High-dose therapy and autologous hematopoietic cell transplantation as front-line consolidation in chronic lymphocytic leukemia: a systematic review.

High-dose therapy (HDT) followed by autologous hematopoietic cell transplantation (auto-HCT) is offered to patients with chronic lymphocytic leukemia (CLL) both as front-line consolidation and in the relapsed setting. The role of HDT in the front-line consolidation setting in CLL is uncertain. Literature search of PUBMED and Cochrane until 14 November 2014 and the last 2 years of abstracts from relevant conferences was undertaken. End points included benefits (overall survival; OS, PFS, event-free survival; EFS) and harms (adverse events, secondary malignancies, treatment-related mortality). The search identified 495 references of which four studies met inclusion criteria. Altogether, 301 patients were randomized to the HDT/auto-HCT arm and 299 patients to the control arm. Offering front-line HDT/auto-HCT did not result in statistically significant improvement in OS (Hazard ratio (HR)=0.91; 95% confidence interval (CI)= 0.62, 1.33) or PFS (HR=0.70; 95% CI= 0.32, 1.52). There was a statistically significant advantage favoring HDT/auto-HCT for EFS (HR=0.46; 95% CI= 0.26, 0.83). Moreover, HDT/auto-HCT did not result in higher rate of secondary malignancy (risk ratio=1.06; 95% CI=0.55, 2.05) or treatment-related mortality (risk ratio=1.32; 95% CI= 0.43, 4.06). Offering HDT/auto-HCT as front-line consolidation in patients with CLL does not improve OS. At present this approach should not be offered outside the context of a clinical trial.

Antithymocyte globulin for acute-graft-versus-host-disease prophylaxis in patients undergoing allogeneic hematopoietic cell transplantation: a systematic review.

Graft-versus-host-disease (GVHD) is a major complication associated with allogeneic hematopoietic cell transplantation (allo-HCT). Antithymocyte globulin (ATG) is recommended for GVHD prophylaxis following allo-HCT, however, evidence on efficacy of ATG is conflicting. Accordingly, we undertook a systematic review. All phase III randomized controlled trials (RCTs) comparing ATG versus control for prevention of GVHD in patients undergoing allo-HCT were eligible. Medline and Cochrane databases were searched. Data on methodological quality, benefits and harms were extracted for each trial and pooled under a random effects model. Seven RCTs enrolling 733 patients met inclusion criteria. Pooled results showed no difference for overall survival with use of ATG (hazard ratio was 0.91; 95% confidence intervals (CI), 0.75-1.10; P = 0.32). There was a significant benefit for prevention of grade III/IV acute GVHD (risk ratio (RR) = 0.51; 95% CI, 0.27-0.94; P = 0.03). There was no benefit associated with ATG use for prevention of either grade II (RR = 0.79; 95% CI, 0.48-1.30; P = 0.35) or grade I acute GVHD (RR = 1.42; 95% CI, 0.75-2.69; P = 0.28). Use of ATG was not associated with significant reduction in non-relapse mortality (RR = 0.74; 95% CI, 0.53-1.03; P = 0.08). Future trials with adequate sample size are required to provide more definitive answers.