A PILOT-STUDY OF LOW-DOSE CYCLOSPORINE FOR GRAFT-VERSUS-HOST PROPHYLAXIS IN MARROW TRANSPLANTATION
A PILOT-STUDY OF LOW-DOSE CYCLOSPORINE FOR GRAFT-VERSUS-HOST PROPHYLAXIS IN MARROW TRANSPLANTATION
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DOI：
10.1111/j.1365-2141.1992.tb06399.x
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发表时间：
1992-01-01
影响因子：
6.5
通讯作者：
WITHERSPOON, R
中科院分区：
文献类型：
--
作者：
STOCKSCHLAEDER, M;STORB, R;WITHERSPOON, R
19例白血病、白血病前期和再生障碍性贫血患者通过hla相同的兄弟姐妹的骨髓移植治疗。所有患者在移植后给予甲氨蝶呤（1,3,6和11天）和环孢素（-1至180天）联合免疫抑制。为了降低环孢素相关毒性，我们探讨了是否可以在前2周内将环孢素剂量减少50%（从静脉注射3.0 mg/kg/d降至1.5 mg/kg/d）而不对急性移植物抗宿主病（GVHD）的发生率、发作、严重程度和总体生存产生不利影响。该初步研究的结果与38名患者的匹配队列进行了比较，这些患者从第1天开始给予标准剂量3.0 mg环孢素/kg/d。低剂量环孢素组II级和III级急性GVHD的累积发生率为42%，而标准剂量组为51% （P = 0.60）。3年生存率分别为63%和54% （P = 0.59）。在最初14天内接受减少环孢素剂量的患者似乎具有更少的肝毒性，并且给予的甲氨蝶呤和环孢素剂量更接近每个方案的预期剂量。我们建议移植后第1天至第15天的“低剂量”环孢素可能与“标准剂量”环孢素在这段时间内预防急性GVHD一样有效。
Nineteen patients with leukaemia, preleukaemia, and aplastic anaemia were treated by marrow transplantation from HLA-identical siblings. All were given postgrafting immunosuppression with a combination of methotrexate (days 1, 3, 6 and 11) and cyclosporin (days -1 to 180). In an attempt at reducing cyclosporin-associated toxicity, we explored whether the cyclosporin dose during the first 2 weeks could be decreased by 50% (from 3.0 to 1.5 mg/kg/d intravenously) without adversely affecting the incidence, onset, and severity of acute graft-versus-host disease (GVHD) and overall survival. Results from this pilot study were compared to those of a matched cohort of 38 patients given a standard dose of 3.0 mg cyclosporin/kg/d starting on day -1. The cumulative incidence of grade II and III acute GVHD in the 'low dose' cyclosporin group was 42% compared to 51% in the 'standard dose' group (P = 0.60). Three-year survival was 63% and 54% respectively (P = 0.59). Patients receiving the reduced cyclosporin dose during the first 14 d appeared to have less hepatotoxicity, and the methotrexate and cyclosporin doses administered were closer to the doses intended per protocol. We suggest that 'low dose' cyclosporin from day -1 to day 15 postgrafting might be as effective as 'standard dose' cyclosporin during that time period for the prevention of acute GVHD.