Cyclophosphamide plus total body irradiation compared with busulfan plus cyclophosphamide as a conditioning regimen prior to hematopoietic stem cell transplantation in patients with leukemia: a systematic review and meta-analysis

BACKGROUND AND OBJECTIVESCyclophosphamide plus total body irradiation (CYTBI) and oral busulfan plus cyclophosphamide (BUCY) are commonly used conditioning regimens prior to allogeneic hematopoietic stem cell transplantation (HSCT) in patients with leukemia. However, there is conflicting data on the superiority of one regimen over the other. Our aim was to critically appraise and synthesize available evidence regarding the efficacy and safety of CYTBI compared to BUCY as a conditioning regimen.DESIGN AND SETTINGSystematic review and meta-analysis of randomized, controlled trials (RCTs) comparing BUCY with CYTBI.METHODSWe 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 disease-free survival (DFS). Acute and late toxicity were secondary endpoints. Meta-analysis was attempted only on RCTs. A relative risk or risk ratio (RR) and 95% confidence interval (CI) was calculated for each outcome in the meta-analysis.RESULTSFifteen non-randomized comparative studies involving 6280 patients were included in a narrative review without attempting a pooled analysis, in view of the potential for significant bias. Outcome data from seven RCTs involving 730 patients randomly assigned to either CYTBI or BUCY was pooled using meta-analytic methods. CYTBI was associated with a modest but non-significant reduction in all cause mortality (RR=0.82, 95%CL: 0.64–1.05; P=.12) and relapse of leukemia (RR=0.89, 95%CI: 0.72–1.10; P=.28). Transplant-related mortality (TRM) was significantly lesser with CYTBI compared to oral BUCY (RR-0.53, 95%CI: 0.31-0.90; P=.02). The cumulative incidence of major complications was not significantly different between the two regimens, but specific complications varied according to the conditioning regimen. TBi-based regimens were associated with more severe late effects on growth and development in children.CONCLUSIONThis analysis represents the largest comparative analyses of CYTBI with BUCY as a conditioning regimen prior to HSCT in the indexed medical literature. Conditioning regimen and disease (type and setting) can significantly affect outcomes. TRM is significantly lesser with CYTBI, but this does not translate into a significant survival benefit. There remain valid concerns regarding the late effects of TBI, particularly in children. Although not overly superior, the weight of evidence favors CYTBI over BUCY as a first choice-conditioning regimen in patients with leukemia