title: Protocol for updating a systematic review of randomised controlled trials on the prophylactic use of intravenous immunoglobulin for patients undergoing haematopoietic stem cell transplantation.
abstract: BACKGROUND
  Haematopoietic stem cell transplantation (HSCT) is commonly employed in the management of haematological malignancies. This intervention results in an increased risk of infectious and immune-related complications. Prophylactic immunoglobulin therapy has been used to prevent post-HSCT complications, including infections, with varying efficacy. We sought to update the current evidence supporting the use of immunoglobulins in the modern HSCT era.
  
  
  METHODS
  Using a structured search strategy, we will perform a systematic review of the literature from MEDLINE, EMBASE and all EBM Reviews databases. We will include randomised clinical trials investigating clinical outcomes of prophylactic polyvalent immunoglobulin or cytomegalovirus (CMV)-specific immunoglobulin or plasma in patients undergoing HSCT. Clinical outcomes will include overall survival, transplant-related mortality, CMV infection, CMV disease, graft-versus-host disease, interstitial pneumonitis/fibrosis and hepatic veno-occlusive disease. Studies that only reported the results of biochemical tests will be excluded. Data will be extracted by two investigators independently. Study quality assessment will be evaluated using a validated five-point system as proposed by Jadad. Trial quality will be further assessed by identifying whether there was adequate allocation concealment. Where appropriate, a meta-analysis will be performed where relative risk will be used as the primary summary measure with 95% CIs. Pooled measures will be calculated for randomised clinical trials using a random-effects model. The Cochrane Q/χ(2) test and I(2) statistic will also be calculated to evaluate heterogeneity. We will also use a visual inspection of a funnel plot to assess potential publication bias.
  
  
  CONCLUSIONS
  This systematic review aims to provide current evidence to justify the use of immunoglobulin prophylaxis in HSCT recipients. We will discuss whether current HSCT guidelines are supported by the current evidence, and whether further trials are needed, given the changing landscape of patients undergoing HSCT and the immunoglobulin manufacturing process.
  
  
  BACKGROUND
  PROSPERO CRD42015016684.
authors: Division of Infectious Diseases, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors: Juthaporn
authors: J
authors: Cowan
authors: Division of Infectious Diseases, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors: D W
authors: DW
authors: Cameron
authors: Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada Renal Transplantation, Division of Nephrology, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors: Greg
authors: G
authors: Knoll
authors: Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada Blood and Marrow Transplant Program, The Ottawa Hospital, Ottawa, Ontario, Canada.
authors: Jason
authors: J
authors: Tay
mesh_terms: D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage*; D015201:Meta-Analysis as Topic; D011183:Postoperative Complications / Q000517:prevention & control*; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D018570:Risk Assessment; D000078202:Systematic Reviews as Topic; D016896:Treatment Outcome
chemical_list: D016756:Immunoglobulins, Intravenous
keywords: Hematopoietic stem cell transplantation; Immunoglobulin; Prophylaxis; clinical outcomes