Sirolimus, tacrolimus, and low-dose methotrexate for graft-versus-host disease prophylaxis in mismatched related donor or unrelated donor transplantation

被引：130

作者：

Antin, JH ^{[1
]}

Kim, HT ^{[1
]}

Cutler, C ^{[1
]}

Ho, VT ^{[1
]}

Lee, SJ ^{[1
]}

Miklos, DB ^{[1
]}

Hochberg, EP ^{[1
]}

Wu, CJ ^{[1
]}

Alyea, EP ^{[1
]}

Soiffer, RJ ^{[1
]}

机构：

[1] Brigham & Womens Hosp, Dept Med, Dana Farber Canc Inst, Dept Med Oncol & Biostat Sci, Boston, MA 02115 USA

来源：

BLOOD | 2003年 / 102卷 / 05期

关键词：

D O I：

10.1182/blood-2003-02-0489

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

We studied the feasibility and activity of adding sirolimus to tacrolimus and low-dose methotrexate as graft-versus-host disease (GVHD) prophylaxis in recipients of alternative donor transplants. Forty-one patients with hematologic malignancies were conditioned with cyclophosphamide and total body irradiation. Marrow stem cells were from an HLA-A, -B, and -DR compatible, unrelated donor (n = 26, 68%), from a 5 of 6 antigen-matched unrelated donor (n = 8, 20%), or from a 5 of 6 antigen-matched family member (n = 5, 12%). Therapeutic serum levels of sirolimus were attained in most patients. All evaluable patients engrafted. An absolute neutrophil count of 500/muL was achieved on day +18 (range, 11-32 days). Sustained platelet counts of more than 20 000/ 1,L were attained on day +29 (range, 14-98 days). Grades 0-1 acute GVHD occurred in 75% of patients. Grades II, III, and IV acute GVHD occurred in 13%, 8%, and 5%, respectively (total grades II-IV GVHD, 26%). Median survival is 366 days (95% Cl 185, not estimable) and actuarial survival at 1 year is 52%. Oral sirolimus is tolerable, adequate blood levels are achievable, and there is a low rate of acute GVHD compared with historical data in this high-risk population. This novel agent is worthy of further study in allogeneic transplantation.

引用

页码：1601 / 1605

页数：5

共 41 条

[1] Interleukin-1 blockade does not prevent acute graft-versus-host disease: results of a randomized, double-blind, placebo-controlled trial of interleukin-1 receptor antagonist in allogeneic bone marrow transplantation [J].