EAL

ONC: Nutrition Status and Outcomes in Adult Oncology Patients (2013)

Citation:

Eriksson KM, Cederholm T, Palmblad JE. Nutrition and acute leukemia in adults: Relation between nutritional status and infectious complications during remission induction. Cancer. 1998; 82: 1,071-1,077.

PubMed ID: 9506351

Study Design:

Retrospective Cohort Study

Class:

B - Click here for explanation of classification scheme.

Quality Rating:

NEUTRAL: See Quality Criteria Checklist below.

Research Purpose:

To evaluate whether variables reflecting nutrition would be related to infections and neutropenia in adult patients with acute leukemia who were undergoing induction therapy for first remission. Significance of various infections and total parenteral nutrition was also assessed.

Inclusion Criteria:

Initially randomized to receive anti-leukemic and anti-infectious treatments in 1980 to 1984
Evaluable with regard to infectious complications
Full medical record available.

Exclusion Criteria:

Incomplete or unavailable medical record.

Description of Study Protocol:

Recruitment

Study was part of a multi-center trial of anti-leukemic and anti-infective treatments conducted according to protocols adopted by the Leukemia Group of Middle Sweden, recruitment details not discussed.

Design

Subjects were obtained from a larger multi-center trial of anti-leukemic and anti-infective treatments. Subjects who were initially randomized to receive anti-leukemic and anti-infectious treatments and had full medical records available were eligible for the study. Various anti-leukemic treatments were, by stratification, also combined with prophylactic administration of acyclovir, ketoconazole, a combination of these or placebo. Neutropenia and infections were documented throughout study. Patients were followed with serial measurements, obtained weekly when possible, of body weight, body mass index, serum concentrations of albumin, days and weeks with diarrhea and weeks of total parenteral nutrition. The duration of neutropenia, various infections and fevers were related to changes in body weight and serum albumin concentrations as well as total parenteral nutrition.

Statistical Analysis

Correlation analyses were performed by calculating the Pearson's and Spearman's correlation coefficients according to the type of distribution of the data of a given variable
Multivariate tests were run by means of stepwise multiple regression analyses to assess the impact of selected variables on outcome
Question of whether prophylaxis with acyclovir or ketoconazole might have influenced the nutritional state could not be analyzed in retrospect because that was not an aim of that trial and patients were not stratified according to nutritional state.

Data Collection Summary:

Timing of Measurements

Serial measurements, obtained weekly if possible, of body weight, body mass index, serum concentrations of albumin, days and weeks with diarrhea and weeks on total parenteral nutrition
Timing of measurements of body temperature and blood neutrophil counts were not described.

Key Study Variables

Body weight in kilograms
Body mass index in kg/m²
Serum albumin concentrations in g per L
- Normal values: More than 35g per L
- Subnormal values: 25 to 35g per L
- Low values: Less than 25g per L
Time spent with diarrhea in percentage of induction treatment time
Weeks on total parenteral nutrition
Days spent with neutropenia:
- Severe neutropenia defined as blood neutrophil counts less than 0.1 x 10⁹ per L
Number of infections per patient
Number of fever episodes and days spent with fever:
- Fever defined as body temperature more than 38.5 degrees Celsius once or more than 38 degrees Celsius twice during a 12-hour period.

Control Variables

Infection-related mortality.

Description of Actual Data Sample:

Initial N: 107 patients randomized to receive anti-leukemic and anti-infectious treatments; 52 patients eligible for study
Attrition (final N): 52 patients (29 males and 23 females)
Age: Mean 52 years (range 15 to 74 years)
Other relevant demographics: 46 patients with acute non-lymphocytic leukemia and six patients with acute lymphatic leukemia.

Anthropometrics

BMI at admission with new acute leukemia diagnosis was 23.6+4.0kg/m² (range 17.5 to 34.5kg/m²) for males and 23.3+2.9kg/m² (range 17.1 to 27.8kg/m²) for females
During the induction period, patients lost a mean of 5.1kg of body weight corresponding to -1.8 BMI units
In the subset of patients who lost more than 2kg (80% of patients), the mean loss was 6.8kg
No significant weight loss or weight gain was observed in eight patients.

Location

Multi-center trial in Sweden.

Summary of Results:

Key Findings

Neutropenia and infections:
- Patients spent 27% of the induction time with profound neutropenia and a similar proportion of that time with fever
- Relative and absolute neutropenia time periods correlated statistically with the relative and absolute time periods with fever (R=0.31, P=0.026 and R=0.59, P=0.001)
- Positive correlations for neutropenia time and numbers of fever episodes, infections and of bacteremias (P<0.001 for all correlations)
- The longer patients were neutropenic, the more infections were found and the longer and more severe the infections were.
Weight and BMI changes:
- Change in weight were statistically significantly related to the number of days with fever (R=-0.35, P=0.026)
- No significant correlation between this nutritional variable, or the initial or lowest BMI and the number of infections or bacteremias (R=0.03 to 0.16, P>0.05 for all these analyses)
- No statistically significant relation was observed between the maximal weight or BMI changes or the lowest BMI recording and the days or relative time spent with neutropenia (R=0.5 to 0.26, P>0.05 for all these correlations).
Serum albumin concentrations:
- During remission induction, nearly half of patients (47%) developed severe hypoalbuminemia
- In this subset of patients, severe hypoalbuminemia prevailed for 34% of induction time compared to mean value of 16% for all patients
- Relative time spent with severe hypoalbuminemia correlated positively with relative and absolute time with fever (R=0.71, P=<0.001 and R=0.33, P=0.033)
- Lowest recorded serum albumin value correlated well but negatively with number of infections and number of days with fever (R=-0.33, P=0.03 and R=-0.45, P=0.002)
- Correlations observed for maximal change of serum albumin concentration and days with fever (R=0.43, P=0.004)
- Neither time spent with neutropenia nor the number of infections related to the time spent with severe hypoalbuminemia (R=-0.15 and 0.11, P>0.05).
Diarrhea:
- Positive correlations between the proportions of time spent with diarrhea and time spent with fever and hypoalbuminemia; the longer time spent with diarrhea, the longer time was also spent with fever (R=0.33, P=0.02) and severe hypoalbuminemia (R=0.34, P=0.03)
- No statistically significant relation between time spent with diarrhea and changes in weight (P>0.05).
TPN:
- TPN was given to 33% of patients who received TPN for 21% of induction period
- Patients with severe hypoalbuminemia and prolonged time with fever (but not time with neutropenia) spent more time with TPN (R=0.60 and 0.69, P<0.001 for the two variable sets)
- Weight changes or time with diarrhea did not correlated with TPN time
Multiple regression analysis:
- When days with fever was chosen as dependent variable, days with severe neutropenia and change in serum albumin levels were strongly associated predictors (R=0.57 and 0.70, P=0.0004 and 0.003)
- Weight loss did not appear to be an independent risk factor for infection when the latter was expressed as days with fever
- When analysis was performed using change in weight as dependent variable, regression model chose change in serum albumin levels as the only independent variable (R=0.37, P=0.03).

Variables	Values at Admission	Mean Change or Mean Time
Body weight, kg	69.9±12.8	-5.1±4.8
BMI	23.5±3.5	-1.8±1.7
Serum albumin concentration, g per L	34±6	-9±6
Mean time (days) spent with serum hypoalbuminemia more than 35g per L, as % of induction treatment time		15±23
Mean time (days) spent with serum hypoalbuminemia 35g to 25g per L, as % of induction treatment time		69±27
Mean time (days) spent with serum hypoalbuminemia less than 25g per L, as % of induction treatment time		16±23

Other Findings

Patients received approximately 2.5 courses of cytotoxic treatment over an average of 71 days
Remission rate was 63%
15 patients died, seven of whom died of infections.

Author Conclusion:

This study demonstrates that adult patients with acute leukemia undergoing intensive cytotoxic treatment for induction of first remission often have moderate weight loss and a high incidence of severe hypoalbuminemia, indicating a negative protein-energy balance. The presence of weight loss and severe hypoalbuminemia were closely related to the duration of patients' infections.

Funding Source:

University/Hospital:

Karolinska Institutet

Not-for-profit

Swedish Medical Research Council

Reviewer Comments:

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?		N/A
	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?	N/A
	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?	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?	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?		No
	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.)	No
	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?		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?	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?	No
	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)?	Yes
	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?	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