A phase I/II study of mycophenolate mofetil in combination with cyclosporine for prophylaxis of acute graft-versus-host disease after myeloablative conditioning and allogeneic hematopoietic cell transplantation
A phase I/II study of mycophenolate mofetil in combination with cyclosporine for prophylaxis of acute graft-versus-host disease after myeloablative conditioning and allogeneic hematopoietic cell transplantation
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DOI：
10.1016/j.bbmt.2005.03.006
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发表时间：
2005-07-01
影响因子：
4.3
通讯作者：
Storb, R
中科院分区：
文献类型：
--
作者：
Nash, RA;Johnston, L;Storb, R
在一项I/II期研究中，研究了环孢素（CSP）和霉酚酸酯（MMF）联合用于HLA匹配同胞供者的清髓性预处理和造血细胞移植后预防移植物抗宿主病（GVHD）。在第1阶段，3组（每组10例或11例患者）从第0天至第27天以每12、8和6小时递减的剂量间隔接受MMF（15 mg/kg），以确定安全有效的总日剂量。在45 mg/kg/d剂量水平下，II型患者中的4例仅发展为IT级GVHD，并且达到了与实体器官移植所述的治疗范围一致的麦考酚酸（NINIF的活性部分）的稳态浓度。在60 mg/kg/天剂量水平下，提示毒性增加，但疗效未改善。因此，选择45 mg/kg/d剂量用于11期研究，并从I期研究中将另外15例患者添加至该组（n = 26）。该剂量在第0、6、13、20和27天的稳态浓度分别为2.73、3.02、3.20、2.62和2.64 μ g/mL。在该剂量下，没有毒性归因于MMF。造血细胞移植后植入的中位时间为15天（范围，10-20天）。急性GVHD的发生率为62%，与接受CSP和甲氨蝶呤（MTX）预防GVHD的历史对照组相当。尽管与CSP和MTX相比，没有提示在预防GVHD方面有显著改善，但在MTX禁忌的病例中，可以考虑MMF联合CSP。(c)2005年美国血液和骨髓移植学会。
In a phase I/II study, the combination of cyclosporine (CSP) and mycophenolate mofetil (MMF) was investigated as graft-versus-host disease (GVHD) prophylaxis after myeloablative conditioning and hematopoietic cell transplantation from an HLA-matched sibling donor. In phase 1, 3 groups, each with 10 or I I patients, received MMF (15 mg/kg) from day 0 to day 27 at decreasing dose intervals of every 12, 8, and 6 hours to determine a safe and effective total daily dose. At the 45 mg/kg/d dosage level, 4 of I I patients developed only grade IT GVHD, and a concentration at steady state of mycophenolic acid (the active moiety of NINIF) consistent with a therapeutic range described for solid-organ transplantation was achieved. There was a suggestion of increased toxicity without improved efficacy at the 60 mg/kg/d dosage level. Accordingly, the 45 mg/kg/d dosage was therefore selected for phase 11, and another 15 patients were added to this group from the phase I study (n = 26). The concentrations at steady state for this dosage at days 0, 6, 13, 20, and 27 were 2.73, 3.02, 3.20, 2.62, and 2.64 mu g/mL, respectively. No toxicities were attributed to MMF at this dose. The median time to engraftment after hematopoietic cell transplantation was 15 days (range, 10-20 days). The incidence of acute GVHD was 62%, which was comparable to a group of historical controls receiving CSP and methotrexate (MTX) for GVHD prophylaxis. Although a significant improvement in the prevention of GVHD was not suggested, compared with CSP and MTX, MMF in combination with CSP could be considered in cases in which MTX is contraindicated. (c) 2005 American Society for Blood and Marrow Transplantotion.