Search for Existing Guidelines
A search for existing guidelines is generally undertaken prior to searching for existing systematic reviews or primary literature. This is done with the goal of identifying existing guidelines for adaptation, using the ADAPTE framework, or endorsement in order to avoid the duplication of guideline development efforts across jurisdictions. For this document, the following sources were searched for existing guidelines that addressed the research questions:
- Practice Guideline Databases:
- Electronic Databases: MEDLINE and EMBASE
Guidelines that were considered relevant to the objectives and the research questions were then evaluated for quality using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. Two guidelines were identified as potentially relevant and considered for full text review and quality assessment using the AGREE II instrument. However, the reporting quality was low, taking into consideration the methods used to search for the evidence, the methods used to formulate the recommendations, and the criteria for selecting the evidence. In addition stakeholder involvement, among other domains needed for undergoing quality assurance, was not reported. For these reasons, the recommendations made in these two guidelines were not considered for endorsement or adaptation and no quality assessment was conducted.
This evidence review was conducted in two planned stages, including a search for systematic reviews followed by a search for primary literature.
Search for Existing Systematic Reviews
The Cochrane Database of Systematic Reviews was searched from January 2009 to April 2014 using the word "plerixafor". Systematic reviews older than six years were considered not relevant, because the main goal of a search for systematic reviews is to identify recent secondary sources covering the primary literature that may be helpful in the development of these recommendations.
Systematic reviews were included if:
- The existing systematic review searched for studies evaluating the efficacy of plerixafor in enhancing hematopoietic stem cell mobilization and collection in adult or pediatric patients considered for autologous stem cell transplantation (SCT)
- The literature search strategy for the existing review was reproducible and appropriate
- The existing systematic review reported the sources searched as well as the dates that were searched
Identified systematic reviews that met the eligibility criteria would be assessed using the Assessing Methodological Quality of Systematic Reviews (AMSTAR) tool (a measurement tool to assess the methodological quality of systematic reviews) to determine whether or not an existing review could be incorporated as part of the evidentiary base. Any identified reviews that did not meet the criteria above, whose AMSTAR assessments indicated important deficiencies in quality, or that were otherwise not incorporated as part of the evidence base would be reported in the reference list, but not further described or discussed.
Search for Primary Literature
Literature Search Strategy
The MEDLINE (Ovid) (1996 through April 18, 2014) and EMBASE (Ovid) (1996 through Week 16, 2014) databases were searched for evidence in April 2014 and updated in March 2015. The search strategy included a logical combination of terms for the condition (stem cell transplantation), the intervention (plerixafor), and studies of interest (systematic reviews, clinical trials, nonrandomized studies with an appropriate control group). The full literature strategy used to retrieve potential relevant studies is presented in Appendix 1 of the original guideline document.
Study Selection Criteria and Protocol
Articles identified in this literature search were eligible for inclusion if they met the following criteria:
- Primary studies evaluating the efficacy of plerixafor in enhancing hematopoietic stem cell mobilization and collection before autologous SCT
- Published full-report articles of randomized control trials and nonrandomized studies with an appropriate contemporaneous control group
- Studies reporting the outcomes of interest such as number of CD34+ cells collected, number of apheresis procedures, proportion of patients who proceed to autologous SCT, and survival rate post-SCT
Studies were excluded if they were:
- Abstracts, letters, case reports, comments, books, notes, or editorial-type publications
- Because resources were not available for translation services, articles published in a language other than English
A review of the titles and abstracts that resulted from the search was conducted by one reviewer, and the reference list from these sources was searched for additional trials. For those items that warranted full text review, the same reviewer assessed each item independently.
Search for Existing Systematic Reviews
The Cochrane Collaboration released a systematic review protocol in 2013 to evaluate the efficacy and safety of plerixafor for the mobilization of hematopoietic stem cells in people with non-Hodgkin lymphoma, Hodgkin lymphoma, or multiple myeloma and with the indication for autologous transplantation, but a full report has not been published yet. No other relevant systematic reviews were identified.
Systematic Review of the Primary Literature
Literature Search Results
While reviewing the primary literature few studies were identified that met the initial inclusion criteria, and therefore a post hoc subset of nonrandomized studies with historical groups was included, because these types of studies would help to inform the recommendations. Similarly, due to the shortage of comparative studies assessing the efficacy of plerixafor in both patients failing mobilization prior to autologous SCT, and patients who have failed a prior mobilization regimen, the inclusion criteria for this population was expanded to include single-arm studies with a sample size of at least 30 participants.
As presented in Figure 1 of the original guideline document, out of 2576 titles and abstracts identified in the search of the MEDLINE and EMBASE databases, 2302 appeared potentially eligible on initial review, and 160 of these were verified to be eligible for full text review. Eight additional studies were included for full text review based on the updated search in 2015. From these, 22 full-report studies were identified that evaluated the efficacy of plerixafor in enhancing hematopoietic stem cell mobilization and collection before autologous SCT, and reported the outcome of interest. The remaining 146 studies were excluded because they failed to pass the inclusion criteria.