ONC: Hematopoietic Cell Transplant (2006)

Study Design:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:

The purpose of this pilot investigation was

1)  to determine if the medical records of hematopoietic stem cell transplant patients could be accurately reviewed for TPN exposure, hyperglycemia, infection, in-hospital mortality, and

2) to provide preliminary data on observed associations between TPN exposure to the incidence of hyperglycemia and various proxies of morbidity.

Inclusion Criteria:

* Patients 18 years of age or older.

* Admitted for an initial autologous or allogeneic hematopoietic stem cell transplant.

* Patients who had not previously received home TPN.

* Without acute infection at time of admission.

Exclusion Criteria:

* Patients who received less common types of hematopoietic stem cell tranplant (e.g., matched unrelated donor, syngeneic, and umbilical cord).

* Patients who received a prior hematopoietic stem cell transplants or  those who received a prior hematopoietic stem cell cell transplant.

* Individuals with a history of home TPN.

* Those admitted with an existing infection.

Description of Study Protocol:

Recruitment :  N/A


Design :  Retrospective cohort


Blinding used (if applicable):  N/A


Intervention (if applicable):  N/A


Statistical Analysis

*  Variables that were not normally distributed were log transformed.

*  If normality could not be achieved, analysis used nonparametric tests.

*  Descriptive statistics were calculated.

*  Chi-square analysis used to detect differences in dichotomous variables.

*  Student t test to detect differences in means that were normally distributed.

*  Wilcoxon rank-sum tests used to detect diffferences in means that were not normally distributed


Data Collection Summary:

Timing of Measurements:  Measurements collected from medical record.


Dependent Variables

  • Incidence of hyperglycemia, from laboratory reports
  • Infection, from laboratory reports ( data of infection, source, and infectious agnet)
  • In-hospital mortality  (Alive/dead) at discharge from physician progress note
  • Morbidity: 

           - Length of stay, from medical record

           - Number of red blood cell and platelet transfusions, verified from physician progress notes, nursing progress notes and blood bank summaries. 

          -  Engraftment time, defined as number of days between transplant day 0 and the first day of 3 consecutive days that the absolute neutrophil count was more than 0.5 X 109/L.

          -  Medication use and duration 

          -  Neutropenic fevers

  • Nutritional status:

             -  Height, weight, BMI, percent ideal body weight determined at admissions

             -  Weight assessed daily from nursing progress notes

             -  Serum albumin assessed at admission (less than 35 g/L based on clinical relevancy.

  • Mortality


Independent Variables:  TPN exposure (TPN vs. No-TPN) verified from initial nutrition evaluation or from pharmacy records.


Control Variables:  None specified.


Description of Actual Data Sample:


Initial N: 48 records met inclusion criteria from review of 59 records. 

                Males: n=28, 58%; Females: n=20, 42%.


Attrition (final N): NA

Age: Mean (+SD)=48.2 (13.4)

*  The age of No-TPN group was significantly higher (52.9+13.0) than the TPN (45.4+13.0)

Ethnicity: White, n=23 (48%); African American: n=20 (39.5%); Hispanic: n=6 (12.5%)

Other relevant demographics:


                                                                          TPN (n=30)                    No-TPN (n=18)

*          BMI                                                         28.7+ 8.2                         31.2+8.2 

*         % Ideal body weight                                  127%                             140%                            

Location: Records reviewed were from two institutions in Chicago, IL, USA:  Rush Presbyterian St. Luke's Medical Center (Rush) or the University of Illinois Medical Center (UIC)


Summary of Results:

TPN Characteristics by hospital

                                    Rush                UIC               Overall
                                   (n=24)            (n=6)

Days of TPN                10.9+6.6         6.7+2.9             10.2+7.0
Days until TPN             11.0+3.0       12.0+1.8            11.0+3.0
Total kcal                  1,903+413     1,508+562         1,824+464
kcal/kg                         27+4              20*+7
Protein (g/kg)             1.4+0.3          1.2*+0.3
Lipid emulsion type                  N
   10%                            0                        1
    20%                         23                         4               
    None                           1                        1

Hyperglycemic events and days before and after TPN administration

                                                           TPN (Yes)                                             TPN (No)
                                                 Rush beforea          Rush afterb             Rush before       Rush after
                                                    (n=24)                   (n=24)                     (n=8)               (n=8)     
Number of hyperglycemic
eventsc                                       6.2+3.4                  6.2+3.7                 6.1+3.0             2.2*+3.3
Proportion hyperglycemic
days (%)c,d                                56.1+28.7              56.1+33.7            55.6+27.4         20.2*+30.0
median                                          59.0                        72.7                     54.5                     9.1
Range                                          0-100                      0-100                 18-100                   0-91


                                                  UIC before            UIC after                UIC before        UIC after
                                                       (n=6)                  (n=6)                     (n=9)                  (n=9)    
Number of hyperglycemic
eventsc                                       6.2+4.1                  5.5+1.8                  5.7+3.0            2.8*+2.5
Proportion of hyperglycemic
days (%)c,d                               51.4+34.3            78.6+25.1               47.2+25.0         39.7*+36.3
median                                         41.7                        85.7                        50.0                  28.6
Range                                         17-92                     43-100                     17-92               0-100

a The mean number of days prior to TPN initiation was 11 days at Rush and 12 days at University of Illinois Medical Center (UIC). "Before" represents the 11 days and 12 days from hospital admission until TPN was started at Rush and UIC, respectively.
b "After" represents the standardized time period during which TPN was infused at each hospital based on the mean; or 12 to 22 days and 13 to 18 days for TPN and non-TPN recipients at Rush and UIC, respectively.
c Plus-minus values are means+standard deviation
d Proportion of hospital days that glucose > 6.1 mmol/L during actual or simulated TPN timeframe.
*P<.05, differaence between groups.

Other clinic characteristics by institution and TPN status

                                              Rush                   UIC                   TPN                   No TPN
RBC transfusions                  4.7+4.7               2.1+1.8*          5.0+4.5               2.1+2.9*
                                              (n=33)                (n=15)              (n=30)                (n=18)

Platelet transfusions            5.1+4.7               1.4+1.6*          5.1+4.9               2.1+2.2
                                              (n=33)                (n=15)              (n=30)                (n=18)

Engraftment time(days):
  Autologous                       13.0 (n=21)         10.0*(n=14)    12.0 (n=21)        11.0 (n=14)      
  Allogeneic                         12.0 (n=9)           12.0 (n=1)       12.0 (n=9)          11.0 (n=3)

Neutropenic fever n (%)        31 (94)              13 (87)                27 (56)           17 (35)

Febrile days (%)a,b            24.0+15.4            15.0+13.0*        20.2+16.1        19.9+13.5
                                            (n=33)                   (n=15)              (n=30)            (n=18)
Antibiotic usage (days)a      7.1+4.8                 6.3+5.0            7.4+4.4            5.9+4.4
                                            (n=33)                   (n=15)              (n=30)            (n=18)
  Mean                               0.79+0.86            0.53+0.74        0.77+0.90        0.61+0.70
  Median                                  1.0                        0                        0.5                1.0

Repeat cultures (n)                 3                           0                        3                    0   

a Mean+standard deviation
b Proportion of total hospital days with a temperature > 38oC (100.4oF)  
*P<.05, difference between institution or TPN category.     

Other Findings

 *  There were no significant differences between institutions regarding patient demographics or number of CD34+ cells transplanted.

*   Patients at UIC had significantly better admission nutritional status as crudely assess by overall BMI (P=.002), admission albumin levels (P=.03) and percent ideal body weight. 

*  Patients at Rush had significantly longer lengths of stay (P=.03) and higher daily hospital charges (P=.0001)

*  Conditioning regimen differed with regard to rituximab use at Rush, and with an unequal number of TPN patients receiving only melphalan and total body irradiation with cyclophosphamide.

*  63% (n=30) of patients received TPN during transplant:  73% (n=24) at Rush and 40% (n=6) at UIC.

        -  TPN recipients (vs no-TPN) were significantly younger (P=.05), had significantly more expensive daily hospital charges (P=.0004), longer lengths of stay (P=.0005), and lower percent ideal body weight at admission (P=.05).

       -  No significant differences between TPN and No-TPN for BMI, admission albumin, admission fasting glucose, or mortality.

* In-hospital mortality differences were not detected between TPN groups.


Author Conclusion:
Hematopoietic stem cell transplant patients who received TPN had a greater incidence of hyperglycemia when compared with hematopoietic stem cell transplant patients who received standard nutrition care.  However, these findings were limited by small sample size.    For now, dietitians encountering hematopoietic stem cell transplant patients receiving TPN should focus on routine blood sugar monitoring, overall better blood sugar control, and investigations that could potentially support evidenced-based protocols to determine appropriate TPN candidates.
Funding Source:
University/Hospital: University of Illinois Chicago, University of Chicago
Reviewer Comments:
One important limitation of this study, as discussed by the authors,  is the small sample size.

This study also achieved its objective to determine if data from medical records was accessible and available:  patient records were easily obtainable at both institutions and the primary variables of interest were available and verifiable.
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? Yes
  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) N/A
  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.) 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? Yes
  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? N/A
  4.1. Were follow-up methods described and the same for all groups? N/A
  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%.) N/A
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? 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? N/A
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? N/A
  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.) N/A
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? No
  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? Yes
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? N/A
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? 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
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? Yes
  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? 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? 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
  7.3. 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
  7.5. Was the measurement of effect at an appropriate level of precision? Yes
  7.6. Were other factors accounted for (measured) that could affect outcomes? ???
  7.7. Were the measurements conducted consistently across groups? ???
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
  8.2. 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
  8.4. 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)? N/A
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? N/A
  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
9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? Yes
10. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes