• Systematic Review of the Pharmacogenomics of Cyclosporine, Methotrexate, and Tacrolimus as Prophylactic Agents Against Graft Vs. Host Disease in Allogeneic Hematopoietic Stem Cell Transplant

      Larriva, Marty; Campbell, Patrick; Ju, Hee; Kim, Gahyun; Ahn, David; College of Pharmacy, The University of Arizona (The University of Arizona., 2018)
      Purpose: Review available literature to determine any overlap in targeted genes associated with prophylactic agents and to review specific outcomes such as severity of Graft vs. Host Disease (GvHD). Methods: Using the GRADE approach, a systematic review was conducted by three investigators. Eligible studies had one of the followings in the title: methotrexate, cyclosporine, tacrolimus, pharmacogenomics, polymorphism, single nucleotide polymorphism (SNP), transplantation, allogeneic, or GvHD. A total of 15 databases were used including EMBASE, PubMed, AHRQ guideline search, BIOSIS, CINAHL, ClinicalTrial.gov, Cochrane Library, Global Health Library, IPA, National Guideline Clearinghouse, PharmGKB, Phenopedia, SciFinder, Scopus, and Web of Science. Main Results: From 15,907 of total search results, 15,484 was left after removing exact duplicates and 13,234 after removing close duplicates. 168 studies were left after title screening, 16 after abstract screening, and 7 after full text screening. The MTHFR CT/TT polymorphisms may reduce the incidence of GvHD. MTHFR and ATIC polymorphisms in CsA/MTX had a greater incidence of acute GvHD, while ABCC1 SNP had a decreased risk of acute GvHD. No pharmacogenomic association was found with FK. Conclusions: Reviewing the literatures from 16 databases on the pharmacogenomics of methotrexate, cyclosporine, and tacrolimus, we found that there may be a strong relationship between methylenetetrahydrofolate reductase (MTHFR) polymorphisms and GvHD outcomes when using methotrexate as a prophylactic agent. However, no consensus could be made regarding the relationship between cyclosporine or tacrolimus and their genes of interest due to lack evidence, and studies identified during the screening process.