The latter statement was not supported by strong evidence

The latter statement was not supported by strong evidence. Our systematic review will update the current evidence on the use of immunoglobulin prophylaxis and may stimulate a re-evaluation of our current practice and practice guidelines. ABT 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/2test and I2statistic will also be calculated to evaluate heterogeneity. We will also use a visual inspection of a funnel plot to assess potential publication bias. == Discussion == 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. == Systematic review registration == PROSPERO CRD42015016684. Keywords:Immunoglobulin, Prophylaxis, Hematopoietic stem cell transplantation, clinical outcomes == Strengths and limitations of this study. == Rigorous study selection, data extraction, quality assessment and data synthesis. Predefined a priori sensitivity analyses. There may be a limited number of recent trials representing the haematopoietic stem cell transplantation population in the modern era. == Introduction == Haematopoietic stem cell transplantation (HSCT) is commonly employed in the management of a variety of malignancies.12High-dose chemotherapy and/or radiotherapy are given to maximise the tumouricidal effects, followed by the timely infusion of stem cells Rabbit polyclonal to AP4E1 to reconstitute the bone marrow and immune system. Pancytopaenia and immunodeficiency from therapy may cause potentially ABT fatal bacterial, viral or fungal infections such as cytomegalovirus (CMV) and immune complications such as graft-versus-host disease,35following transplantation. Intravenous immunoglobulin (IVIG) is a complex biological product with multiple potential mechanisms of action.6IVIG is used in many HSCT centres to prevent infectious complication post-HSCT.78For instance, at our centre, we have previously reported 31 and 13 doses of IVIG use during the first month post-HSCT in 77 autologous and 39 allogeneic transplant recipients.9CMV-specific immunoglobulin and plasma preparations are also available, and have been reported to be superior to polyvalent IVIG in the management of CMV infections.1011However, a recent systematic review of immunoglobulin prophylaxis did not demonstrate a mortality benefit but, rather, showed an increased risk of a veno-occlusive side effect.12Consequently, current societal guidelines do not recommend the routine use of immunoglobulin prophylaxis in recipients of HSCT.1314However, the clinical trials included in the previous systematic review were mostly published before the year 2000.12Further, there are other limitations in this review that deserve mention. First, the review included non-randomised studies;15second, some studies ABT only looked at biochemical surrogates, which may not correlate with patient relevant hard outcomes and, lastly, results from higher quality studies were not separately analysed, potentially introducing bias. Moreover, the landscape of patients receiving HSCT has evolved in the past decade. Patients undergoing HSCT are older and are more likely to be immunocompromised.16Further, HSCT technology including conditioning and chemosuppressive measures has also evolved.21719Finally, the technology of immunoglobulin production has evolved, resulting in intact IgG preparations with normal half-life and effector functions, and with higher pathogen safety.20Taken together, the prior available evidence may not be adequate to inform current HSCT practice. We seek to conduct a comprehensive systematic review of available evidence from prospective randomised controlled clinical trials assessing the use of immunoglobulins in HSCT that report clinically important end points. == Aims and objectives == Our overarching objective is to update, summarise and quantify the clinical effects of prophylactic immunoglobulins in the context of HSCT. Specifically, we seek to evaluate the utility of peri-HSCT use of IVIG on mortality, post-HSCT complications, infections and relapse post-HSCT. == Methods/design == == Search strategy == The systematic search strategy will include MEDLINE (1966 ABT to February 2015), EMBASE (1980 to February 2015) and all EBM Reviews (December 2014). A Dickersinet al21filter will be used to aid identification of randomised controlled trials (RCTs). A Google Scholar search will be performed in order to identify any grey literature. Studies relevant to animals but not to humans will be excluded. Publications, regardless of language, and of if they had been released as meeting proceedings irrespective, journals or abstracts, is going to be included.