Prophylaxis with Sirolimus and Tacrolimus ± Antithymocyte Globulin Reduces the Risk of Acute Graft-versus-Host Disease without an Overall Survival Benefit Following Allogeneic Stem Cell Transplantation

被引:30
|
作者
Rosenbeck, Lindsay L. [1 ,2 ]
Kiel, Patrick J. [1 ,2 ]
Kalsekar, Iftekhar [4 ]
Vargo, Craig [2 ]
Baute, John [1 ]
Sullivan, Cheryl K. [1 ]
Wood, Lisa [1 ]
Abdelqader, Sahar [1 ]
Schwartz, Jennifer [1 ,3 ]
Srivastava, Shivani [1 ,3 ]
Abonour, Rafat [1 ,3 ]
Robertson, Michael J. [1 ,3 ]
Nelson, Robert P., Jr. [1 ,3 ]
Cornetta, Kenneth [1 ,3 ]
Fausel, Christopher A. [1 ,3 ]
Farag, Sherif S. [1 ,3 ]
机构
[1] Indiana Univ Simon Canc Ctr, Indianapolis, IN 46202 USA
[2] Indiana Univ Sch Med, Dept Pharm, Indianapolis, IN USA
[3] Indiana Univ Sch Med, Dept Internal Med, Indianapolis, IN USA
[4] Butler Univ, Dept Pharm Practice, Indianapolis, IN 46208 USA
关键词
Sirolimus; Tacrolimus; Graft-versus-host disease; Stem cell transplant; Sinusoidal obstructive syndrome; BONE-MARROW-TRANSPLANTATION; COMPARING METHOTREXATE; VENOOCCLUSIVE DISEASE; CYCLOSPORINE; RAPAMYCIN; INHIBITION; BLOCKADE; LEUKEMIA; LIVER;
D O I
10.1016/j.bbmt.2010.09.017
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Methotrexate (MIX) is a standard agent used in combination with calcineurin inhibitors for graft-versus-host disease (GVHD) prophylaxis in patients undergoing allogeneic hematopoietic cell (HCT) transplantation. We retrospectively compared the incidence of acute GVHD (aGVHD), transplant-related morbidity, and mortality in patients given sirolimus/tacrolimus +/- antithymocyte globulin (ATG) versus MTX/tacrolimus or cyclosporine and allogeneic transplantation for hematologic malignancies. Between January 1, 2005, and April 30, 2009, 106 consecutive patients received peripheral blood HCT or bone marrow grafts after 1 of 6 myeloablative conditioning regimens. The incidence of grade II-IV aGVHD was 18.6% in patients who received sirolimus/tacrolimus compared to 48.9% who received MIX (P = .001). The incidence of grade III-IV aGVHD was 5% and 17% (P = .045), respectively. There was no difference in overall survival (OS) between the groups (P = .160). Chronic GVHD (cGVHD) occurred in 40.4% who received sirolimus and 41.9% receiving MIX (P = .89). The incidence of thrombotic microangiopathy or interstitial pneumonitis was not significantly different between groups. The reduction in the risk of severe aGVHD was offset by an increased (20% versus 4%, P = .015) incidence of and mortality from sinusoidal obstructive syndrome (SOS). Sirolimus/tacrolimus appears to reduce the incidence of aGVHD after conventional allotransplantion compared to MTX-calcineurin inhibitor prophylaxis; however, this did not improve survival. Biol Blood Marrow Transplant 17: 916-922 (2011) (C) 2011 American Society for Blood and Marrow Transplantation
引用
收藏
页码:916 / 922
页数:7
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