To analyze the current guidelines and recommendations for the prevention of infectious complications in adults and children undergoing hematopoietic stem cell transplantation (HSCT).

This resource is a guideline.  A mini-review of evidence-based recommendations was conducted on the prevention of infections after HSCT in children.  These recommendations were rated based on the strength of the recommendation and supporting evidence quality.  The evidence-based system (A-E, I-III) was used to establish the strength of the recommendations and the quality of the supporting evidence.

Databases searched were not stated.  The authors stated that they reviewed current guidelines, but the guidelines were not specifically identified.

Search keywords were prophylaxis, infection, hematopoietic SCT, strategy, and vaccination.

Studies were included in the review if they reported adults and children undergoing HSCT.  The exclusion criteria were not reported.

The study has clinical applicability for pediatrics.

In the hospital environment, cleaning all surfaces to prevent dust accumulation, separating patient wards from outside air, and housing patients in rooms with high-efficiency particulate absorption filters were category AII recommendations.  Having patients wear masks when going to unprotected areas and providing rooms with positive pressure were category BIII recommendations.  Hand washing to minimize hospital-acquired candidal and bacterial infections was rated AIII.  Antibacterial prophylaxis for all patients from conditioning through engraftment was strongly recommended (AI), with ciprofloxacin, levofloxacin, and amoxicillin-clavulanate.  Fungi prophylaxis was recommended with fluconasole, voriconazole, posaconazole, or (BII) itraconazole for all patients. Cytomegalovirus prophylaxis with ganciclovir was recommended (AI) for high-risk patients.  Herpes simplex virus prophylaxis for IgG-positive patients was recommended (AI) with valacyclovir. Varicella-zoster virus prophylaxis was recommended for IgG-positive patients.  Vaccinations were not supported by any AI recommendations.  Annual inactivated influenza viral vaccine and conjugated Streptococcus pneumonia vaccine for all patients undergoing HSCT both received a category AII recommendation.  Viral polio inactivated, hepatitis B, bacterial conjugated Haemophilus influenzae B, toxoid tetanus, toxoid diphtheria, and polysaccharide S. pneumonia vaccines all received category recommendations.  (See Table 1 for the evidence-based rating.)

Table 1 (as shown in the article)

“Category definition to determine strength of recommendation:

• (A)  Should always be offered
• (B)  Should generally be offered
• (C)  Optional
• (D)  Should generally not be offered
• (E)  Should never be offered

Category definitions to determine quality of supporting evidence

• (I)  Evidence from at least one properly randomized and controlled trial
• (II)  Evidence from at least one well-designed clinical trial without randomization, from cohort or case-controlled analytic studies (preferably from more than one center), or from multiple time series or dramatic results from uncontrolled experiments
• (III)  Evidence from opinions of respected authorities based on clinical experience, descriptive studies or reports of expert committees.”

Table 2 provides antimicrobial prophylaxis type, indication, first and second recommendation using A-E, I–III ratings, and when to begin and end therapy.  Table 3 lists recommendations for vaccinations after HSCT by delineating viral and bacteria vaccines, type of vaccine, time to begin, number of doses, indications, and recommendations using A-E, I–III categories.

Conflict of Interest: Jan Styczynski and Lidia Gil have received speakers’ fees from Medagro and MSD.

Cotrimoxazole or quinolones antibacterial prophylaxis has demonstrated efficacy for patients with cancer who are neutropenic and after autologous HSCT (category AI), but well-designed clinical trials specifically for patients undergoing allogeneic HSCT are not available.  Studies with mostly adults receiving fluoroquinolones for HSCT were analyzed to deem the safety for children.  Using fluoroquinolones safely in children is based on one double-blind, placebo-controlled, randomized pediatric clinical trial using amoxicillin clavulanate, and patients undergoing HSCT were not included. High- and intermediate-risk patients should be offered antifungal prophylaxis.  Fluconazole, micafungin (both category AI), and itraconazole (category BI) are recommended during pre-engraftment for antifungal prophylaxis.  In adults with severe acute or extensive chronic graft-versus-host disease, oral posaconazole has been shown to be effective in reducing invasive mycoses.  No data on dose and schedule were reported for pediatric dosing.  Oral valganciclovir has been shown to be effective when compared to intravenous ganciclovir, but no pediatric data were available, and the drug was not available in liquid suspension, which is often desirable for children.  Vaccination against influenza and S. pneumoniae for HSCT was strongly recommended (category AII for both).  Live tuberculosis should never be offered (EII).  Other vaccinations have the potential for decreasing post-HSCT risks for vaccine-preventable infections.  High quality supporting evidence used in this guideline was based on as little as one randomized, controlled trial, with no discussion of sample size, risk of bias, etc., making this a relatively low threshold for highly rated evidence.

To determine whether the addition of oat bran to the diets of older adult residents of a long-term care facility would lead to a reduction in laxative use.

The control group (15 patients assigned) received usual diet.

The intervention group had oat fiber containing 8.3 g of nondigestible fermentable fiber and 9.7 g of nondigestible nonfermentable fiber per 100 g incorporated into their diet for 12 weeks.

• The study reported on a sample of 30 older adult patients.
• Patient age ranged from 57 to 98 years. Mean age was 86 years (SD = 9) in the intervention group and 84.6 years (SD = 11.4) in the control group.
• Gender information was not provided.
• Patients were excluded if they were receiving parenteral or enteral nutrition or any medication that would alter transit time through the gut.

Single ward of a long-term care facility in Vienna, Austria

The study has clinical applicability to older adult care.

This was a controlled, parallel, blind intervention trial.

• Nursing staff began recording laxative use after 10 days.
• Body weight was recorded on days 1, 42, and 84.
• Kilojoule (calorie) and fluid intake were recorded daily.
• Observations concerning patients' eating habits were used to adapt recipes to ensure compliance.

• The intervention group increased fiber intake by 5.1 g over the 12-week study period.
• The intervention group had a 59% reduction in laxative use (p < 0.001), with a constant body weight (p = 0.455). 
• The control group had a decrease in fiber intake by 1.8 g. Mean energy intake was 5,203 kilojoules (SD = 1,285) per day, and mean fluid intake was 1.794 ml (SD = 276 ml) per day.
• The control group increased laxative use by 8% (p = 0.218), and their body weight decreased significantly (p < 0.005).

Fiber supplementation with oat bran may be an alternative to laxatives for treating constipation in an older adult population.

• The study used a small convenience sample that did not include patients with cancer.
• Whether simple or double blinding was used is unclear.
• Exercise may have decreased constipation, but patients' activity level was not noted.

Increasing fiber supplementation with oat bran may be an alternative to laxative use for treating constipation in older adults. Additional study is warranted in a larger population that includes patients with cancer.

To evaluate the effect of dance on relieving fatigue in patients with cancer undergoing active cancer treatment

This study consisted of two groups, one with supportive consultation, fatigue counseling, nutrition counseling, psychooncology, and 10 60-minute dance classes for five weeks, and the other with everything except the dance class.

• N = 40  
• AGE RANGE = 26–71 years
• MALES: 3 (7%), FEMALES: 37 (93%)
• KEY DISEASE CHARACTERISTICS: Breast, ovarian, gastrointestinal, and other cancers; patients receiving chemotherapy, radiation, and hormonal therapy in the adjuvant, neoadjuvant, and palliative care settings

• SITE: Single-site    
• SETTING TYPE: Outpatient    
• LOCATION: Berlin

• PHASE OF CARE: Active antitumor treatment

Nonrandomized intervention

• Fatigue Visual Analog Scale (VAS)
• European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30)
• 6-Minute Walk Test (6MWT)
• Functional Assessment of Chronic Illness Therapy (FACIT)
• Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F)

Fatigue was measured at baseline and at the end of the study for both groups. There was significant reduction in fatigue in the dance group while fatigue essentially was unchanged in the control group. The study also demonstrated improved scores on the social and emotional functioning scales and in physical performance in the dance group.

Dance could be an appropriate, multidimensional approach for the treatment of cancer-related fatigue.

• Small sample (< 100)
• Risk of bias (no random assignment)
• Key sample group differences that could influence results

To encourage exercise or movement, this study offers a less monotonous approach compared to conventional fitness programs addressing cancer-related fatigue. Replication and a randomized study is needed to establish effectiveness.

To test hypotheses regarding the effect of massage on anxiety, pain, nausea, sleep, and quality of life (QOL).

Patients were referred by their physicians and were provided a physician order for massage. Patients completed self-administered instruments prior to massage therapy and one week after therapy. Massage treatments lasted 30 minutes and were provided during treatment with chemotherapy and/or radiation therapy (RT) once per week for three weeks.

• The sample was comprised of 51 women with breast cancer.
• Mean age was 53 years.
• All patients were diagnosed with breast cancer; 27% had recurrence.
• The majority (78%) of patients were receiving only chemotherapy, and 61% were either also receiving concurrent RT or had RT planned in the future.
• The sample was 84% Caucasian, with 45% currently working full-time and 88% having at least some college education.

• Single site
• Outpatient
• Kansas

Patients were undergoing the active treatment phase of care.

The study used a pre-/posttest design.

• State-Trait Anxiety Inventory (STAI)
• Visual analog scale (VAS) for pain
• Symptom Distress Scale (SDS)
• Verran and Snyder-Halpern Sleep Scale (VSH)
• Functional Assessment of Cancer Therapy–Breast (FACT-B)

STAI scores were lower after massage therapy (p = 0.03). Sleep scale items that showed improvement with massage were soundness of sleep (p = 0.05), time from settling down to sleeping (p = 0.02), and overall sleep satisfaction (p = 0.01). FACT-B scores also showed improvement in several areas after massage therapy (p < 0.05). Effect sizes in these areas were moderate (≥0.3).

Provision of massage therapy during treatment for breast cancer may reduce anxiety and improve sleep and aspects of QOL.

• The study had a small sample, with less than 100 patients.
• The study lacked a control or comparison group.
• The study lacked blinding, and the massage therapist obtained all self-reported data.
• The study had a short duration of intervention and follow-up.
• The sample was highly educated and overwhelmingly Caucasian, with 52% of patients earning more than $50,000. The findings may not be generalizable to other socioeconomic and ethnic groups.

Massage therapy may assist women undergoing breast cancer treatment to better tolerate the impact of treatment, reduce anxiety, and improve sleep during active treatment.

STUDY PURPOSE: To assess the effects of conservative (nonsurgical and nonpharmacologic) interventions on lymphedema after breast cancer treatment

TYPE OF STUDY: Systematic review

DATABASES USED: Cochrane Breast Cancer Group’s (CBCG) Specialized Register, CENTRAL, MEDLINE, EMBASE, CINAHL, PEDro, PsycINFO, and the World Health Organization International Clinical Trials Registry Platform in May 2013 (reference lists of included trials and other systematic reviews were searched)

• FINAL NUMBER STUDIES INCLUDED = 10
• TOTAL PATIENTS INCLUDED IN REVIEW = 1,122
• SAMPLE RANGE ACROSS STUDIES: 48–205 patients
• KEY SAMPLE CHARACTERISTICS: All had breast cancer

PHASE OF CARE: Late effects and survivorship

The evidence from this review was insufficient to draw firm conclusions.

All included studies were deemed to be of low or very low quality.

The quality of the evidence regarding interventions for reducing the risk of lymphedema remains low. More research is needed.

The study examined the neuroprotective effect of glutamine.

Seventeen patients received 10 g of glutamine administered three times daily for a total of four days beginning 24 hours after completion of paclitaxel. The remaining 29 patients made up the control group. Neurologic assessments and electrodiagnostic (nerve conduction) studies were carried out at baseline and at least two weeks (median 32 days) after treatment by a neurologist. Neurologic signs and symptoms also were assessed.

The study sample consisted of 46 patients who received high-dose paclitaxel prior to stem cell transplantation.

The study had a retrospective, non-randomized design.

Patients who received glutamine developed less weakness, less loss of vibratory sensation, and less toe numbness compared to those in the control group. A trend toward reducing symptoms of finger numbness was noted. In the comparison group, three patients developed foot drop and four patients developed tibialis weakness.

The mechanism of neuroprotection conferred by glutamine is unclear; some evidence suggests a correlation between treatment-induced reduction in nerve growth and severity of neurotoxicity.

The limitations of this study include it not being randomized or blinded as well as the fact that no placebo control group was used.

Results of this study should be interpreted with caution because of the small sample size and the non-randomized, retrospective design.

This study outlines the common antineoplastic agents known to cause neuropathy and provides information on incidence, onset dosages, the signs and symptoms, and general course and patterns of resolution. Agents identified include platinum compounds, vinca alkaloids, taxanes, bortezomib, ixabepilone, thalidomide, and lenalidomide. In addition to outlining the mechanisms of neuropathy development in cancer, the study discusses neurophysiologic and objective testing, noting that findings on electromyographic (EMG) and nerve conduction studies (NCS) can lag behind clinical symptoms. The study also identifies commonly used physician-based grading systems, including the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) and Eastern Cooperative Oncology Group (ECOG) systems, and notes that these two grading systems lack inter-rater reliability. Patient-based instruments for assessment include the Functional Assessment of Cancer Treatment (FACT) and the Patient Neurotoxicity Questionnaire (PNQ). The authors note that the routine assessment of pain secondary to neuropathy, using instruments such as the Brief Pain Inventory (BPI), is useful.

Routine assessment should be conducted and continued throughout therapy. Key points in assessment that should be included are:

• History, related comorbid conditions, alcohol use, symptoms, pain assessment, time course, and treatment delays or discontinuation from CIPN
• Physical examination
• Patient interview questions regarding sensation of numbness or tingling, pain, bothersome sensations, weakness, difficulty walking, falls, and interference with activities of daily living
• Functional skills testing, such as straight-line walking, name writing, buttoning, pegboard tests, and timed pellet retrieval.

Proposed agents for prevention of CIPN identified include:

• Agents with positive findings: vitamin E, calcium, magnesium, glutamine, glutathione, N-acetylcysteine, oxcarbazepine, xaliproden
• Agents with negative findings: amifostine, nimodipine, Org2766, rhuLIF
• Agents being tested in trials: vitamins B12, B6, acetyl-L-carnititne, alpha lipoic acid

Agents used for pain management:

• Those with negative results in CIPN, including gabapentin, amitriptyline, notriptyline
• Other agents commonly used include duloxetine, 5% lidocaine patch, opioids, tramadol

Current literature is inconclusive on the benefits of neurostimulation in treating CIPN. The authors note that evidence is scarce on efficacy of complimentary and alternative medicine (CAM) therapies and the need for appropriately powered and controlled studies in this area. However, acupuncture was identified as a promising adjunct option. The article also provides safety tips and issues for management of functional deficits in PIN, including situations in which to avoid or discontinue physical training, footwear selection, orthosis, and safety aspects of the household environment. Finally, the article addresses how autonomic neuropathy from chemotherapy occurs, but has not been well documented or studied.

• Limitations include a significant lack of evidence regarding effective management and prevention in this area.
• The review did not describe a search strategy or process to determine the quality of evidence used.

The article provides a comprehensive review of current knowledge about CIPN and common approaches toward assessment, prevention, and management. The authors do not make specific recommendations for treatment, research to validate evaluation tools, and exploration of combinations and scheduling of pain medications. In addition, testing of the safety and effectiveness of therapeutic interventions and dietary supplements are needed.

To determine the effectiveness of integrating a depression management program into the care of patients with cancer and major depressive disorder (MDD).

Patients were randomized into the treatment group or the usual care group. The treatment group received up to 10 individual one-to-one 45-minute sessions over a three-month period; some occurred via telephone or in the patients' homes, as needed. The intervention consisted of education about depression and its treatment, problem-solving and coping strategies, and collaboration with each patient’s oncologist and primary care provider. Two repeat sessions were offered to persons whose Patient Health Questionnaire-9 (PHQ-9) scores were increasing. No further intervention occurred after six months, but a progress-monitoring interview was conducted at 12 months.

• The sample was comprised of 200 patients.
• Mean patient age in each group was 56.6 years.
• The usual care group included 71 women and 28 men, and the intervention group included 70 women and 31 men.
• Patients had breast, colorectal, gynecologic, genitourinary, hematologic, lung, and mixed cancers.
• Patients were eligible based on the presence of MDD antidepressant therapy (any dose or therapeutic dose). Symptoms (depression, anxiety, pain, fatigue, and physical functioning) were also identified.

• Home visit or telephone visit, if patients were unable to attend the single site
• Regional cancer treatment center in Scotland, United Kingdom

Patients were undergoing the active treatment and transitional phases of care.

The study was a randomized trial with a control (usual care) group.

• Hospital Anxiety and Depression Scale (HADS)
• Structured Clinical Interview for DSM-IV (SCID-IV), to determine if patients met the criteria for MDD
• PHQ-9, to assess the severity of depression
• Hopkins Symptom Checklist (SCL-20) depression scale, to measure changes in depression
• A 10-item subscale of the Symptom Checklist-90 (SCL-90) questionnaire, to measure anxiety
• European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)
• EuroQol EQ-5D questionnaire, to measure quality of life for economic analysis

Measurements revealed no statistically significant differences in the two groups at baseline, including differences in the use of antidepressant medication. However, at three and six months, more patients in the intervention group than in the control group were using a therapeutic level of antidepressants. Depression scores on the SCL-20 decreased between baseline and three months in both groups, but the scores decreased more in the intervention group. More patients in the intervention group had a depression score that decreased by at least 50% from baseline to the three-month follow-up (p = 0.0008). In addition, several patients in the intervention group no longer met the criteria for MDD at three months and had reduced anxiety and fatigue. The study showed no significant changes in pain or physical functioning at three or six months. In addition, at six and 12 months, the study showed a significant improvement in quality of life for patients in the intervention group.

Supplementation of usual care with a nurse-delivered intervention for the management of depression reduced the symptoms of depression, anxiety, and fatigue more than usual care alone. There were no significant improvements in pain or physical functioning. The authors noted the close relationship of anxiety and fatigue to depression as a possible rationale for the cluster of improvements.

• The study had risk of bias due to no attentional control.
• Patient bias may have affected the outcome assessments:  the Hawthorne effect may have applied because patients knew that management of depression was taught.

A cost-effective, patient-acceptable, nurse-delivered intervention can support the management of depression, anxiety, and fatigue in patients with cancer and MDD. At 12 months, the evidence showed a sustained effect of the three-month intervention.

Databases searched were MEDLINE, CINAHL, and Database of Abstracts of Reviews of Effects (DARE) through October 2003.  Proceedings of the annual meetings of the American Society of Clinical Oncology, American College of Sports Medicine, and Oncology Nursing Society were also searched.

Twenty experimental studies (nine randomized, clinical trials and 11 quasiexperimental studies) were included.  The outcome was fatigue. Treatment evaluated physical activity or group or individual exercise.

• Sample sizes ranged from nine to 11 participants.
• Participants were adults.
• Participants had breast cancer, mixed solid tumors, or hematologic malignancies; were receiving active treatment, including stem cell transplantation, radiation, or chemotherapy; were receiving or palliative care; or were long-term survivors.

There is strong evidence to support the effectiveness of home-based exercise programs performed by middle-aged women undergoing adjuvant chemotherapy or radiation therapy for nonmetastatic breast cancer and some evidence that exercise may be equally beneficial in other cancer populations, including individuals with solid tumors and hematologic malignancies and cancer survivors.  Based on current evidence, low-intensity exercise individualized to patient comfort is the only type of exercise that can be considered safe for patients in palliative care settings. Evidence supports the efficacy of aerobic laboratory-based interval training in individuals receiving peripheral blood stem cell transplantation.

All studies had some design limitations, including

• Small sample sizes
• No random assignment
• No control groups
• Failure to control for anemia levels, intensity of chemotherapy, and the timing of the fatigue measurement in relationship to chemotherapy treatments.

• FINAL NUMBER STUDIES INCLUDED = 18
• TOTAL PATIENTS INCLUDED IN REVIEW = 841 total patients in 10 randomized, controlled trials (RCTs) and 8 controlled clinical trials (CCTs)
• KEY SAMPLE CHARACTERISTICS: 11 studies in diabetic neuropathy, 1 study in chemotherapy-induced PNP, 6 studies with PNP of other derivations, 12 high quality studies (levels 1 and 2), 6 poor quality studies (level 4)

PHASE OF CARE: Multiple phases of care

Five studies assessed the influence of balance training on the side effects of PNP and showed a significant impact on balance control. Two studies also showed improved gait parameters. Improved motor, sensory, and metabolic symptoms was observed with tai chi. Combinations of endurance, balance, and strengthening exercises showed a positive effect on motor performance only if exercises were performed standing or walking. One RCT in chemotherapy-induced PNP showed that exercise (sensorimotor, endurance, and resistance training) can reduce quality of life, level of activity, and sensitivity. Only three studies in the cohort of those with PNP from various causes showed they were able to achieve improvements through the exercise regimen. The other three studies in this group showed no significant changes after intervention. None of the studies reported serious adverse effects, although one of the diabetic neuropathy studies reported one calf strain from treadmill walking.

Evidence for exercise interventions in those with PNP has improved, although study quality is diverse. Overall, the quality of studies included in this review was 2b with the best evidence in those with diabetes and PNP. Current data suggest that exercise is feasible, safe, and beneficial.  Exercise compliance was overall good, and only mild adverse events were reported. Specific treatment for nerve damage was not available, and the efficacy of pharmaceutical interventions is questionable.

Patient cohorts were very heterogeneous. Because of the heterogeneity, the results are not very generalizable. Eighteen studies were included (small sample).

More research is needed on exercise interventions, particularly in regard to the patients with cancer who have other symptoms to contend with as well. Nurses should educate patients about PNP and encourage enrollment in clinical trials if available.