Graft-Versus-Host Disease Prophylaxis after Transplantation: A Network Meta-Analysis
Publication Date
December 08, 2014
Journal
PLOS ONE
Authors
Panayiotis D. Ziakas, Fainareti N. Zervou, Ioannis M. Zacharioudakis & Eleftherios Mylonakis
Volume
9
Issue
12
Pages
e114735
DOI
https://dx.plos.org/10.1371/journal.pone.0114735
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0114735
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/25485632
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4259365
Europe PMC
http://europepmc.org/abstract/MED/25485632
Web of Science
000346907600092
Scopus
84915827759
Mendeley
http://www.mendeley.com/research/graftversushost-disease-prophylaxis-after-transplantation-network-metaanalysis-2
Events
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Mendeley | Further Information

{"title"=>"Graft-versus-host disease prophylaxis after transplantation: A network meta-analysis", "type"=>"journal", "authors"=>[{"first_name"=>"Panayiotis D.", "last_name"=>"Ziakas", "scopus_author_id"=>"6506192206"}, {"first_name"=>"Fainareti N.", "last_name"=>"Zervou", "scopus_author_id"=>"56117744500"}, {"first_name"=>"Ioannis M.", "last_name"=>"Zacharioudakis", "scopus_author_id"=>"56117295900"}, {"first_name"=>"Eleftherios", "last_name"=>"Mylonakis", "scopus_author_id"=>"7005712035"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-84915827759", "pui"=>"600700970", "doi"=>"10.1371/journal.pone.0114735", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "sgr"=>"84915827759", "pmid"=>"25485632"}, "id"=>"f638f48b-c560-3b23-a45b-0a3a474e483d", "abstract"=>"BACKGROUND: Graft-versus-host Disease (GvHD) prophylaxis after allogeneic hematopoietic stem-cell transplantation (HSCT) is an ongoing effort but relative effects of different policies are not systematically explored.\\n\\nMETHODS: We systematically reviewed 30-year evidence on GvHD prophylaxis and quantified the relative effect of different policies using a network meta-analysis. We searched PubMed and the Cochrane Library for randomized studies on the topic. The primary outcome of interest was grade II-IV acute GvHD over 0 or I (with odds ratio OR <1 denoting benefit).\\n\\nFINDINGS: Thirty-three eligible studies that enrolled 3,440 patients (published up to June 2014), provided data on seven immunosuppressive drugs namely cyclosporin A (CsA), methotrexate (MTX), anti-thymocyte globulin (ATG), mycophenolate mofetil (MMF), tacrolimus, sirolimus or corticosteroids and their combinations to calculate 14 direct and 21 indirect effects. The majority of trials (32/33) referred to myeloablative conditioning and sibling transplants (25/33). Tacrolimus/MTX (OR 0.44; 95% 0.27-0.70, number needed to treat to benefit, i.e. to avert a case of II-IV GvHD, NNTB = 5) and ATG/CsA/MTX (OR 0.45; 95%CI 0.26-0.78; NNTB = 5) were superior over CsA/MTX. ATG/CsA/MTX did not differ from tacrolimus/MTX (indirect evidence). Sirolimus-based prophylaxis outperformed CsA/MTX (OR 0.10; 95%CI 0.02-0.49, NNTB = 4) and marginally outperformed tacrolimus/MTX (OR 0.22; 95%CI 0.05-1.11). Add-on corticosteroids had no benefit over CsA/MTX.\\n\\nCONCLUSIONS: Tacrolimus/MTX and ATG/CsA/MTX were the outperformers over CsA/MTX, but sirolimus-based regimens showed also potential. More randomized data are needed for reduced-intensity conditioning, as well as for MMF and sirolimus-containing regimens.", "link"=>"http://www.mendeley.com/research/graftversushost-disease-prophylaxis-after-transplantation-network-metaanalysis-2", "reader_count"=>17, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Student > Doctoral Student"=>2, "Researcher"=>1, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>3, "Other"=>2, "Student > Master"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Student > Doctoral Student"=>2, "Researcher"=>1, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>3, "Other"=>2, "Student > Master"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Mathematics"=>1, "Medicine and Dentistry"=>7, "Pharmacology, Toxicology and Pharmaceutical Science"=>4, "Chemistry"=>1, "Immunology and Microbiology"=>2, "Nursing and Health Professions"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>7}, "Chemistry"=>{"Chemistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Mathematics"=>{"Mathematics"=>1}, "Unspecified"=>{"Unspecified"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>4}}, "reader_count_by_country"=>{"Czech Republic"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1830153"], "description"=>"<p>(The complete study characteristics are available on S1 Table in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0114735#pone.0114735.s001\" target=\"_blank\">S1 Appendix</a>).</p><p>CsA = cyclosporine A; MTX = methotrexate; ATG = antithymocyte globulin; MP = methyl-prednisolone; Pse = systemic corticosteroid (prednisolone or methylprednisolone); BDP =  oral beclomethasone propionate. MMF =  mycophenolate mofetil, NR = not reported.</p><p>Summary of included studies and stratified prophylaxis data on outcome.</p>", "links"=>[], "tags"=>["policy", "benefit", "myeloablative conditioning", "corticosteroids", "csa", "hsct", "atg", "odds ratio", "ci", "regimen", "Cochrane library", "mmf", "randomized studies", "randomized data", "evidence", "NNTB", "GVHD prophylaxis", "tacrolimu", "mtx"], "article_id"=>1264640, "categories"=>["Biological Sciences"], "users"=>["Panayiotis D. Ziakas", "Fainareti N. Zervou", "Ioannis M. Zacharioudakis", "Eleftherios Mylonakis"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0114735.t001", "stats"=>{"downloads"=>2, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Summary_of_included_studies_and_stratified_prophylaxis_data_on_outcome_/1264640", "title"=>"Summary of included studies and stratified prophylaxis data on outcome.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-12-08 03:12:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/1830154"], "description"=>"<p>Summary of indirect effects for the primary outcome (II-IV GvHD).</p>", "links"=>[], "tags"=>["policy", "benefit", "myeloablative conditioning", "corticosteroids", "csa", "hsct", "atg", "odds ratio", "ci", "regimen", "Cochrane library", "mmf", "randomized studies", "randomized data", "evidence", "NNTB", "GVHD prophylaxis", "tacrolimu", "mtx"], "article_id"=>1264641, "categories"=>["Biological Sciences"], "users"=>["Panayiotis D. Ziakas", "Fainareti N. Zervou", "Ioannis M. Zacharioudakis", "Eleftherios Mylonakis"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0114735.t002", "stats"=>{"downloads"=>5, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Summary_of_indirect_effects_for_the_primary_outcome_II_IV_GvHD_/1264641", "title"=>"Summary of indirect effects for the primary outcome (II-IV GvHD).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-12-08 03:12:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/1830157"], "description"=>"<div><p>Background</p><p>Graft-versus-host Disease (GvHD) prophylaxis after allogeneic hematopoietic stem-cell transplantation (HSCT) is an ongoing effort but relative effects of different policies are not systematically explored.</p><p>Methods</p><p>We systematically reviewed 30-year evidence on GvHD prophylaxis and quantified the relative effect of different policies using a network meta-analysis. We searched PubMed and the Cochrane Library for randomized studies on the topic. The primary outcome of interest was grade II-IV acute GvHD over 0 or I (with odds ratio OR <1 denoting benefit).</p><p>Findings</p><p>Thirty-three eligible studies that enrolled 3,440 patients (published up to June 2014), provided data on seven immunosuppressive drugs namely cyclosporin A (CsA), methotrexate (MTX), anti-thymocyte globulin (ATG), mycophenolate mofetil (MMF), tacrolimus, sirolimus or corticosteroids and their combinations to calculate 14 direct and 21 indirect effects. The majority of trials (32/33) referred to myeloablative conditioning and sibling transplants (25/33). Tacrolimus/MTX (OR 0.44; 95% 0.27–0.70, number needed to treat to benefit, i.e. to avert a case of II-IV GvHD, NNTB = 5) and ATG/CsA/MTX (OR 0.45; 95%CI 0.26–0.78; NNTB = 5) were superior over CsA/MTX. ATG/CsA/MTX did not differ from tacrolimus/MTX (indirect evidence). Sirolimus-based prophylaxis outperformed CsA/MTX (OR 0.10; 95%CI 0.02–0.49, NNTB = 4) and marginally outperformed tacrolimus/MTX (OR 0.22; 95%CI 0.05–1.11). Add-on corticosteroids had no benefit over CsA/MTX.</p><p>Conclusions</p><p>Tacrolimus/MTX and ATG/CsA/MTX were the outperformers over CsA/MTX, but sirolimus-based regimens showed also potential. More randomized data are needed for reduced-intensity conditioning, as well as for MMF and sirolimus-containing regimens.</p></div>", "links"=>[], "tags"=>["policy", "benefit", "myeloablative conditioning", "corticosteroids", "csa", "hsct", "atg", "odds ratio", "ci", "regimen", "Cochrane library", "mmf", "randomized studies", "randomized data", "evidence", "NNTB", "GVHD prophylaxis", "tacrolimu", "mtx"], "article_id"=>1264644, "categories"=>["Biological Sciences"], "users"=>["Panayiotis D. Ziakas", "Fainareti N. Zervou", "Ioannis M. Zacharioudakis", "Eleftherios Mylonakis"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0114735", "stats"=>{"downloads"=>4, "page_views"=>21, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Graft_Versus_Host_Disease_Prophylaxis_after_Transplantation_A_Network_Meta_Analysis_/1264644", "title"=>"Graft-Versus-Host Disease Prophylaxis after Transplantation: A Network Meta-Analysis", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-12-08 03:12:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/1830146"], "description"=>"<p>The thickness of connecting lines is proportional to the number of available direct comparisons.</p>", "links"=>[], "tags"=>["policy", "benefit", "myeloablative conditioning", "corticosteroids", "csa", "hsct", "atg", "odds ratio", "ci", "regimen", "Cochrane library", "mmf", "randomized studies", "randomized data", "evidence", "NNTB", "GVHD prophylaxis", "tacrolimu", "mtx"], "article_id"=>1264633, "categories"=>["Biological Sciences"], "users"=>["Panayiotis D. Ziakas", "Fainareti N. Zervou", "Ioannis M. Zacharioudakis", "Eleftherios Mylonakis"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0114735.g001", "stats"=>{"downloads"=>10, "page_views"=>27, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Network_of_direct_solid_lines_and_indirect_comparisons_dashed_lines_of_different_treatments_evaluated_for_acute_GvHD_prophylaxis_/1264633", "title"=>"Network of direct (solid lines) and indirect comparisons (dashed lines) of different treatments evaluated for acute GvHD prophylaxis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-12-08 03:12:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/1830148"], "description"=>"<p>Forest plot of direct comparisons for the primary outcome (II-IV GvHD).</p>", "links"=>[], "tags"=>["policy", "benefit", "myeloablative conditioning", "corticosteroids", "csa", "hsct", "atg", "odds ratio", "ci", "regimen", "Cochrane library", "mmf", "randomized studies", "randomized data", "evidence", "NNTB", "GVHD prophylaxis", "tacrolimu", "mtx"], "article_id"=>1264635, "categories"=>["Biological Sciences"], "users"=>["Panayiotis D. Ziakas", "Fainareti N. Zervou", "Ioannis M. Zacharioudakis", "Eleftherios Mylonakis"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0114735.g002", "stats"=>{"downloads"=>1, "page_views"=>24, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Forest_plot_of_direct_comparisons_for_the_primary_outcome_II_IV_GvHD_/1264635", "title"=>"Forest plot of direct comparisons for the primary outcome (II-IV GvHD).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-12-08 03:12:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/1830151"], "description"=>"<p>Forest plot of direct comparisons for the secondary outcome (III-IV GvHD).</p>", "links"=>[], "tags"=>["policy", "benefit", "myeloablative conditioning", "corticosteroids", "csa", "hsct", "atg", "odds ratio", "ci", "regimen", "Cochrane library", "mmf", "randomized studies", "randomized data", "evidence", "NNTB", "GVHD prophylaxis", "tacrolimu", "mtx"], "article_id"=>1264638, "categories"=>["Biological Sciences"], "users"=>["Panayiotis D. Ziakas", "Fainareti N. Zervou", "Ioannis M. Zacharioudakis", "Eleftherios Mylonakis"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0114735.g003", "stats"=>{"downloads"=>1, "page_views"=>27, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Forest_plot_of_direct_comparisons_for_the_secondary_outcome_III_IV_GvHD_/1264638", "title"=>"Forest plot of direct comparisons for the secondary outcome (III-IV GvHD).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-12-08 03:12:41"}

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Relative Metric

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