To compare the efficacy (measured via incidence of febrile neutropenia [FN]) of levofloxacin versus oral third-generation cephalosporins (OTGCs) given as antibacterial prophylaxis during chemotherapy-induced neutropenia in high-risk patients with hematological malignancies. The goal was to demonstrate non-inferiority of OTGCs as an alternate therapy if fluoroquinolones were contraindicated. Secondary outcomes measured the incidence of bacterial infection between prophylactic drugs and compared the specific microorganisms identified in positive cultures.

Following induction chemotherapy for acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS), high-risk patients were prescribed levofloxacin 500 mg daily as antibiotic prophylaxis if appropriate. Similar patients who could not take levofloxacin because of intolerance, allergy, drug interaction, or previous adverse drug reactions were prescribed OTGCs (either cefdinir 300 mg twice daily or cefpodoxime 200 mg twice daily). The duration of antibiotic therapy was not specified. Chart reviews began with the start of antibiotic prophylaxis and continued until the earliest of 30 days following the last dose of antibiotic prophylaxis, the beginning of consolidation chemotherapy administration, or death. The two groups were compared for incidence of FN and for the secondary outcomes.

• N: 120   
• AGE: Median = 58.6 years (range = 19-80)
• MALES: 65%  
• FEMALES: 35%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: AML and MDS
• OTHER KEY SAMPLE CHARACTERISTICS: N/A

• SITE: Single site   
• SETTING TYPE: Inpatient    
• LOCATION: Mayo Clinic, Rochester, MN

PHASE OF CARE: Active anti-tumor treatment

Retrospective chart review, matching patients by OTGCs versus levofloxacin in a 1:2 ratio. Matching factors were age (plus or minus 5 years) and the Charlson comorbidity index (plus or minus 3).

Using retrospective chart review, researchers compared the incidence of FN, time to onset of FN, duration of neutropenia, site of infection, morphology of recovered organisms, and resistance to prophylactic agent.

The incidence of FN within 30 days of initiation of antibiotic prophylaxis was 83.4% (95% CI [65.8, 91.9]) in the OTGC group and 92.5% (95% CI [83.8, 96.5]) in the levofloxacin group, and was similar between the two groups (HR = 0.9, 95% CI [0.54, 1.52], p = 0.7). The median duration of neutropenia was also similar between the two groups, with 46 days (IQR = 26-67 days) for OTGCs and 39 days (IQR = 27-49 days) for levofloxacin. Similarly, the duration of prophylaxis prior to the onset of FN was comparable between the two groups (8 days for OTGCs, IQR = 6-12 days; and 8.5 days for levofloxacin, IQR = 5-13.5 days). Patients receiving OTGCs were significantly more likely to require ICU admission than those receiving levofloxacin (p = 0.04). The two groups had no significant differences in site of infection (p = 0.91) and morphology of recovered microorganism (p = 0.74). The OTGC group experienced significantly more cultures positive for Enterobacter (p = 0.043) than the levofloxacin group.

Although antibiotic prophylaxis with levofloxacin demonstrated advantages over OTGCs in the areas of avoidance of ICU admission and avoidance of cultures positive for the Enterobacter microorganism, OTGCs offer an acceptable alternative for those patients in whom fluoroquinolones are contraindicated.

• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Other limitations/explanation: Data collected were from only the first episode of FN following antibiotic prophylaxis.

The positive culture site was an implanted central venous catheter in the majority of patients (61.5%). This reinforces the need for nurses to maintain meticulous hand hygiene and infection control practices when working with central venous catheters.

STUDY PURPOSE: Analyzing interventions for management of chemotherapy-induced febrile neutropenia in adult patients with cancer.

TYPE OF STUDY: Systematic review

DATABASES USED: LILACS (Latin American and Caribbean Literature in Health Sciences), SciELO (Scientific Electronic Library Online), BVS (Virtual Library of Health), PubMed, CINAHL (The Cumulative Index to Nursing and Allied Health Literature), and Web of Science

YEARS INCLUDED: 2010-2015

INCLUSION CRITERIA: Primary articles published in English, Portugese, or Spanish, articles with methodology demonstrating interventions related to the management of chemotherapy-induced febrile neutropenia in adult patients, published between 2010-2015, full-text article availability in the selected databases

TOTAL REFERENCES RETRIEVED: 2,892 articles

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Duplicate articles were first removed from the original 2,892 articles retrieved, followed by elimination of articles that did not cover the research topic, and then finally articles that did not meet the inclusion criteria were removed from the original sample.

• FINAL NUMBER STUDIES INCLUDED: 12 
• TOTAL PATIENTS INCLUDED IN REVIEW: Information not included in the article
• SAMPLE RANGE ACROSS STUDIES: Adult patients treated for both hematologic and oncologic malignancies with chemotherapy who developed febrile neutropenia during some course of treatment, use of growth factors in this population in some studies as well 
• KEY SAMPLE CHARACTERISTICS: Adult patients with cancer being treated with chemotherapy, development of febrile neutropenia, treatment with various pharmacologic treatment

PHASE OF CARE: Active anti-tumor treatment

Prophylactic use of colony stimulating factors in patients was effective in avoiding reduction of chemotherapy doses and cycle delays. One of the studies cited use of piperacillin/tazobactam as effective treatment for febrile neutropenia while another one compared ciprofloxacin and cefepime, noting cefepime to be more effective. Neither study reviewed by authors presented a strong case for one antibiotic treatment over another. There were some studies included citing use of biomarkers to classify febrile neutropenia risk in patients and treat prophylactically for those at high risk in the outpatient setting.

Based on the review of these 12 studies, it is evident that the prophylactic use of growth stimulating factors in patients with cancer limits episodes of febrile neutropenia, particularly in diseases such as breast cancer and lymphoma where febrile neutropenia is well documented. There was not a general consensus that could be made for a specific antimicrobial treatment for these patients as many studies cited different medications that deemed effective for patients. Authors note lack of interdisciplinary literature regarding febrile neutropenia guidelines.

• Limited search
• Limited number of studies included

Authors cite the need to have nurses, as well as pharmacists and other members of the interdisciplinary team, involved in development of guidelines and protocols as all members of the team treat these patients and need to be knowledgeable about febrile neutropenia.

To describe how safe and effective fluoroquinolone prophylaxis is for patients with a deficiency of enzyme G6PD who are undergoing treatment for hematologic malignancies

Study participants received prophylaxis with either levofloxacin (500 mg/qd) or ciprofloxacin (500 mg/bid) beginning with initial chemotherapy administration until absolute neutrophil count recovers to greater than 1,000. Participants also received prophylactic antifungal therapy (fluconazole, posaconazole, or voriconazole).

• N = 242   
• AGE: 18-75
• MALES: 57%  
• FEMALES: 43%
• CURRENT TREATMENT: Chemotherapy, other (HSCT conditioning regimens)
• KEY DISEASE CHARACTERISTICS: Acute leukemia, Hodgkin and non-Hodgkin lymphoma, multiple myeloma
• OTHER KEY SAMPLE CHARACTERISTICS: Hematopoietic stem cell transplantation: autologous (n = 106, 44%); allogeneic (n = 49, 20%)

• SITE: Not stated/unknown   
• SETTING TYPE: Not specified    
• LOCATION: Italy

PHASE OF CARE: Active anti-tumor treatment

Retrospective cohort study

Patients were identified as having G6PD deficiency based on enzyme activity testing using the G6PD/6PGD Automatic Analyzer (KUADRO), Nurex SRL. Study definitions of “infection” included:

• “Microbiological documented infection” – When infectious agent was identified by culture or biopsy
• “Clinical documented infection” – When infection was identified, but infectious agent was not identified. 

Febrile neutropenia was assigned only when it occurred during the patient’s first episode of neutropenia (absolute neutrophil count of 1,000 mm³ or less). However, authors did not include a definition of acute hemolytic anemia.

Overall, patients with G6PD deficiency had fewer cases of febrile neutropenia (p = 0.01; hazard ratio 0.46; 95% confidence interval [0.25, 0.8]). The subset of patients treated for AML with G6PD deficiency had a higher risk of invasive fungal diseases (p < 0.0001; HR 11.4; 95% CI [3.5, 37.05]) and sepsis due to Candida (p = 0.008; HR 37; 95% CI [2.01, 680.9]). However, incidence of bacterial infection between groups was not statistically significant. Incidence of febrile neutropenia was slightly less (p = 0.01) among study participants with G6PD deficiency. Evaluation of 3,904 red blood cell units administered to study participants identified zero cases of acute hemolytic anemia for all patients regardless of G6PD status.

Fluoroquinolone prophylaxis did not appear to increase risk of acute hemolytic anemia-based on G6PD enzyme status. Patients with G6PD deficiency may be at higher risk of fungal infection, but lower risk of febrile neutropenia during intensive chemotherapy to treat hematologic malignancies.

• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Selective outcomes reporting
• Other limitations/explanation: Molecular testing results for G6PD were not available. In addition, unclear that analysis of a single potential complication (incidence of acute hemolytic anemia) is sufficient to assess safety. Unclear that single institution, retrospective study is sufficient to assess efficacy.

There is no indication that fluoroquinolone prophylaxis is unsafe or ineffective at reducing the risk of febrile neutropenia, regardless of G6PD enzyme status. If G6PD testing results are available, nurses may need to consider their patients with G6PD deficiency at higher risk for invasive fungal infections while on fluoroquinolone prophylaxis.

STUDY PURPOSE: To assess whether the recommendation by the European Conference on Infections in Leukemia to use fluoroquinolone prophylaxis for patients with high-risk neutropenia has resulted in a reduction in infection and mortality. A secondary objective was to assess the effect of fluoroquinolone prophylaxis on antibiotic resistance.

TYPE OF STUDY: Meta analysis and systematic review

DATABASES USED: PubMed

YEARS INCLUDED: 2006-2014

INCLUSION CRITERIA: Article assessed fluoroquinolone prophylaxis among patients with high-risk neutropenia undergoing treatment for blood cancer or patients post-hematopoietic cell transplantation (HCT)

EXCLUSION CRITERIA: (a) No assessment of antibiotic prophylaxis; (b) unable to discern whether the research question was relevant; (c) antibiotic prophylaxis included a non-fluoroquinolone

TOTAL REFERENCES RETRIEVED: N = 68

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Multiple statistical methods were applied to evaluate the studies included in the review. In addition, community prevalence of fluoroquinolone resistance was evaluated based on study data included in the review and previous studies.

FINAL NUMBER STUDIES INCLUDED: 14 

TOTAL PATIENTS INCLUDED IN REVIEW: 5,930

SAMPLE RANGE ACROSS STUDIES: 45–1,981

KEY SAMPLE CHARACTERISTICS: Study populations included patients with acute leukemias, hematologic malignancies, or post-autologous or allogeneic HCT. Studies included years of observation from 1998–2012.

PHASE OF CARE: Active anti-tumor treatment

Of the 14 studies analyzed, 12 were observational and two were randomized controlled trials. Overall, the odds ratio with fluoroquinolone prophylaxis were:

• Overall mortality = 1.01; 95% confidence interval [0.73, 1.41]
• Bloodstream infections = 0.57; 95% CI [0.43, 0.74]
• Febrile neutropenia = 0.32; 95% CI [0.2, 0.5]

However, in the analysis of three meta-analyses, published since 2006, Gafter-Gvili et al. (2012) found a statistically significant decrease in overall mortality (2.8% versus 5.3%, p = 0.00012). The rate of infection caused by fluoroquinolone resistant bacteria was 4% for patients who received prophylaxis and for patients who did not receive prophylaxis. There is insufficient data to determine the role of fluoroquinolone prophylaxis on the appearance of new, resistant bacteria.

Fluoroquinolone prophylaxis did not reduce overall mortality for patients with high risk neutropenia. However, there is some evidence that it may reduce the rate of bloodstream infections and febrile neutropenia. Clinically, the impact of prophylaxis may be low since many patients still develop febrile neutropenia and other risks, including Clostridium difficile infection and fluoroquinolone toxicity, were not analyzed. However, since most international guidelines with the exception of Australia, recommend fluoroquinolone prophylaxis, and there is insufficient conclusive evidence to recommend otherwise, the overall recommendation is to follow institutional policies but seriously consider the risks and benefits of prophylaxis for each patient.

Most of the 14 studies included in the analysis (12) were observational.

In the absence of contraindication or risk of complication with prophylaxis, there is insufficient evidence to routinely omit fluoroquinolone prophylaxis. Consider the risks and benefits of fluoroquinolone prophylaxis for each patient individually. Recognize the clinical benefit for an individual may be minimal. Consider review and update to institutional policies accordingly.

To evaluate the safety and efficacy of oral levofloxacin in preventing febrile neutropenia (FN) in patients who have received consolidation chemotherapy for acute myeloid leukemia (AML)

Following consolidation chemotherapy with: (1) cytarabine 3 g/m² IV q 12 hours on days 1, 3, and 5; (2) fludarabine 30 mg/m² IV on days 1-5, and cytarabine 2 g/m² IV on days 1-5, with or without filgrastim 300-480 mcg SQ daily beginning on day 6 until neutrophil recovery; or (3) mitoxantrone 6 mg/m² IV on days 1-3 and cytarabine 2 g/m² IV q 12 hours on days 1-3 for cycle 1 and 1 g/m² for cycle 2; hematologists chose whether to prescribe levofloxacin or not. This retrospective chart review compared the levofloxacin group to the no levofloxacin group. The primary efficacy outcome compared rehospitalization rates between those who received levofloxacin and those who did not. Secondary outcomes assessed duration of antibiotic treatment needed for FN and compared rates of Clostridium difficile-associated diarrhea (CDAD) between the two groups.

• N = 100   
• AGE: 18 years or older, 31% were aged 60 years or older; mean = 51.2 years
• MALES: 50%  
• FEMALES: 50%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: AML

• SITE: Single site   
• SETTING TYPE: Not specified    
• LOCATION: London, Ontario, Canada

PHASE OF CARE: Transition phase after active treatment

Retrospective chart review of AML patients, 50 of whom had received levofloxacin following consolidation chemotherapy and 50 of whom had not.

To evaluate the primary outcome, researchers tracked the rate of hospital readmission because of FN. Secondary outcomes considered the total number of days of antibiotic therapy required to recover from FN and counted the number of days between hospital discharge after consolidation chemotherapy and readmission for FN. Safety outcomes compared the rate of CDAD between the levofloxacin and no levofloxacin groups within 30 days following hospital discharge following consolidation chemotherapy, the relative rates of positive blood cultures in FN patients, the relative rates of resistance to levofloxacin from positive bacterial cultures, and the impact of levofloxacin on the spectrum of bacteria identified from positive cultures.

Following the first cycle of consolidation chemotherapy, 42% of patients who received levofloxacin were readmitted for FN. The no levofloxacin group had a readmission rate of 72% (p = 0.002). Results following all cycles of consolidation chemotherapy were less dramatic but still demonstrated the benefit of levofloxacin therapy (51.4% readmission for FN in the levofloxacin group, compared to 67% in the no levofloxacin” group (p = 0.023). There were no significant differences between the two groups in terms of total number of antibiotic treatment days (median 11 versus 10, p = 0.639), mean day of readmission after discharge from receiving consolidation chemotherapy (11.58 versus 10.37, p = 0.205), and rate of positive bacterial culture in readmitted FN patients (28.9 versus 42.9, p = 0.148).

This study supports the previously-established Infectious Diseases Society of America and National Comprehensive Cancer Network guidelines for antibiotic prophylaxis for cancer patients at high risk of developing FN. Levofloxacin use had no significant impact on any of the secondary outcome measures.

• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Key sample group differences that could influence results
• Other limitations/explanation: The patients in this study received one of three different regimens of consolidation chemotherapy, but the study did not divide these patients into different arms. Furthermore, the dose and duration of levofloxacin therapy were not standardized.

This retrospective chart review did not separate the various consolidation chemotherapy regimens into separate arms. The authors searched until they found the intended sample size of patients who had received levofloxacin and those who had not. Of note, the levofloxacin dose and duration of fluoroquinolone therapy was not standardized.

STUDY PURPOSE: To compare the effectiveness and safety of antipseudomonal b-lactam empiric monotherapy for febrile neutropenia by network meta-analysis

TYPE OF STUDY: Meta analysis and systematic review

DATABASES USED: PubMed, Cochrane CENTRAL, EMBASE, and Web of Science Core Collection

YEARS INCLUDED: No year limitation

INCLUSION CRITERIA: Definition of febrile neutropenia was ANC less 500 mcl or less than 1,000 mcl and temperature greater than 38 C for more than one hour or temperature greater than 38.3 C. Patients in both arms had to be treated with IV antipseudomonal beta-lactam antibiotic for initial empiric therapy of febrile neutropenia. GCSF use was allowed.

EXCLUSION CRITERIA: Granulocyte transfusion was excluded. Antibiotics not evaluated in a RCT in the past 10 years (since 2006) were excluded.

TOTAL REFERENCES RETRIEVED: 1,275

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Evaluated quality of each study using 6 domains of the Cochrane risk of bias tool

FINAL NUMBER STUDIES INCLUDED: 50 studies

TOTAL PATIENTS INCLUDED IN REVIEW: 10,872 patients

KEY SAMPLE CHARACTERISTICS: Adult and pediatric febrile neutropenia patients undergoing chemotherapy for either solid tumors or hematologic malignancies.

PHASE OF CARE: Active anti-tumor treatment     

APPLICATIONS: Elder care

Treatment success without antibiotic modification was most likely with Cefoperazone/sulbactam followed by imipenem/cilastatin, piperacillin/tazobactam, meropenem, cefepime, cefozopran, ceftazidime and panipenem/betamipron. The risk for all-cause death was lowest in all-cause death were lowest in the imipenem/cilastatin arm and highest in the cefepime arm.

Imipenem/cilastatin followed by piperacillin/tazobactam and meropenem had the best performance in the treatment success without modification and all-cause death.

• Low sample sizes
• Inconsistent definitions of neutropenic fever and treatment success; only included studies of adult patients

Antipseudomonal antibiotics are effective for empiric treatment of febrile neutropenia and imipenem/cilastatin, piperacillin/tazobactam, and meropenem had the best performance in the treatment success without modification and all-cause death. This may be due to increasing incidence of extended spectrum beta lactamase-producing bacteria that are resistant to cefepime. However, cefepime is still recommended by major guidelines for initial use and remains a reasonable choice, particularly given the concern of antibiotic resistance using carbapenems as initial empiric therapy for febrile neutropenia.

The purpose of this study was to evaluate the effect of recombinant factor VIIa (rFVIIa) upon severe bleeding in patients with platelet transfusion refractoriness.

Patients in the intervention group received 60 ug/kg of recombinant factor VIIa intravenously, with or without conventional treatment. Those in the control group received only conventional treatment. Dosing of rFVIIa was dependent on clinical characteristics and response to treatment. Conventional treatments included transfusion of platelets, plasma, or cryoprecipitate, or medications such as hemocoagulase atrox or carbazochrome sodium sulfonate.

• N = 64   
• AGE: Mean age was 35 years.
• MALES: Not available  
• FEMALES: Not available 
• CURRENT TREATMENT: Other
• KEY DISEASE CHARACTERISTICS: Hematologic malignancies

• SITE: Single site   
• SETTING TYPE: Inpatient    
• LOCATION: University Hospital in Soochow, China

PHASE OF CARE: Active antitumor treatment

This was a controlled prospective study. Randomization was not stated.

Bleeding severity was graded according to criteria established by Nevo et al. (1999): 0 (no bleeding) to 4 (massive bleeding leading to hemodynamic compromise or bleeding into a vital organ). Major bleeding was graded according to criteria from the International Society on Thrombosis and Hemostasis.

Response rates to hemostatic treatment were significantly higher in the intervention group receiving rFVIIa at 24 hours (p = 0.014) and 48 hours (p = 0.020) when compared to the control group. Patients achieving a complete remission were also significantly higher in the intervention group at 24 hours (p = 0.031), 48 hours (p = 0.039), and 72 hours (p = 0.021). Bleeding score and time to control bleeding were significantly reduced in the intervention group (p = 0.029 and p = 0.034).

Administration of rfVIIa was significantly more likely to lead to control of bleeding and decreased time to control bleeding in patients with hematologic malignancies with severe thrombocytopenia, who were refractory to platelet transfusions. In addition, patients receiving rFVIIa were significantly more likely to have a complete remission than those who did not receive rFVIIa.

• Small sample (< 100)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Other limitations/explanation: There were no standard number of doses received or threshold when given, except for clinical assessment (median number was 3, range was 1-15).

The administration of rFVIIa may be considered an effective adjunct to conventional therapy to reduce bleeding in patients with hematologic malignancies who are refractory to platelet transfusions, along with use of HLA-matched or cross-matched platelets, to improve outcomes.

The purpose of this study was to evaluate the effect of a protein pump inhibitor on tumor bleeding prevention in patients with advanced gastric cancer. The primary endpoint was tumor bleeding; secondary endpoints were the number of transfusions received and overall survival.

Patients with inoperable gastric cancer were randomized into one of two groups, with stratification based on hemoglobin level. The study group received lansoprazole 30 mg PO every day. The control group received placebo. Bleeding rates were assessed at 4 months and at a median follow up of 6.4 months. Bleeding was assessed by blood counts every three weeks.

• N = 127   
• AGE: Median is 56 years.
• MALES: 78.7%  
• FEMALES: 21.3%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Unresectable gastric cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Age ≥ 18 years, ECOG 0-2

• SITE: Multisite   
• SETTING TYPE: Outpatient    
• LOCATION: Korea

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Palliative care

Prospective, randomized, double-blind, placebo controlled trial

Bleeding events were defined as the presence of witnessed melena or hematemesis, decrease in hemoglobin by greater than 2 g/dL in one week, or > 3 g/dL in three weeks, with endoscopic evidence of bleeding. Endoscopic bleeds were graded per Forrest classification. Gray’s test and the Fine-Gray regression model were used to evaluate time to tumor bleeding events and the effect of lansoprazole upon bleeding.

There was no significant difference in tumor bleeding between the two groups.

Lansoprazole did not have a preventive effect on tumor bleeding in patients with inoperable gastric cancer, nor was there a difference in the number of transfusions required. The lansoprazole group did have a significantly reduced number of tumor bleeding events compared with placebo, until the four-month mark. At that point forward, the difference became statistically insignificant. This may be related to disease progression and increased tumor burden during palliative chemotherapy treatment.

• Unintended interventions or applicable interventions not described that would influence results
• Other limitations or explanation: The study was underpowered for the primary outcome. Patients were receiving first- or second-line chemotherapy during the study. The study planned to enroll 394 patients but ended because of a low recruitment rate. The study did not look at various dosing options of lansoprazole. Many patients were lost to follow up. Median follow-up duration was brief. The placebo group included more patients who received second-line chemotherapy.

The risk of tumor bleeding in patients with inoperable gastric cancer is not decreased with 30 mg of lansoprazole daily, nor did it decrease the requirement for transfusions.

PURPOSE: To provide evidence-based guidance on the use of platelet transfusion in patients with cancer.

TYPES OF PATIENTS ADDRESSED: Adults and children (> 4 months of age)

RESOURCE TYPE: Evidence-based guideline

PROCESS OF DEVELOPMENT: Expert panel conducted an SR from 2014-2016. The current guideline builds on previous ASCO guidelines first published in 2001. For new questions not addressed by previous guidelines, the search went back to 2000.

DATABASES USED: PubMed and Cochrane     
    

INCLUSION CRITERIA: Adults and children (> 4 months) with cancer, prophylactic or therapeutic platelet transfusion; outcomes were bleeding, alloimmunization, and platelet refractoriness. Publication types were CPG, SR, MA, RCT, and observational studies.
  

 EXCLUSION CRITERIA: Meeting abstracts not published in peer-reviewed journals, editorials, etc. Non-English publications

PHASE OF CARE: Multiple phases of care

APPLICATIONS: Pediatrics, elder care, palliative care

24 total publications were new to this guideline: 3 CPG, 8 SRs, and 13 observational studies.

The most significant change involved platelet transfusion in HSCT. Adult patients who undergo autologous stem cell transplantation at experienced centers may receive a transfusion at the first sign of bleeding. Prophylactic platelet transfusion at defined thresholds is still recommended for pediatric patients undergoing autologous SCT and for adults and pediatric patients undergoing allogeneic SCT.

Relatively few studies are available on prophylactic platelet transfusions in solid tumors, and information is lacking about the safety of invasive procedures in patients with thrombocytopenia.

This is an updated guideline for adult and pediatric patients who require platelet transfusions.

STUDY PURPOSE: The primary aim was to evaluate the safety of lysine analogs administered to patients with cancer, with respect to the development of thromboembolic events. The secondary outcome was the efficacy of lysine analogs administered to patients with cancer, with respect to transfusion risk and blood loss.

TYPE OF STUDY: Meta-analysis and systematic review

DATABASES USED: MEDLINE, Embase, Cochrane Library

YEARS INCLUDED: Inception to June 2016

INCLUSION CRITERIA: Randomized controlled trials comparing administration of a lysine analog to either placebo or active control, or standard of care in surgical and nonsurgical patients with cancer. 

EXCLUSION CRITERIA: No specific exclusion criteria

TOTAL REFERENCES RETRIEVED: N = 5,627 records were retrieved.

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Studies were selected for review based on PRISMA guidelines. A standardized data review extraction form was piloted by the two reviewers; the Cochrane Risk of Bias Tool was utilized to assess the risk of bias.

• FINAL NUMBER STUDIES INCLUDED: N = 11 
• TOTAL PATIENTS INCLUDED IN REVIEW: 1,177
• SAMPLE RANGE ACROSS STUDIES: 12-219
• KEY SAMPLE CHARACTERISTICS: surgical and nonsurgical patients with cancer were included; TXA was administered in nine trials, EACA in one, and both lysine analogs in one study.

PHASE OF CARE: Multiple phases of care     

APPLICATIONS: Elder care, palliative care

There was a significant reduction in blood loss noted in 9 of 11 studies in which a lysine analog was administered. Data from two studies were not included in the meta-analysis because of statistical heterogeneity between trials. In the seven studies reporting transfusion data, there was a significant decrease in the risk of receiving a blood transfusion in patients who had received a lysine analog.

The administration of a lysine analog was correlated with a significant reduction in blood loss and the risk of receiving a blood transfusion in patients with cancer.

• Limited number of studies included
• Mostly low-quality and/or high risk of bias studies   
• High heterogeneity   
• Low sample sizes
• Efficacy of lysine analogs administered to patients with cancer, with respect to transfusion risk and blood loss, was a secondary outcome. It is not clear from this review what search items were used: were only studies evaluated which included information regarding efficacy and VTE? If so, that would omit studies which only evaluated efficacy.

The administration of lysine analogs in patients with cancer has been shown to be efficacious in the reduction of blood loss and in reducing the risk of receiving a blood transfusion. Nurses, however, need to be aware of the potential inherent risks of VTE-associated administration of these agents. This has not been adequately studied, to date.