EAL

ONC: Hematopoietic Cell Transplant (2006)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

After high-dose chemotherapy and hematopietic cell transplantation (HCT) nutrition problems are common. Oral intake is minimal for several weeks post transplant. Use of TPN is common in this post transplant period. Objective of the study was to compare clinical and nutritional outcomes, well-being measures, and survival in breast cancer (CA) patients undergoing HCT that either receive OD or prophylactic TPN.

Inclusion Criteria:

Stage II-IV breast CA
Female
Receiving HCT
Well nourished upon admission for HCT (> or = 90% IBW or UBW, absence of recent wt loss or poor oral intake, serum albumin > or = 30 g/dL);

There was no statement of how many were excluded.

Exclusion Criteria:

Did not meet well nourished criteria at admission to study

Description of Study Protocol:

Recruitment: No statement of how recruiting was done, or who did the recruiting

Design: Randomized clinical trial with subjects randomized to either OD or TPN; no mention as to how the randomization was done

Blinding used (if applicable): No mention of blinding

Intervention:

Kcal need was determined using Harris-Benedict equation and protein need was set at 1.5 - 1.75 g/kg b wt; used adjusted body wt if "significantly" over IBW
OD group: Standard iv fluids of either 5% dextrose or normal saline; given TPN if oral intake fell below 40% of need for 10 consecutive days, wt loss of 10% of admission wt, need for mechanical ventilation.
TPN group: TPN started day before HCT (day -1); also give iv fluids; TPN was 3-in-1 admisture (final concentration17.5% dex, 5% aa, 10% lipid) 3 times/wk and other 4 days 2-in-1 formula (25% dextrose, 5% aa, final concentration); vitamins and minerals added daily
Both groups allowed to eat ad libitum
TPN discontinued when oral intake > or = to 50% of nutrient need for 2 consecutive days

Statistical Analysis:

Intent-to-treat principles applied
T-test evaluated differences between groups
- Age
- Days to engraftment
- LOS
- Days on antibiotics
- Days of fever
- Body wt changes
- Days on TPN
- Number of days until oral intake >66% of need
- Nutrient intake
Repeated measures analysis of variance
- Changesin triceps skinfold
- Midarm muscle circumference
- Serum albumin
- Total bilirubin
- LFTs
- HGS
- Sense of well-being
Survival analysis using Kaplan-Meier plots
No mention of level of significance used

Data Collection Summary:

Timing of Measurements:

Pt characteristics at baseline
Clinical outcomes -- not stated when measured
Nutrition outcomes measured at admission to +30 days post tx
Sense of well-being was measured admission, discharge (no day mentiond so assume variable) and +30 days post tx
Survival was > or = to 1 year post tx.

Dependent Variables

Variable 1: LOS - days in hospital from initial hospitalization
Variable 2: Days to engraftment (not stated how measured) (ANC > 500)
Variable 3: Incidence of infection determined by positive blood culture
Variable 4: Days on antibiotics - not stated how measured
Variable 5: days of fever - > or = 100.5 F
Variable 6: changes in total bilirubin - not stated how measured
Variable 7: liver function tests - not stated how measured
Variable 8: calorie intake - not stated how measured
Variable 9: protein intake - not stated how measured
Variable 10: number of days until oral intake met 66% of nutrient needs
Variable 11: body wt - not stated how measured
Variable 12: handgrip strength - not stated how measured
Variable 13: triceps skinfold - not stated how measured
Variable 14: midarm muscle circumference - not stated how measured
Variable 15: serum albumin - not stated how measured
Variable 16: days on TPN - not stated how measured
Variable 17: sense of well-being measured using the Profile of Mood States (POMS); no info about realiability or validity
Variable 18: survival for 1 year or more post treatment
Variable 19: nutrition status - intact vs depleted

Overall poorly defined variables with little information how how measured or how operationalized.

Independent Variables: Assigned to oral intake only (OD) or TPN only. Also created a third group of pt who were randomized to the OD and ultimately placed on TPN and called the delayed TPN (DTPN) group

Control Variables: Age, stage of disease, source of HCT (marrow or peripheral blood), number of pt given TPN

Description of Actual Data Sample:

Initial N: 55 females

Attrition (final N): 55 females; no attrition info addressed in the article

Age: 42 y for TPN and 46 y for OD; no info on DTPN group

Ethnicity: no info provided

Other relevant demographics: breast cancer stage TPN = 13 in stage II and III; 14 in stage IV. OD group 10 in stage II and III; 18 in stage IV.

Source of transplant - TPN = 3 peripheral and 24 marrow; OD = 4 peripheral and 24 marrow

no stats done from what I can tell

Anthropometrics: admission TPN wt = 68 kg OD wt = 76 kg

TPN TSF = 29 mm OD TSF = 32 mm

TPN MAMC = 21 cm OD MAMC = 24 cm

TPN HGS = 58 OD HGS = 66

TPN Alb = 31 g/L OD Alb = 32 g/L

Location:

Summary of Results:

Variables	Treatment Group Measures and confidence intervals	Control group Measures and confidence intervals	Statistical Significance of Group Difference
LOS	28.7 +/- 8.8	25.4 +/- 4.3	NS
Days to engraftment	12.4 days	12.4 days	??
Incidence of infection	3	0	0.051

Days on antibiotics	20.8 +/- 6.6	17.7 +/_ 4.5	0.045
Days of fever	10.2 +/_ 6.4	8.0 +/- 6.0	0.19
Change in total bilirubin	18.8 +/_ 29	11.9 +/- 6.8	NS

Liver function tests	alkaline higher; SGPT lower; GGT higher		sig
Calorie intake	88% needs met	56% needs met	<0.001
Protein intake	68% needs met	39% needs met	<0.0001

Number of days until oral intake >66% needs	20.2 +/- 7.4 d	19.9 +/- 6.0 days	0.89
Body weight	decrease 2%	decrease 7%	0.0001
Handgrip strength	decrease 2%	decrease 6%	0.32

Triceps skinfold	decrease 6%	decrease 5%	0.82
MAMC	decrease 2%	decrease 7%	0.05
Serum albumin, Day 30	35 +/- 6	38 +/- 5	0.55

Days on TPN	17.5 +/- 7.4	5.3 +/- 5.9	??
Sense of well-being	129.9 +/- 16.3	139.4 +/- 31.9	NS
Survival at 2 years	74%	57%	0.73

Nutrition status: intact of depleted

Unknown

Author Conclusion:

While prophylactice TPN preserved nutritional status and possibly QOL better than OD, there were no differences found in clinical outcomes or survival.

Prophylactic TPN did result in a more intact nutritional status (no stats) and preservation of lean body mass in TPN but did not impact LOS or survival.

Funding Source:

Industry:

Meredith Corporation

Other:

University/Hospital:

Baylor University Medical Center

Reviewer Comments:

Not much difference and very little information as to how exactly the measures/variables were operationalized. Cox proportional hazard model may have provided better statistical analysis than measures used

Harris-Benedict equation used to determine energy needs

Adjusted body weight was used to determine energy needs if "significantly" over IBW; however, "significantly" is not defined

Cox regression analysis not used

No info on how operationalized nutrient intake; not the best stats for this b/c of differing times by subject

Level of statistical significance not mentioned

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
	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
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
2.	Was the selection of study subjects/patients free from bias?		???
	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?	Yes
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	???
3.	Were study groups comparable?		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?	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
	3.5.	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
4.	Was method of handling withdrawals described?		No
	4.1.	Were follow-up methods described and the same for all groups?	No
	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%.)	No
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	???
	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?		No
	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.)	???
	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
	5.5.	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?		???
	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
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	???
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	???
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	6.6.	Were extra or unplanned treatments described?	???
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	Yes
	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?		No
	7.1.	Were primary and secondary endpoints described and relevant to the question?	???
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	???
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	No
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	???
	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
	7.7.	Were the measurements conducted consistently across groups?	Yes
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		???
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	No
	8.2.	Were correct statistical tests used and assumptions of test not violated?	No
	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)?	???
	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?	No
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	No
9.	Are conclusions supported by results with biases and limitations taken into consideration?		No
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	No
10.	Is bias due to study's funding or sponsorship unlikely?		No
	10.1.	Were sources of funding and investigators' affiliations described?	No
	10.2.	Was the study free from apparent conflict of interest?	???