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.

To test FOCUS, which is an evidence-based psychoeducational intervention, in terms of its feasibility, cost, and program satisfaction and assess its impact on patients' and caregivers' emotional distress and QOL as primary outcomes and benefits of illness, self-efficacy, and dyadic communication as secondary outcomes in two community service centers.

FOCUS is a psychoeducational intervention that is delivered to dyads of patients and their caregivers and addresses the following components: family involvement, optimistic attitude, coping effectiveness, uncertainty reduction, and symptom management. The components cover 104 activities relevant to the components in five sessions. The FOCUS program was administered by a trained social worker in one site and a family therapist in the second site. FOCUS was administered in a group format (3 to 4 dyads) and involved five weekly face-to-face sessions; each was two hours. 11 five-session programs were given over 12 months. The program implementation was guided by the Translating Research into Practice model; a one-day training program was held for the site directors and facilitators and they were given training manuals that were developed based on their role. Pre-packaged material to implement the five-week sessions were provided, weekly calls between program facilitators took place, and monthly meetings occurred between investigators.

• N = 36 dyads, 36 caregivers
• AGE: 55.9 years (SD = 15.1)
• MALES: 44.4%  
• FEMALES: 55.6%
• KEY DISEASE CHARACTERISTICS: Any cancer type, including advanced cancer, currently on treatment, or completed treatment in the past 18 months
• OTHER KEY SAMPLE CHARACTERISTICS: English-speaking only; married/partnered, largely Caucasian, with college degrees, and employed with moderate incomes, mostly caring for patients with stage II or IV cancer in current treatment

• SITE: Multi-site   
• SETTING TYPE: Other; local cancer support community. The CSC is a large network of community agencies in the United States that provide professional psychosocial care in a group format at no cost to patients with cancer and their caregivers.
• LOCATION: Cincinnati, Ohio and Santa Monica, California

PHASE OF CARE: Multiple phases of care

Pre-/postintervention design. Outcomes were assessed prior to the first intervention session and after the last session at week 5 postintervention. Translating research into practice model was used to implement the intervention in the two sites.

Primary outcomes:

• Cancer Support Distress Scale (CSSD) to assess emotional distress
• Functional Assessment of Cancer Treatment-General (FACT-G) to assess QOL

Secondary outcomes:

• Benefits of illness Scale to assess caregivers’ perceived benefits
• Lewis’ Cancer Self-efficacy Scale (CASE) to assess confidence to manage cancer
• Lewis’ Mutuality and Interpersonal Sensitivity Scale (MIS) to assess communication about cancer between patient and caregiver

Feasibility, satisfaction with program, and cost were also assessed. Feasibility was assessed by enrollment, retention, and intervention fidelity rates. Satisfaction was assessed by the FOCUS satisfaction instrument. Cost was assessed by multiplying hourly time estimates and median hourly wages for healthcare social workers in California and Ohio based on the U.S. Bureau of Labor statistics.

• Primary outcomes: FOCUS had significant positive effects on dyad (both caregiver and patient) QOL (p = 0.014), emotional well-being (p = 0.12), functional well-being (p = 0.049), and emotional distress (p = 0.002), but not on physical and social well-being. 
• Secondary outcomes: FOCUS has significant effect on benefits of illness (p = 0.13) and self-efficacy (p = 0.001), but not on dyadic communication. 
• Feasibility: FOCUS intervention program was feasible (enrollment rate 71.4% and retention rate 90%, intervention fidelity 85%).
• Satisfaction: High satisfaction among caregivers about helpfulness of intervention, length of sessions, and number of sessions. 
• Cost: Average cost estimates for oversight and delivery of one five-session FOCUS program with four dyads was $669.45 ($722.17 in California and $577.42 in Ohio).

In CSC, FOCUS intervention five-session, social-worker driven program is effective in improving caregivers’ (and patients’) outcomes. FOCUS appears to be feasible and acceptable with reasonable costs.

• Small sample (< 100)
• Risk of bias (no control group). 
• Risk of bias (sample characteristics)
• Intervention expensive, impractical, or training needs
• Other limitations/explanation: Administered by trained social worker/family therapist, not a nurse; nurses could be trained. Results reported as “a dyad,” not CG-specific. Authors justified no control group because three prior RCTs demonstrated efficacy of FOCUS and all showed significant positive impact.

FOCUS is an effective psychoeducational intervention that can be administered by someone trained on the intervention and can be administered successfully in CSC.