Sirolimus, tacrolimus, and low-dose methotrexate for graft-versus-host disease prophylaxis in mismatched related donor or unrelated donor transplantation
Sirolimus, tacrolimus, and low-dose methotrexate for graft-versus-host disease prophylaxis in mismatched related donor or unrelated donor transplantation
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DOI：
10.1182/blood-2003-02-0489
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发表时间：
2003-09-01
期刊：
影响因子：
20.3
通讯作者：
Soiffer, RJ
中科院分区：
文献类型：
--
作者：
Antin, JH;Kim, HT;Soiffer, RJ
我们研究了西罗莫司加入他克莫司和低剂量甲氨蝶呤作为替代供体移植受者移植物抗宿主病（GVHD）预防的可行性和活性。41例恶性血液病患者接受环磷酰胺和全身照射。骨髓干细胞来自HLA-A、-B和-DR相容的无亲缘关系供者（n = 26, 68%），来自抗原匹配的无亲缘关系供者（n = 8, 20%），或来自抗原匹配的家族成员（n = 5, 12%）。大多数患者的西罗莫司达到治疗血清水平。所有可评估的患者都进行了移植。在第18天（范围，11-32天）中性粒细胞绝对计数达到500/muL。在第29天（14-98天），持续血小板计数超过20000 / 1l。75%的患者发生0-1级急性GVHD。II级、III级和IV级急性GVHD发生率分别为13%、8%和5% （II-IV级GVHD总发生率为26%）。中位生存期为366天（95% Cl 185，不可估计），1年精算生存率为52%。口服西罗莫司可耐受，可达到足够的血药浓度，与历史数据相比，该高危人群的急性GVHD发生率较低。这种新型药物在同种异体移植中值得进一步研究。
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.