Alternative-Donor Hematopoietic Stem Cell Transplantation for Sickle Cell Disease in Pediatric Patients: A Systematic Review and Meta-Analysis

Background Allogeneic hematopoietic stem cell transplantation (HSCT) from HLA-matched sibling donor for patients with sickle cell disease (SCD) provides excellent curative potential with acceptable rates of graft rejection and other common post transplant complications. However, in the United States, only 18% of patients with SCD have an HLA-matched sibling donor. Hence, multiple studies adopted various strategies to figure out alternative donors with favorable outcomes. Poor engraftment, graft versus host disease (GVHD) and regimen related toxicities are the main obstacles following alternative-donor transplant. To overcome these complications, different modalities had been experimented targeting the source of the stem cell, CD34 and TNC cell counts, pre-transplant conditioning regimens and adding immunosuppressive drugs pre/post transplant. However, so far there is no worldwide consensus about robust strategy for alternative donor HSCT. Aim The aim of this review is to systematically evaluate the outcomes of alternative-donor HSCT in patients with SCD in pediatric population, and correlate the outcomes with experimented interventional regimens. Methods We searched PubMed, SCOPUS, Embase, Cochrane and Clinical trials.gov from 2000 till February 2018. We utilized the Systematic Reviews and Meta-Analyses guidelines for Preferred Reporting Results (PRISMA). Two reviewers independently screened titles/abstracts, assessed full-text articles, extracted data from included articles, and assessed their quality. Risk of bias in the included studies was assessed using ROBINS-I tool. Data of platelet/neutrophil recovery, acute/chronic GvHD incidence and overall survival were pooled in a single-arm meta-analysis approach. Results Of the 2886 records examined, 19 met predefined criteria. 16 studies were included in the meta-analysis. 12 clinical trials, 5 cohort observational studies and 2 case reports. All studies had a sample size