EAL

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

Citation:

Iversen PO, Wisløff F, Gulbrandsen N. Reduced nutritional status among multiple myeloma patients during treatment with high-dose chemotherapy and autologous stem cell support. Clin Nutr. 2010 Aug; 29(4): 488-491.

PubMed ID: 20044183

Study Design:

Prospective Cohort Study

Class:

B - Click here for explanation of classification scheme.

Quality Rating:

NEUTRAL: See Quality Criteria Checklist below.

Research Purpose:

To use anthropometrical methods combined with measurements of biomarkers to prospectively determine the nutritional status among unselected multiple myeloma patients undergoing intensive treatment. They also examined if nutritional status was associated with health-related quality of life (HRQoL) scores.

Inclusion Criteria:

Unselected and newly diagnosed, previously untreated, multiple myeloma patients referred to a hospital in Oslo, Norway for intensive treatment including high-dose melphalan with autologous blood stem cell transplantation during a consecutive two-year period starting February 1, 2004. All patients were in stage II and presented with symptomatic multiple myeloma.

Exclusion Criteria:

Not described.

Description of Study Protocol:

Design

Prospective cohort study.

Intervention

Treatment to six patients consisted of three courses with a four-week interval using a combination of vincristine (1.6mg) and doxorubicin (36mg per m²) for four days, and 40mg of dexamethasone daily for days one to four, days nine to 12 and days 17 to 20. This regimen regimen was replaced in September 2005 with a combination of cyclophosphamide (1g per m²) day one and 40mg of dexamethasone days one to four and days nine to 12; this CyDex regimen was given twice with a three-week interval to nine patients. Both treatments gave similar results on nutritional status so data are pooled.
Autologous stem cells were harvested 10 days after a dose of cyclophosphamide (2g per m²) and daily injections of granulocyte colony-stimulating factor (5mcg per kg). Patients received a high-dose of melphalan (200mg per m²) followed by autologous stem cell infusion two days later. Patients received antimicrobial treatment (200mg acyclovir daily and trimethoprim 80mg plus sulfamethoxazole 400mg every weekend) for three months after therapy.

Statistical Analysis

Differences were evaluated with Kruskal-Wallis test followed by Dunn's multiple comparison test to analyze possible differences at selected time points compared with baseline levels. P<0.05 was considered significant.

Data Collection Summary:

Timing of Measurements

Measurements were conducted at:

Diagnosis before treatment
After the final VAD/CyDex treatment
Immediately prior to high-dose melphalan
After bone marrow function was restored
Six months after start of treatment.

Dependent Variables

Weight: To nearest 0.01kg
Height: To nearest 1mm
Hand-grip strength: To nearest 10g
Triceps skinfold: To nearest 0.2 mm
Plasma concentrations of vitamin A
Plasma concentrations of vitamin D
plasma concentrations of vitamin E
Plasma concentrations of albumin
Plasma concentrations of transferrin
Plasma concentrations of testosterone
Plasma concentrations of thyroid hormones
Health-related quality of life scores: Range from zero to 100 (measured at three timepoints).

Independent Variables

Treatment to six patients consisted of three courses with a four-week interval using a combination of vincristine (1.6mg) and doxorubicin (36mg per m²) for four days, and 40mg of dexamethasone daily for days one to four, days nine to 12 and days 17 to 20. This regimen regimen was replaced in September 2005 with a combination of cyclophosphamide (1g per m²) day one and 40mg of dexamethasone days one to four and days nine to 12; this CyDex regimen was given twice with a three-week interval to nine patients. Both treatments gave similar results on nutritional status so data are pooled.
Autologous stem cells were harvested 10 days after a dose of cyclophosphamide (2g per m²) and daily injections of granulocyte colony-stimulating factor (5mcg per kg). Patients received a high-dose of melphalan (200mg per m²) followed by autologous stem cell infusion two days later. Patients received antimicrobial treatment (200mg acyclovir daily and trimethoprim 80mg plus sulfamethoxazole 400mg every weekend) for three months after therapy.

Description of Actual Data Sample:

Initial N: 18
Attrition (final N): 15 (eight men and seven women)
Age: Ranging from 44 to 63 years old
Location: At a hospital in Oslo, Norway.

Summary of Results:

Key Findings

BMI remained fairly constant throughout the observation period except for a small but significant reduction when bone marrow functions was restored, corresponding to, on average, three weeks after stem cell function (P<0.05)
Hand-grip strength declined significantly and reached a nadir shortly before stem cell infusion, and stayed low until after recovery of bone marrow function (P<0.05)
TSF decreased significantly during treatment and with nadir when bone marrow function had been restored (P<0.05)
Vitamin A remained fairly unaltered during the observation period (P>0.05)
Vitamin D and vitamin E dropped significantly during treatment and remained low until after bone marrow recovery before their plasma concentrations returned to baseline levels at the end of the observation period (P<0.05)
No significant changes in the concentrations of the water-soluble vitamins B6, B12 or C
Thyroxin and thyroid-stimulating hormone both fell significantly during the observation period and reached a nadir at the time when bone marrow function was restored (P<0.05)
Testosterone-index, gonadotrophines luteinizing hormone nor follicle-stimulating hormone changed significantly during the observation period
Plasma albumin concentrations dropped significantly and reached a nadir at the time of high-dose melphalan (P<0.05)
Median plasma transferrin concentrations did not change appreciably during the observation period (P>0.05)
Health-related quality of life (HRQoL) scores at diagnosis, prior to high-dose melphalan and at the end of the observation period were measured. Global HRQoL remained rather constant throughout the observation period, all four symptoms scores increased significantly during therapy indicating worsening of symptoms before returning to pre-therapy levels at the end of the observation period (P>0.05).

Author Conclusion:

The author concludes that they demonstrated that multiple myeloma patients undergoing intensive treatment with high-dose melphalan supported by autologous stem cells, experience decline in nutritional status, measured as anthropometrical changes as well as reductions in biomarkers of nutrition. Whereas global health-related quality of life (HRQoL) was apparently unaffected, HRQoL-symptoms associated with nutritional impairment worsened during treatment.
Nutritional status in multiple myeloma patients deteriorated during intensive treatment, but improved after end of therapy. Whether multiple myeloma should be offered special nutritional support during treatment periods, remains to be studied.
Limitations: Limited sample size, the extent of mucositis was not evaluated and lacked direct measures of body composition.

Funding Source:

University/Hospital:

hospital in Oslo, Norway

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)	N/A
	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)	N/A

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?	???
	2.4.	Were the subjects/patients a representative sample of the relevant population?	???
3.	Were study groups comparable?		No
	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.)	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?	???
	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.)	???
	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%.)	???
	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?		No
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	No
	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?	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?	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)?	Yes
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	???
	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