EAL

ONC: Hematopoietic Cell Transplant (2006)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To compare clinical and nutritional effects of glucose based total parenteral nutrition with lipid based total parenteral nutrition in patients undergoing allogeneic bone marrow transplantation

Inclusion Criteria:

- undergoing non-T-depleted allogeneic bone marrow transplantation
   for either
                 •chronic myeloid
                 •acute myeloid
                 •acute lymphoid leukemia
                 •other hematologic malignancies

Exclusion Criteria:

Not indicated

Description of Study Protocol:

Recruitment - 66 consecutive allogeneic bone marrow transplantation patients with hemologic maglignancies

Design - patients were randomly assigned to either 100% glucose-based total parenteral nutrition (TPN) or 80% lipid-based TPN administered from day 1 to day 15 after bone marrow transplantation (BMT). Time to engraftment (EGT), incidence of sepsis, metabolic complications (hyperglycemia and hypertriglyceridemia), incidence of acute graft-versus-host disease (A-GVHD) and relapse, survival at 18 months, incidence of deaths for A-GVHD and relapse were evaluated.

Blinding used (if applicable) -No blinding

Intervention (if applicable) - 100% glucose based TPN or 80% lipid based TPN

Statistical Analysis

- Student's t test for paired and unpaired data

- x2 and Fisher's exact test for differences among proportions

- the product-limit method for censored data to evaluate the differences in survival

- Mantel-Cox and Breslow (log-rank) tests for differences in survival

- P<0.05

- mulitvariate analysis performed using the Cox proportional hazards regression model to evaluate the independent contribution of potentially confounding variables

Data Collection Summary:

Timing of Measurements

Clinical events evaluated within 100 days after BMT:

•rate and time (days) to engraftment of polymorphonuclear cells (PMNs) and platelets (PLTs) as determined by blood cell count (PMN >500/cmm; PLT >25,000/cmm)

•metabolic complications such as

- hyperglycemia (as defined by at least two episodes of blood glucose >10 mmol/L which could be controlled by increasing insulin dose)

- hypertriglyceridemia (>2.82 mmol/L

•infectious complications (bacterial and fungal infections)

•occurrence of acute graft-versus-host disease

Clinical events evaluated within 18 months after BMT:

•occurrence of chronic GVHD

•rate of disease relapse

•time to relapse

•mortality rate

•cause of death

Before starting TPN and daily until TPN withdrawal:

•Serum concentrations of

- urea nitrogen

- glucose

- sodium

- potassium

- calcium

Monitored three or four times per day in patients with tendency toward abnormally elevated blood glucose:

•blood and urine concentrations

Before starting TPN and weekly until TPN withdrawal:

•Serum concentrations of

- cholesterol

- triacylglycerol

- phosphorous

- magnesium

-alanine aminotransferase

- aspartate aminotransferase

- total bilirubin

Nutritional status evaluated at day 0 and day 15 after BMT by means of anthropometric indices:

•BW

•triceps skinfold thickness

•mid-arm circumference

•body weight

Dependent Variables

Bone Marrow Engraftment
Infectious Complications
Metabolic Complicatons
Acute GVHD Incidence
Lethal Acute GVHD
Death

Independent Variables

• Energy substrates (100% glucose based vs 80% lipid based TPN)

Control Variables

•TPN contained 146.3K/kg/day + 1.4g of prot/kg/day given as amino acids

•Conditioning regimens (radiation and chemotherapy)

•Prophylaxis and treatment of GVHD

•Prohylaxis of septic complications

•1 U of insulin/10g of glucose

Description of Actual Data Sample:

Initial N: 66 (39 men, 27 women)

Attrition (final N): 60 (29 lipid, 31 glucose)

Age: Glucose group: 15-47 years, Lipid group: 16-44 years

Ethnicity: Not indicated

Other relevant demographics:Both groups comparable for age, sex, diagnosis, donor parity, sex mismatch, HLA matching, cytomeglavirus serological status, antineoplastic treatment and radiation dose.

Anthropometrics

Anthropometric indices were within normal range before starting TPN and no significant changes in body weight, skin fold thickness and mid-arm circumference were recorded after 15 days of TPN in either group.

Location:Italy

Summary of Results:

Hyperglycemia
- Lipid based group (3.4%) vs. Glucose based group (32%) P=0.004

Death (due to A-GVHD)
- Lipid based group (0) vs Glucose based group(5) P<0.05

Survival at 18 months
- Lipid based group (62%) vs Glucose based group(42%) NS

No difference between lipid and glucose based groups:
- rate of bone-marow EGT
- time to EGT
- incidence of sepsis and fungal infections during TPN
- incidence of A-GVHD
- rate of relapse at 18 months

Author Conclusion:

Supplementation after allogeneic bone marrow transplantation with lipid-based TPN, but not glucose-based TPN, is associated with lower incidence of lethal A-GVHD and metabolic complications and may be of benefit to patients undergoing allogeneic bone marrow transplantation for hematologic maglinancies. More studies are needed in order to better understand the results.

Funding Source:

Not-for-profit

Foundation associated with industry:

Reviewer Comments:

Limitations:

- Was not disclosed from where the patients were randomly chosen from

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?	Yes
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)	No
	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?		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
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	Yes
	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
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	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
	5.4.	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?		N/A
	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?	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?	Yes
	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?	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
	8.1.	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)?	No
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	Yes
	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?	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