EAL

ONC: Hematopoietic Cell Transplant (2007)

Citation:

Lough M, Watkins R, Campbell M, Carr K, Burnett A, Shenkin A. Parenteral nutrition in bone marrow transplantation. Clin Nutr. 1990;9:97-101.

Study Design:

Randomized Controlled Trial

Class:

A - Click here for explanation of classification scheme.

Quality Rating:

NEUTRAL: See Quality Criteria Checklist below.

Research Purpose:

To justify whether TPN is needed in the standard care of BMT patients in a small center.

Inclusion Criteria:

All patients admitted for BMT during the study

Exclusion Criteria:

Not indicated

Description of Study Protocol:

Recruitment All patients admitted during the study period (time period and study location not indicated) were randomized to receive TPN or maintenance IV.

Design Patients were randomized at admission by use of pre-sealed envelopes drawn by a nurse. Patients were followed from day of BMT and continued for 21 days. 14 patients received TPN starting on day after BMT which continued for 14 days. 15 patients received IV fluids only. All patients had access to oral diet during the study.

Blinding used: Presealed envelopes were used in randomization to blind practitioners and investigators from study group.

Intervention:

TPN solution consists of 500 cc 50% dextrose for 1000 kcal, 500 cc 20% intralipids for 1000 kcal, 1000 cc 8.5% amino acids for 14 g nitrogen, supplemental RDA of vitamins and minerals, replacement sodium, potassium and magnesium based on individual biochemical analysis and 100 umol of zinc.

IV fluids consisted of 5% dextrose solution and electrolytes as needed.

Statistical Analysis

Wilcoxin signed rank for changes within groups
Mann-Whitney for between group changes
Chi-square for survival comparison between groups

Data Collection Summary:

Timing of Measurements

On admission

7 day dietary recall
Tricep skinfold
Midarm muscle circumference
weight
serum urea
electrolytes
complete blood count
white count with differential
serum albumin
serum transferrin
retinol
liver function tests

Daily

oral intake recorded by nursing and evaluated later by dietitian
serum urea
electrolytes
complete blood count
white count with differential
serum albumin

Twice weekly

serum transferrin
retinol
liver function tests

End of study

tricep skinfold
midarm muscle circumference
weight

Dependent Variables

Tricep skinfold
MAMC
weight
serum urea
electrolytes
complete blood count
white count with differential
serum albumin
serum transferrin
retinol
liver function tests
caloric intake
clinical outcomes including infection, time to engraftment, survival, etc.

Independent Variables

TPN
IV fluids

Control Variables

Description of Actual Data Sample:

Initial N: 29 patients (9 females, 20 males)

Attrition (final N): 25 patients (10 TPN and 15 controls, age and sex not stratified for final analysis)

Age: 14 - 44 years

Ethnicity: not indicated

Other relevant demographics:

Type transplant	Disease	TPN group	Control

Autologous	Acute non-lymphocytic leukemia	6	6

Allogeneic	Acute non-lymphocytic leukemia	5	4
	Acute lymphocytic leukemia	1	3
	Chronic granulocytic leukemia	1	0
	Aplastic anemia	0	2
	non-Hodgkins lymphoma	1	0

Anthropometrics

Weight on admission:

TPN group 58.8 kg +/- 7.7
Control: 65.5 kg +/-19.4

TSF on admission:

TPN group: 15.3 mm +/- 7.4
Control: 13.8 mm +/-7.1

MAMC on admission:

TPN group: 21.6 cm +/-2.6
Control: 23.3 cm +/- 2.9

Differences on admission not statistically analysed.

Location: not indicated by authors from Royal Infirmary, Glasgow UK

Other information:

9 of TPN patients did not receive the prescribed volume or length of TPN in this study due to veno-occlusive disease, refusal, and fluid overload.

Summary of Results:

Findings

Anthropometrics

Both TPN and controls experienced significant decreases in TSF, MAMC and weight during the study period (p<0.001)
Weight loss was significantly greater in control group from baseline to post-transplant (-4.7 kg control versus -2.6 kg TPN group, p<0.05)
Change in TSF and MAMC were not significantly different between groups from baseline to post-transplant

Biochemical

Glucose- no hyperglycemia in the TPN group
Bilirubin- significantly higher in TPN group than controls on both day 14 and 21 (22 umol/l versus 15 umol/l day 14 and 20.5 umol/l versus 15 umol/l day 21).
serum transaminases and alkaline phosphatase NS
serum gamma glutamyl transferase (VGT)- significantly higher in TPN group (p<0.05) on day 21 (47/5 U/l compared to 33.0 U/l)
Albumin- no significant changes for either group pre to post-transplant or between groups and values were WNL
Transferrin- values decreased post transplant for both groups, with a significant decrease in the control group (1.9 g/l to 1.8, p<0.05)
Retinol- values WNL for both groups pre and post transplant, TPN group had a significant decrease (1.7 umol/l to 1.6, p<0.05), while control values increased but not significantly

Clinical support/conditions

No significant difference for red blood cell transfusions between groups
Significantly more fevers in TPN compared to controls (3 versus 1, p<0.05)
Significantly more positive blood cultures in TPN group (8 patients versus 1, p<0.05)
No significant difference for incidence of GVHD
Recovery of white blood cell count was not significantly different between groups
No difference in survival at day 200 post transplant

Caloric /protein intake

Pre-transplant: (mean intake for all patients) 2430 +/- 630 kcal/day and 14.6 +/- 3.5 g Nitrogen/day
During study: (mean daily intake of TPN group from TPN solution) 1367 +/- 398 kcal and 8.0+/- 2.7 gm nitrogen
Mean +/- SD Oral intake during study for TPN and controls

Group	Week 1	Week 2	Week 3	Week 4
Control	765+/- 362	879 +/- 348	978 +/- 513	875 +/- 313
TPN	382 +/- 154	375 +/- 178	484 +/- 248	414 +/-195
p value	<0.001	<0.001	<0.01	<0.001

Oral intake during study as a result of BMT was significantly less (p<0.001) than preBMT

Author Conclusion:

This study was limited by the discontinuation of TPN in 7 patients secondary to fluid overload.

The TPN group experienced elevated bilirubin, VGT and more episodes of pyrexia and positive blood cultures. However TPN did not impact time to grafting, survival or incidence of GVHD.

TPN patients in this study only received 80% BEE based on HBE. The authors cite the small sample size and less aggressive approach to nutrition therapy as factors that hinder the ability to draw conclusions related to the use of TPN and its effect on survival.

TPN should be used with caution in smaller BMT clinics. Further studies are needed.

Funding Source:

University/Hospital:

Royal Infirmary

Reviewer Comments:

This study does show the impact of BMT on oral intake (caloric and protein) as compared to preBMT and effect of TPN on tolerance, recovery and complications from BMT.

Limitations:

patients inability to take prescribed TPN dosage
mixed transplant types
small sample size
limited characteristics of patients included
limited information on location of study and time frame of study
no information on transplantation regimen, other medications, etc.
no clear inclusion/exclusion criteria
did not use intent to treat analysis

Quality Criteria Checklist: Primary Research
Relevance Questions
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	Yes
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	Yes
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
	1.	Was the research question clearly stated?	Yes
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	No
	1.3.	Were the target population and setting specified?	No
	2.	Was the selection of study subjects/patients free from bias?	No
2.	Was the selection of study subjects/patients free from bias?		No
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	No
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	No
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	No
	2.3.	Were health, demographics, and other characteristics of subjects described?	No
	2.4.	Were the subjects/patients a representative sample of the relevant population?	???
	2.4.	Were the subjects/patients a representative sample of the relevant population?	???
	3.	Were study groups comparable?	???
3.	Were study groups comparable?		???
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	Yes
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	Yes
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	???
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	???
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	Yes
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	Yes
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	N/A
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	N/A
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	N/A
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	N/A
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
	4.	Was method of handling withdrawals described?	Yes
4.	Was method of handling withdrawals described?		Yes
	4.1.	Were follow-up methods described and the same for all groups?	Yes
	4.1.	Were follow-up methods described and the same for all groups?	Yes
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	Yes
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	Yes
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	No
	4.4.	Were reasons for withdrawals similar across groups?	No
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
	5.	Was blinding used to prevent introduction of bias?	Yes
5.	Was blinding used to prevent introduction of bias?		Yes
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	???
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	???
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	Yes
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	Yes
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	N/A
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	N/A
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	N/A
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	N/A
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
	6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?	Yes
6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?		Yes
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	Yes
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	Yes
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	N/A
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	N/A
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	Yes
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	Yes
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	Yes
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	Yes
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	No
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	No
	6.6.	Were extra or unplanned treatments described?	N/A
	6.6.	Were extra or unplanned treatments described?	N/A
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	N/A
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	N/A
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
	7.	Were outcomes clearly defined and the measurements valid and reliable?	Yes
7.	Were outcomes clearly defined and the measurements valid and reliable?		Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	Yes
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	Yes
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	Yes
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	7.5.	Was the measurement of effect at an appropriate level of precision?	Yes
	7.5.	Was the measurement of effect at an appropriate level of precision?	Yes
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	Yes
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	Yes
	7.7.	Were the measurements conducted consistently across groups?	Yes
	7.7.	Were the measurements conducted consistently across groups?	Yes
	8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?	Yes
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		Yes
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	No
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	No
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	No
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	No
	8.6.	Was clinical significance as well as statistical significance reported?	Yes
	8.6.	Was clinical significance as well as statistical significance reported?	Yes
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	N/A
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	N/A
	9.	Are conclusions supported by results with biases and limitations taken into consideration?	Yes
9.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	Yes
	9.2.	Are biases and study limitations identified and discussed?	Yes
	10.	Is bias due to study's funding or sponsorship unlikely?	Yes
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes