Blood & Marrow Transplant Program, Department of Hematologic Oncology and Blood Disorders, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio.
Am J Hematol. 2015 Feb;90(2):144-8. doi: 10.1002/ajh.23882. Epub 2014 Nov 19.
Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality in allogeneic hematopoietic cell transplantation (HCT) despite current prophylaxis. Methotrexate (MTX) with a calcineurin inhibitor (CNI) is the current standard, however, has several toxicities. Mycophenolate mofetil (MMF) is frequently used in reduced-intensity HCT, but data in myeloablative transplants is limited. We thus retrospectively identified 241 patients who underwent myeloablative HCT from an HLA-identical sibling donor; 174 patients received cyclosporine (CSA) + MMF and 67 received CSA+MTX. Patients receiving MMF + CSA had rapid neutrophil (median 11 vs. 19 days with MTX+CSA), and platelet recovery (median 19 vs. 25 days), lower incidence of severe mucositis by OMAS (19% vs. 53%), and shorter length of hospital stay (median 25 vs. 36 days) (P < 0.001 for all comparisons). There were no significant differences in incidence of grade 2-4 (MMF+CSA 37% vs. MTX+CSA 39%) or 3-4 acute GVHD (17% vs. 12%), chronic GVHD (46% vs. 56%), relapse (28% vs. 27%), non-relapse mortality (20% vs. 27%), or overall survival (47% vs. 44%) (P = NS for all). However, in multivariable analysis, the use of MMF+CSA was associated with an increased risk of severe grade 3-4 acute GVHD (HR 2.92, 95% CI 1.2-7.15, P = 0.019). There were no differences between the two regimens in multivariable analyses for other survival outcomes. This analysis demonstrates that the use of MMF in myeloablative sibling donor transplantation is well tolerated. However, there may be an increased risk of severe GVHD with MMF+CSA compared to MTX+CSA. Further studies evaluating optimal dosing strategies are needed.
移植物抗宿主病（GVHD）仍然是同种异体造血细胞移植（HCT）所有患者发病和死亡的主要原因，尽管目前有预防措施。甲氨蝶呤（MTX）加钙调磷酸酶抑制剂（CNI）是目前的标准，但也有多种毒性。霉酚酸酯（MMF）常用于强度降低的 HCT，但在清髓性移植中的数据有限。因此，我们回顾性地确定了 241 例从 HLA 相同的同胞供体接受清髓性 HCT 的患者；174 例患者接受环孢菌素（CSA）+MMF，67 例患者接受 CSA+MTX。接受 MMF+CSA 的患者中性粒细胞恢复更快（中位数 11 天 vs. MTX+CSA 19 天），血小板恢复更快（中位数 19 天 vs. MTX+CSA 25 天），OMAS 严重粘膜炎发生率较低（19% vs. 53%），住院时间较短（中位数 25 天 vs. 36 天）（所有比较 P<0.001）。2-4 级（MMF+CSA 37% vs. MTX+CSA 39%）和 3-4 级急性 GVHD（17% vs. 12%）、慢性 GVHD（46% vs. 56%）、复发（28% vs. 27%）、非复发死亡率（20% vs. 27%）和总生存率（47% vs. 44%）无显著差异（所有 P=NS）。然而，多变量分析显示，使用 MMF+CSA 与严重 3-4 级急性 GVHD 的风险增加相关（HR 2.92，95%CI 1.2-7.15，P=0.019）。在多变量分析中，两种方案在其他生存结果方面没有差异。这项分析表明，在清髓性同胞供体移植中使用 MMF 是可以耐受的。然而，与 MTX+CSA 相比，MMF+CSA 可能会增加严重 GVHD 的风险。需要进一步研究评估最佳剂量策略。
