Busulfan plus fludarabine compared with busulfan plus cyclophosphamide as a conditioning regimen prior to hematopoietic stem cell transplantation in patients with hematologic neoplasms: a meta-analysis

摘要

Objectives: The aim of the article is to critically appraise and synthesize available evidence regarding the efficacy and regimen-related toxicity (RRT) of Busulfan plus fludarabine (BuFlu) compared to busulfan plus cyclophosphamide (BuCy) as a conditioning regimen, prior to allogeneic hematopoietic stem cell transplantation (HSCT) in patients with hematologic neoplasms. Methods: A meta-analysis was attempted on clinical controlled trials (CCTs), randomized or non-randomized controlled trials (RCTs or non-RCTs), comparing BuCy with BuFlu. We did a systematic search of the indexed medical literature using appropriate keywords to identify potentially relevant articles. The primary outcome of interest was efficacy measured by overall survival (OS) and event-free survival (EFS), acute graft-versus-host-disease (aGVHD). Chronic GVHD (extensive) and other toxicity were secondary endpoints. A relative risk or risk ratio (RR) and 95% confidence interval (CI) was calculated for each outcome in the meta-analysis. Results: Nine clinical controlled trials were included, of which 4 tries were RCTs involving 584 patients and the other 5 were non-RCTs involving 571 patients. The cumulative incidences of OS, EFS, acute graft-versus-host disease (aGVHD) were not significantly different between the two regimens. The non-relapse mortality was higher in BuCy but non-significant increment (RR=1.48, 95% CI: [0.97-2.26]). Liver related toxicity was significantly higher with BuCy compared to BuFlu (RR=1.90, 95% CI: [1.00-3.61]). Conclusion: Liver related toxicity is significantly lesser with BuFlu, but BuFlu regimen has no significant benefits compared with BuCy in OS, EFS, aGVHD. For all this, the weight of evidence favors BuFlu over BuCy as a first choice-conditioning regimen for patients with hematologic neoplasms, especially for people who have poor liver function.