ONC: Hematopoietic Cell Transplant (2006)

Study Design:
- 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


  • 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





Summary of Results:



Treatment Group

Measures and confidence intervals

Control group

Measures and confidence intervals

Statistical Significance of Group Difference


28.7 +/- 8.8 25.4 +/- 4.3 NS

Days to engraftment

 12.4 days

 12.4 days


Incidence of infection





Days on antibiotics

20.8 +/- 6.6 17.7 +/_ 4.5 0.045

Days of fever

 10.2 +/_ 6.4

 8.0 +/- 6.0


Change in total bilirubin

 18.8 +/_ 29

 11.9 +/- 6.8


Liver function tests

 alkaline higher; SGPT lower; GGT higher    sig

Calorie intake

 88% needs met

 56% needs met


Protein intake

 68% needs met

 39% needs met


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%


Handgrip strength

 decrease 2%

 decrease 6%


Triceps skinfold

 decrease 6%  decrease 5%  0.82


 decrease 2%

 decrease 7%


Serum albumin, Day 30

 35 +/- 6

 38 +/- 5


Days on TPN

 17.5 +/- 7.4  5.3 +/- 5.9  ??

Sense of well-being

 129.9 +/- 16.3

 139.4 +/- 31.9


Survival at 2 years




Nutrition status: intact of depleted

Unknown Unknown 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:
Meredith Corporation
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? ???