Comparison of Tacrolimus and Sirolimus (Tac/Sir) versus Tacrolimus, Sirolimus, and Mini-Methotrexate (Tac/Sir/MTX) as Acute Graft-versus-Host Disease Prophylaxis after Reduced-Intensity Conditioning Allogeneic Peripheral Blood Stem Cell Transplantation
Comparison of Tacrolimus and Sirolimus (Tac/Sir) versus Tacrolimus, Sirolimus, and Mini-Methotrexate (Tac/Sir/MTX) as Acute Graft-versus-Host Disease Prophylaxis after Reduced-Intensity Conditioning Allogeneic Peripheral Blood Stem Cell Transplantation
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DOI：
10.1016/j.bbmt.2009.03.017
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发表时间：
2009-07-01
影响因子：
4.3
通讯作者：
Alyea, Edwin P.
中科院分区：
文献类型：
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作者：
Ho, Vincent T.;Aldridge, Julie;Alyea, Edwin P.
先前的研究表明，在他克莫司/微量甲氨蝶呤方案（Tac/Sir/MTX）中加入西罗莫司作为移植物抗宿主病（GVHD）预防剂，可降低强度预处理（RIC）异基因干细胞移植（SCT）后急性GVHD（aGVHD）的发生率。为了评估移植后甲氨蝶呤MTX是否可以安全地完全消除，我们进行了一项前瞻性临床试验，测试T和Sir单独（tac/sir）的组合作为GVHD预防RIC SCT后匹配的相关供体。我们将结果与既往前瞻性研究中接受（Tac/Sir/MTX）作为RIC SCT后GVHD预防的患者进行了比较。两组患者在第-5天至第-2天接受静脉注射氟达拉滨（Flu）30 mg/m2/天和静脉注射白消安（Bu）0.8 mg/kg/天作为预处理，随后移植未经操作的非格司亭动员的外周血干细胞（PBSCS）。移植后，两组患者从第-3天开始口服Tac和Sir，调整剂量以分别达到5至10 ng/mL和3至12 ng/mL的血清谷水平。Tac/Sir/MTX组在常规化疗基础上加用微量MTX（5 mg/m2，iv.）在第+1、+3和+6天。非格司亭5 μ g/kg/天s.c.在第+ I天开始，并持续至中性粒细胞植入。29例患者接受Tac/Sir方案，46例患者接受Tac/Sir/MTX方案。两组在年龄、性别和疾病特征方面均衡。两组移植物植入活跃，移植后供体嵌合体稳定。两组中II-IV级aGVHD的累积发生率相似（Tac/Sir组为17%，Tac/Sir/MTX组为11%; P = 0.46）。两组在广泛慢性GVHD（cGVHD）累积发生率、治疗相关死亡率（TRM）、疾病复发或生存率方面也无差异。用于GVHD预防的Tac/Sir组合耐受性良好，并且与匹配的相关供体RIC SCT中aGVHD的低发生率相关。从Tac/Sir GVHD预防方案中省略mini-MTX似乎对aGVHD的发展没有不利影响。
Previous studies have shown that adding sirolimus to a tacrolimus/mini-methotrexate regimen (Tac/Sir/MTX) as graft-versus-host disease (GVHD) prophylaxis produces low rates of acute GVHD (aGVHD) after reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (SCT). To assess whether posttransplantation methotrexate MTX can be safely eliminated altogether, we conducted a prospective clinical trial testing the combination of T and Sir alone (tac/sir) as GVHD prophylaxis after RIC SCT from matched related donors. We compared the results with patients who received (Tac/Sir/MTX) as GVHD prophylaxis after RIC SCT from matched related donors in a previous prospective study. Patients in both groups received i.v. fludarabine (Flu) 30 mg/m(2)/day and i.v. busulfan (Bu) 0.8 mg/kg/day on days -5 to -2 as conditioning, followed by transplantation of unmanipulated filgrastim-mobilized peripheral blood stem cells (PBSCS). After transplantation, patients in both groups received Tac and Sir orally starting on day -3, with doses adjusted to achieve trough serum levels of 5 to 10 ng/mL and 3 to 12 ng/mL, respectively. The patients in the Tac/Sir/MTX group also received mini-MTX therapy (S mg/m(2) i.v.) on days + 1, + 3, and + 6. Filgrastim 5 mu g/kg/day s.c. was started on day + I and continued until neutrophil engraftment. Twenty-nine patients received the Tac/Sir regimen, and 46 patients received the Tac/Sir/MTX regimen. The 2 groups were balanced in terms of age, sex, and disease characteristics. Engraftment was brisk and donor chimerism after transplantation robust in both groups. The cumulative incidence of grade II-IV aGVHD was similar in the 2 groups (17% for Tac/Sir versus 11% for Tac/Sir/MTX; P = .46). There also were no differences between the 2 groups in cumulative incidence of extensive chronic GVHD (cGVHD), treatment-related mortality (TRM), disease relapse, or survival. The Tac/Sir combination for GVHD prophylaxis is well tolerated and associated with a low incidence of aGVHD in matched related donor RIC SCT The omission of mini-MTX from the Tac/Sir GVHD prophylaxis regimen appears to have no adverse effect on the development of aGVHD.