Przepiorka D, Shapiro S, Schwinghammer T L, Bloom E J, Rosenfeld C S, Shadduck R K, Venkataramanan R
Pittsburgh Cancer Institute, Adult Bone Marrow Transplant Unit, Montefiore Hospital.
Bone Marrow Transplant. 1991 Jun;7(6):461-5.
A combination of cyclosporine (CSA) and methylprednisolone (MP) was used as graft-versus-host disease (GVHD) prophylaxis in 25 patients age 11-47 years (median 27 years) who received HLA-compatible sibling marrow transplants after myeloablative therapy for leukemia, myelodysplasia or lymphoma. CSA was initiated at 3 mg/kg/day in two divided doses, and the dose was adjusted to maintain a trough whole blood h.p.l.c. concentration between 200 and 800 ng/ml. While on i.v. CSA, the dose of CSA was increased for 10 of the 25 patients. The actuarial rate of grades II-IV acute GVHD was 37%. Those patients who developed moderate to severe GVHD had a significantly higher early mortality than those who did not (56% vs 12%, p = 0.02). There was a significant association between the development of acute GVHD and a mean week 2 CSA trough concentration less than 250 ng/ml. Life threatening regimen-related toxicities in the first 100 days included capillary leak syndrome, acute pancreatitis and small bowel perforation. Although the combination of CSA and MP in this dosing schedule was active in preventing acute GVHD, nephrotoxicity remained a problem, and outcome was limited by the inability to achieve the target CSA trough concentration in a substantial proportion of patients.
25例年龄在11至47岁（中位数27岁）的患者，在接受白血病、骨髓增生异常综合征或淋巴瘤的清髓性治疗后，接受了HLA相合同胞骨髓移植，使用环孢素（CSA）和甲泼尼龙（MP）联合方案预防移植物抗宿主病（GVHD）。CSA起始剂量为3mg/kg/天，分两次给药，剂量根据全血高效液相色谱法（h.p.l.c.）谷浓度维持在200至800ng/ml进行调整。在静脉输注CSA期间，25例患者中有10例增加了CSA剂量。II-IV级急性GVHD的实际发生率为37%。发生中度至重度GVHD的患者早期死亡率显著高于未发生者（56%对12%，p=0.02）。急性GVHD的发生与第2周CSA平均谷浓度低于250ng/ml之间存在显著关联。100天内危及生命的与治疗方案相关的毒性包括毛细血管渗漏综合征、急性胰腺炎和小肠穿孔。尽管该给药方案中的CSA和MP联合方案在预防急性GVHD方面有效，但肾毒性仍然是一个问题，且由于相当一部分患者无法达到目标CSA谷浓度，治疗效果受到限制。
