A Randomized Phase II Trial Comparing Tacrolimus and Mycophenolate Mofetil to Tacrolimus and Methotrexate for Acute Graft-versus-Host Disease Prophylaxis
A Randomized Phase II Trial Comparing Tacrolimus and Mycophenolate Mofetil to Tacrolimus and Methotrexate for Acute Graft-versus-Host Disease Prophylaxis
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DOI：
10.1016/j.bbmt.2010.01.010
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发表时间：
2010-07-01
影响因子：
4.3
通讯作者：
Anasetti, Claudio
中科院分区：
文献类型：
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作者：
Perkins, Janelle;Field, Teresa;Anasetti, Claudio
他克莫司（Tac）加甲氨蝶呤（MTX）是预防移植物抗宿主病（GVHD）的标准方案。霉酚酸酯（MMF）有时被用来代替MTX，以尽量减少毒性，尽管缺乏对照研究证明疗效。我们进行了一项比较Tac + MMF与Tac + MTX的单中心、随机II期试验。意向治疗分析包括42例随机分配至Toe + MMF组和47例随机分配至Tac + MTX组的患者。研究组之间的患者特征无差异。Tac + MMF组患者发生重度粘膜炎、需要麻醉镇痛和肠外营养的可能性较小，并且出院时间较早。Tac + MMF组中性粒细胞恢复时间相同，但血小板恢复时间更早。100天时II-IV级急性GVHD（aGVHD）的累积发生率相似（P = .8），但Tac + MMF组中III-IV级aGVHD更高（19%对4%; P = .03）;这主要见于无关供体移植（26%对4%; P = 0.04），而在相关供体移植中更少（11%对4%; P = n.s.）。中度或重度慢性GVHD相似（P = .71）。两组在复发、非复发死亡率或总体生存率和无复发生存率方面无显著差异。霉酚酸酯的早期毒性低于甲氨蝶呤，但在预防严重aGVHD方面效果不佳，尤其是在无关供体移植中。Biol Blood Marrow Transplant 16：937-947（2010）（C）2010年美国血液和骨髓移植学会
Tacrolimus (Tac) plus methotrexate (MTX) is a standard regimen for graft-versus-host disease (GVHD) prophylaxis. Mycophenolate mofetil (MMF) is sometimes used instead of MTX to minimize toxicity, despite the lack of controlled studies demonstrating efficacy. We conducted a single-center, randomized phase II trial comparing Tac + MMF to Tac + MTX. Intent-to-treat analyses included 42 patients randomized to Toe + MMF and 47 to Tac + MTX. Patient characteristics were not different between the study arms. Patients in the Tac + MMF arm were less likely to experience severe mucositis, require narcotic analgesia and parenteral nutrition, and had earlier hospital discharge. The Tac + MMF arm had the same time to neutrophil recovery, but earlier platelet recovery. The cumulative incidence of grade II-IV acute GVHD (aGVHD) at 100 days was similar (P = .8), but grade III-IV aGVHD was higher in the Tac + MMF arm (19% versus 4%; P = .03); this was predominantly seen in unrelated donor transplants (26% versus 4%; P = .04), and less in related donor transplants (11% versus 4%; P = n.s.). Moderate or severe chronic GVHD was similar (P = .71). There were no significant differences between the arms in relapse, nonrelapse mortality, or overall and relapse-free survivals. MMF was associated with less early toxicity than MTX but was not as effective in preventing severe aGVHD, especially in unrelated donor transplants. Biol Blood Marrow Transplant 16: 937-947 (2010) (C) 2010 American Society for Blood and Marrow Transplantation