
Adequate
Yes
Yes
Yes
Yes
Jebb 1995
Unclear
Unclear
Yes
Yes
Yes
Yes
Schloerb 1999
Truly random
Adequate
Yes
Yes
Yes
Yes
Coghlin
Dickson 2000
Unclear
Unclear
Yes
Yes
Unclear
Unclear
Brown 1998
Truly random
Adequate
Yes
Yes
Yes
Yes
Schloerb 1993
Truly random
Adequate
Yes
Yes
Yes
Yes
Ziegler 1992
Unclear
Adequate
Yes
Yes
Yes
Uncertain
Lough 1990
Truly random
Adequate
No
No
No
No
Weisdorf 1987
Unclear
Unclear
No
Uncertain
Uncertain
Uncertain
Szeluga 1987
Unclear
Unclear
No
Uncertain
Uncertain
Uncertain
Young 1997
Unclear
Unclear
No
Uncertain
Uncertain
Uncertain
Cope 1997
Unclear
Unclear
No
Uncertain
Uncertain
Uncertain
Macburney
1994
Unclear
Unclear
Yes
Yes
Yes
Yes
Scheltinga 1991
Unclear
Unclear
Yes
Yes
Yes
Uncertain
Young 1993
Unclear
Unclear
Yes
Yes
Yes
Yes
Ziegler 1998
Unclear
Unclear
Yes
Uncertain
Uncertain
Uncertain
Charhuas 1997
Unclear
Unclear
Yes
Yes
Yes
Yes
Mulder 1989
Unclear
Unclear
No
Uncertain
Uncertain
Uncertain
Lenssen 1998
Unclear
Unclear
Uncertain
Uncertain
Uncertain
Uncertain

74
Table 1. Summary table - Quality of studies assessed
(Continued)
Aldamiz 1996
Unclear
Unclear
Uncertain
Uncertain
Uncertain
Uncertain
Lenssen 1987
Truly random
Adequate
Yes
Yes
Yes
Yes
Malhotra 1996
Unclear
Unclear
Uncertain
Uncertain
Uncertain
Uncertain
Muscaritoli
1998
Unclear
Unclear
No
No
No
Uncertain
Takatsuka 2002
Unclear
Unclear
No
Uncertain
Uncertain
Uncertain
Roberts 2003a
Unclear
Unclear
No
No
No
Uncertain
Pytilik 2002
Truly random
Adequate
Yes
Yes
Yes
Yes
Santos 2001
Truly random
Adequate
Uncertain
Uncertain
Uncertain
Uncertain
Aquino 2005
Truly random
Adequate
Yes
Unclear
Unclear
Unclear
Jimenez 1999
APPENDICES
Appendix 1. Example search strategy
#1 explode Nutrition/ all subheadings
#2 explode Nutrition-Assessment/ all subheadings
#3 explode Feeding-Methods/ all subheadings
#4 Intubation,-Gastrointestinal/ all subheadings
#5 Gastrostomy/ all subheadings
#6 Eating/ all subheadings
#7 explode Foods,-Specialized/ all subheadings
#8 explode Food/ all subheadings
#9 explode Feeding-Behavior/ all subheadings
#10 explode Appetite/ all subheadings
#11 Jejunostomy/ all subheadings
#12 Glutamine/ all subheadings
#13 glutamin*
#14 nutrition*
#15 food*
#16 feed*
#17 nasogastr*
#18 nasojejun*
#19 nasoduoden*
#20 gastrostom*
75
#21 gastrojejunostom*
#22 naso near duoden*
#23 naso near1 gastr*
#24 jejun*
#25 bolus*
#26 intub*
#27 appetite*
#28 parenteral*
#29 calor*
#30 intake*
#31 sip*
#32 oral*
#33 diet*
#34 intraven*
#35 enteral*
#36 tube*
#37 supplement*
#38 fortif*
#39 formula*
#40 eat*
#41 hydrolysate*
#42 novel* substrate*
#43 elemental
#44 PN in TI,TO,CM,AB
#45 EN in TI,TO,CM,AB
#46 TPN in TI,TO,CM,AB
#47 NG in TI,TO,CM,AB
#48 PEG in TI,TO,CM,AB
#49 Bone-Marrow-Transplantation/ all subheadings
#50 bone marrow near transplan*
#51 Peripheral blast stem cell transplan*
#52 BMT*
#53 MATCH* SIB* DON*
#54 MATCH* UNREL* DON*
#56 PBSCT*
#57 #1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9 or #10 or #11 or #12 or #13 # or #14 or #15 or #16 or #17 or #18 or #19 or #
20 or #21 or #22 or #23 or #24 or #5 or #26 or #27 or #28 or #29 or #30 or #31 or #32 or #33 or #34 or #35 or #36 or #37 or #38
or #39 or #40 or #41 or #42 or #43 or #44 or #45 or #46 or #47 or #48
#58 #49 or #50 or #51 or #52 or #53 or #54 or #55 or #56
#59 #57 and #58
FEEDBACK

76
Including the study by Pytlik 2002, 2 October 2013
Summary
With regard to the analysis Parenteral nutrition with glutamine versus standard parenteral nutrition I would respectfully ask the authors
to consider the appropriateness of including the study by Pytlik 2002. The intervention group received daily GLN supplementation
from day +1 to day +14 of transplant regardless of their need for PN. In fact the intervention group received PN for just 3.5 days on
average. Hence this study was not of glutamine supplemented PN.If there is a benefit of GLN it is likely to be in those patients requiring
nutritional support as per the other studies originally included (Ziegler and Schloerb). Subsequent studies have shown a benefit in
allogeneic but not autologous transplant patients - if this review were to be updated it would be very useful to see meta-analysis per
transplant type
Name: Julie Beckerson
Affiliation: Imperial College Healthcare NHS Trust
Role: Haematology Dietitian
Reply
The inclusion criteria for this review were: Study type- Randomised Controlled Trial, Patient type - receiving any type of bone marrow
transplant, and the Type of Intervention- must compare one form of enteral or parenteral nutrition with another mode of nutrition
support or IV fluid. There was no minimum or maximum duration specified for receiving the intervention.
With the Pytilik 2002 study, the intervention group received daily GLN supplementation from day +1 to day +14 of transplant
regardless of their need for PN. The intervention group received PN for just 3.5 days on average.
The duration for receiving the PN with or without GLN (albeit for an average of 3.5 days ) was not a reason for excluding this study.
The hypothesis being that we do not know the optimum duration for receiving the intervention. This remains an included study.
In a future update a meta-analysis for the different types of transplants would be worthy to investigate.
Contributors
Susan Murray, Royal College of Physicians.
WHATS NEW
Last assessed as up-to-date: 30 April 2008.
Date
Event
Description
4 April 2014
Amended
This review has been withdrawn. Please see Published notes.

77
HISTORY
Protocol first published: Issue 1, 2001
Review first published: Issue 2, 2002
Date
Event
Description
4 April 2014
Feedback has been incorporated
Feedback added regarding a query about the appropriateness of the Pytilik 2002 study for inclusion. See
Feedback.
12 November 2008
Amended
Contact details updated
13 August 2008
Amended
This review update should have been put up for publication in Issue 3, 2008 but unfortunately due to technical error did not make it
14 May 2008
Amended
Converted to new review format.
30 April 2008
New citation required and conclusions have changed
This review is made up of four small sub reviews. For

the update of this review 17 potential studies were
identified in the re-run of the search which was conducted in June 2006. Five of the 17 studies were included, three of which were grouped within three other
reviews which are included in this review that is:
Oral Glutamine versus placebo (one study Aquino
2005 (n = 120 children)), Parenteral nutrition (PN)
with Glutamine versus standard PN (one study Pytilik
2002 (n = 40)) and Parenteral nutrition versus Intravenous hydration (one study Roberts 2003 (n = 55))
. The two other studies were not pooled but added to
the eight other heterogenous studies identified in the
original review
The addition of data from the studies by Aquino 2005
and Roberts 2003 does not affect the results or conclusions of the sub reviews that they were part of. However, for the sub review that compared PN with additional glutamine versus standard PN, following further
analysis with the additional data from Pytilik 2002 the
pooled result for hospital duration did not show the
same benefit to patients who received the intervention PN with Glutamine in that, hospital duration no
longer seemed to be reduced for patients who received
the intervention. However, the likelihood that these
patients will have less infections remains the same. In
the original review of this material we proposed that
for patients who were unable to have an adequate oral
diet and who had gastrointestinal failure resulting in
the need for PN, PN with added glutamine should be

78
(Continued)
considered. We would now alter this to say that giving patients PN with additional glutamine could be of
benefit but also further research on this is required to
further confirm this.
Previous readers of this review would benefit from
reading this updated review
CONTRIBUTIONS OF AUTHORS
SM & SP both worked on the protocol, review and the update with SM primarily writing up the revisions to the text for the update.
DECLARATIONS OF INTEREST
None known
NOTES
This review is now out of date although it is correct as of the date of publication [Issue 4, 2008]. The original author team is unable
to complete the update, hence the decision to withdraw.
We are seeking new authors to develop a new protocol which would serve to update the existing review and incorporate the latest
evidence into a new Cochrane Review. However, we would suggest that the current topic is too broad and would therefore recommend
reassessing the title prior to registration. Please contact PaPaS if you are interested: http://papas.cochrane.org/contact-us.
INDEX TERMS
Medical Subject Headings (MeSH)
Enteral Nutrition; Parenteral Nutrition; Bone Marrow Transplantation [ adverse effects]; Fluid Therapy [methods]; Glutamine
[administration & dosage]; Length of Stay; Malnutrition [etiology; prevention & control]; Randomized Controlled Trials as Topic
MeSH check words

Humans

79

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Nutrition support for bone marrow transplant patients

Nutrition support for bone marrow transplant patients (Review)

Nutrition support for bone marrow transplant patients (Review)

Nutrition support for bone marrow transplant patients

PLAIN LANGUAGE SUMMARY

the first option of nutrition support to BMT patients (Weisdorf

Nutrition support for bone marrow transplant patients (Review)

Criteria for considering studies for this review

Types of outcome measures

Hospital duration e.g. mean duration admission to

Nutrition support for bone marrow transplant patients (Review)

Vomiting - mean number of days patients had >/= than 3

Search methods for identification of studies

Data collection and analysis

between review authors extracted results were resolved by discussion.

Correspondence with authors

Nutrition support for bone marrow transplant patients (Review)

Two other studies were separate interventions and could not be

Risk of bias in included studies

Parenteral nutrition versus enteral nutrition

Nutrition support for bone marrow transplant patients (Review)

reduced by 6.62 days (weighted mean difference) with 95% CI

diet and or intravenous hydration. However at 5 years post BMT

Nutrition support for bone marrow transplant patients (Review)

1998 included 251 participants, it would have been beneficial if the

Implications for research

Nutrition support for bone marrow transplant patients (Review)

Professor PR Schloerb and Dr CH Poynton kindly

References to studies included in this review

VM Aquino, AR Harvey, JH Garvin, KT Godder, ML

Jebb 1995 {published data only}

Nutrition support for bone marrow transplant patients (Review)

of different parenteral nutrition regimens in patients

Roberts S, Miller J, Pineiro L, Jennings L. Total parenteral

Santos P, Lourenco R, Camilo ME, Oliveira AG, Figueira

Journal of Parenteral and Enteral Nutrition 1993;17(5):

References to studies excluded from this review

Szeluga 1987 {published data only}

Ford 1992 {published data only}

Takatsuka 2002 {published data only}

Takatsuka H, Takemoto Y, Iwata N, Suehiro A, Hamano

Hopman 2003 {published data only}

Weisdorf 1987 {published data only}

Klein 1994 {published data only}

Young 1993 {published data only}

Lipman 1991a {published data only}

Nutrition support for bone marrow transplant patients (Review)

Mercadante 1998a {published data only}

Schied 2004 {published data only}

Nutrition support for bone marrow transplant patients (Review)

Indicates the major publication for the study

Nutrition support for bone marrow transplant patients (Review)

Characteristics of included studies [ordered by study ID]

Randomised controlled trial

There were no losses to follow up.

Support for judgement

Allocation concealment (selection bias)

Randomised controlled trial.

Nutrition support for bone marrow transplant patients (Review)

Follow up:195 recruited, 2 withdrew

Support for judgement

Allocation concealment (selection bias)

Randomised controlled trial.

120 CHILDREN recruited

Murray & Pindoria-2014

Murray & Pindoria-2014