Article

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

Center and Division for Evidence Based Medicine and Health Outcomes Research, Department of Internal Medicine, College of Medicine, University of South Florida, Tampa, FL 33612, USA.
Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K (Impact Factor: 9.38). 12/2011; 26(4):582-8. DOI: 10.1038/leu.2011.349
Source: PubMed

ABSTRACT 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.

0 Followers
 · 
123 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: This retrospective analysis compared two regimens of fludarabine combined with i.v. BU 6.4 mg/kg (FB2) or BU 12.8 mg/kg (FB4) for allografting of AML in first CR. A total of 437 patients (median age: 50 years) were administered FB2 (n=225, 51%) or FB4 (n=212, 49%). Median follow-up time was 28 months. Use of FB2 resulted in a longer time to neutrophil engraftment (17 vs 15 days, P<0.0001) but no difference in incidence of grade II-IV acute (P=0.54) or chronic GVHD (P=0.51). In patients <50 years of age, FB2 was associated with a higher 2-year cumulative incidence of relapse (33±6% vs 20±4%, P=0.04), but there was no difference in 2-year leukemia-free survival (LFS) (P=0.45), OS (P=0.53) or non-relapse mortality (P=0.17). In recipients ⩾50 years of age, FB2 resulted in better 2-year LFS (63±4% vs 42±7%, P=0.02) and OS (68±4% vs 45±7%, P=0.006); a lower 2-year non-relapse mortality, albeit not statistically significant (15±3% vs 29±6%, P=0.06), was observed with FB2. FB2 is an effective and well-tolerated regimen in patients ⩾50 years of age and does not compromise survival when used in patients <50 years undergoing allogeneic transplantation for AML in first CR.Bone Marrow Transplantation advance online publication, 30 June 2014; doi:10.1038/bmt.2014.133.
    Bone Marrow Transplantation 06/2014; 49(9). DOI:10.1038/bmt.2014.133 · 3.47 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Hematopoietic cell transplantation (HCT) represents the most common and effective form of immunotherapy for childhood malignancies. The role of the graft-versus-leukemia effect in allogeneic HCT has been well established in childhood malignancies, but is also associated with short-term and long-term morbidity. HCT may be ineffective in some settings at obtaining control of the malignancy, and as such, cannot be used as a universal cancer immunotherapy. Novel therapies using dendritic cell vaccinations, tumor-infiltrating lymphocytes, and chimeric antigen receptor T cells are being evaluated as potential adjuvants to HCT. Copyright © 2015 Elsevier Inc. All rights reserved.
    Pediatric Clinics of North America 02/2015; 62(1):257-273. DOI:10.1016/j.pcl.2014.10.001 · 2.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Encouraging results have been reported with sirolimus, tacrolimus and low-dose methotrexate after non-myeloablative allogeneic hematopoietic cell transplant. We conducted a retrospective analysis of 71 patients with lymphoid malignancies treated with this prophylaxis regimen after non-myeloablative or reduced intensity allogeneic hematopoietic cell transplant. Grafts were human leukocyte antigen (HLA)-matched related in 29 (41%), matched unrelated in 36 (51%) and 9/10 HLA-matched unrelated in six (8%) patients. The regimen was well tolerated and over 90% of patients completed the planned treatment. The cumulative incidences of 1-year grade B–D and C–D acute graft-versus-host disease (GVHD) were 0.28 (95% confidence interval [CI], 0.18–0.39) and 0.07 (95% CI, 0.03–0.15), respectively, and of 1- and 2-year chronic GVHD (National Institutes of Health criteria) in 70 evaluable patients were 0.15 (95% CI, 0.08–0.24) and 0.33 (95% CI, 0.22–0.44), respectively. The median day of onset of acute GVHD was 123 days (range, 17–268 days). Peri-transplant rituximab or anti-thymocyte globulin did not affect GVHD. The cumulative incidence of 1-year non-relapse mortality and relapse were 4% and 20%, respectively. With a median follow-up of 3.5 (range: 0.18–5.1) years, overall survival and progression-free survival at 2 years were 82% and 66%, respectively. This GVHD regimen results in a low incidence and severity of acute and chronic GVHD after reduced intensity and non-myeloablative allogeneic hematopoietic cell transplant for lymphoid malignancies. The study also highlights the incidence of late onset acute GVHD in non-myeloablative/reduced intensity conditioning, and the contribution of the new GVHD staging system that more accurately reflects clinical outcomes.
    Leukemia and Lymphoma 08/2014; 56(3). DOI:10.3109/10428194.2014.930851 · 2.61 Impact Factor