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. 2012 Nov;18(11):1734-44.
doi: 10.1016/j.bbmt.2012.06.004. Epub 2012 Jun 16.

Anti-thymocyte globulin (thymoglobulin), tacrolimus, and sirolimus as acute graft-versus-host disease prophylaxis for unrelated hematopoietic stem cell transplantation

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Anti-thymocyte globulin (thymoglobulin), tacrolimus, and sirolimus as acute graft-versus-host disease prophylaxis for unrelated hematopoietic stem cell transplantation

Zaid Al-Kadhimi et al. Biol Blood Marrow Transplant. 2012 Nov.

Abstract

Acute graft-versus-host disease (aGVHD) is a major cause of morbidity and mortality in patients undergoing unrelated hematopoietic stem cell transplantation. We prospectively evaluated the efficacy of intermediate-dose rabbit anti-thymocyte globulin (Thymoglobulin® a total of 4.5 mg/kg given over days -3, -2, and -1) in combination with tacrolimus and sirolimus for the prevention of aGVHD. We enrolled 47 recipients who underwent unrelated hematopoietic stem cell transplantation. Patients received daily granulocyte colony-stimulating factor starting on day +6 until neutrophil engraftment (median duration, 11 days; range, 9-15 days). Twenty-two patients received HLA 8/8 and 25 received 7/8 matched grafts, respectively. The median follow-up duration was 23.6 months (range, 18.8-27.9 months). The cumulative incidence of grade II to IV aGVHD was 23.4% (95% confidence interval, 12.4-36.3). At 2-year follow-up, the cumulative incidence of nonrelapse mortality was 31.9%, cumulative incidence of relapse was 24.6%, and cumulative incidence of chronic GVHD was 33%. Progression-free survival at 1 year was 54%, with a median of 17.7 months. Overall survival at 1 year was 65%, with no median reached. These results suggest that the combination of Thymoglobulin, tacrolimus, and sirolimus in patients undergoing unrelated hematopoietic stem cell transplantation is well tolerated and associated with a low incidence and severity of aGVHD and chronic graft-versus-host disease.

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Figures

Figure 1
Figure 1
Cumulative incidence of acute graft-versus-host disease (aGVHD) after unrelated hematopoietic stem cell transplantation. Panel A shows grade II-IV aGVHD. Panel B shows grade III-IV aGVHD.
Figure 2
Figure 2
Cumulative incidence of chronic graft-versus-host disease (cGVHD). UHSCT, unrelated hematopoietic stem cell transplantation.
Figure 3
Figure 3
Cumulative incidence of nonrelapse mortality. UHSCT, unrelated hematopoietic stem cell transplantation.
Figure 4
Figure 4
Cumulative incidence of relapse. UHSCT, unrelated hematopoietic stem cell transplantation.
Figure 5
Figure 5
Progression-free survival (PFS) and overall survival (OS). BMT, bone marrow transplantation.

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