Zeighami Sara, Hadjibabaie Molouk, Ashouri Asieh, Sarayani Amir, Khoee Seyed Hamid, Mousavi Sarah, Radfar Mania, Ghavamzadeh Ardeshir
Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Department of Clinical Pharmacy, Faculty of Pharmacy, and Research Center for Rational Use of Drugs, Tehran University of Medical Sciences, Tehran, Iran.
Iran J Pharm Res. 2014 Winter;13(1):305-12.
Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment option for hematological disorders. Cyclosporine (CsA) is one of the major immunosuppressive agents for the prophylaxis against graft versus host disease (GvHD). In this retrospective study, we evaluated the effects of CsA serum levels on the incidence of acute GvHD and transplant outcomes. Retrospective study in 103 adult patients received Hematopoitic Stem Cell Transplantation (HSCT) in the Hematology-Oncology, Bone Marrow Transplantation center at Shariati Hospital in Tehran, Iran. All participants received prophylactic regimen of cyclosporine plus methotrexate. CsA dose titration was done according to patients᾽ serum levels and drug toxicity. Serum levels tested on the twice weekly basis in first 4 weeks after transplantation. Acute GvHD (grades II-IV) developed in 44 patients (43%, 95%CI: 33%-52%). The median time to ANC and PLT recovery was 13 days (range: 9-31 days) and 16 days (range: 0-38 days), respectively. Univariate analysis of risk factors related to aGvHD (grade II-IV) development showed a higher risk of incidence of aGvHD (grades II-IV) for patients having the lowest blood CSA concentration (<200 ng/mL) in the third weeks after transplantation (36% vs. 12%, P = 0.035). The only risk factors related to incidence of aGvHD grades III-IV was also blood CsA concentration at 3(rd) week post-transplant (15% vs. 3%, P = 0.047). The CsA concentration at 3(rd) week was not related to disease free survival and overall survival (P = 0.913 vs. P = 0.81) respectively. Higher CsA serum levels in the third week post HSCT significantly decreased incidence of acute GvHD.
异基因造血干细胞移植（HSCT）是治疗血液系统疾病的一种治愈性选择。环孢素（CsA）是预防移植物抗宿主病（GvHD）的主要免疫抑制剂之一。在这项回顾性研究中，我们评估了CsA血清水平对急性GvHD发生率和移植结局的影响。对伊朗德黑兰沙里亚蒂医院血液肿瘤与骨髓移植中心接受造血干细胞移植（HSCT）的103例成年患者进行回顾性研究。所有参与者均接受环孢素加甲氨蝶呤的预防方案。根据患者的血清水平和药物毒性进行CsA剂量滴定。在移植后的前4周每周检测两次血清水平。44例患者（43%，95%CI：33%-52%）发生了急性GvHD（II-IV级）。中性粒细胞计数（ANC）和血小板计数（PLT）恢复的中位时间分别为13天（范围：9-31天）和16天（范围：0-38天）。对与急性GvHD（II-IV级）发生相关的危险因素进行单因素分析显示，移植后第三周血液中CsA浓度最低（<200 ng/mL）的患者发生急性GvHD（II-IV级）的风险更高（36%对12%，P = 0.035）。与急性GvHD III-IV级发生率相关的唯一危险因素也是移植后第3周的血液CsA浓度（15%对3%，P = 0.047）。第3周的CsA浓度分别与无病生存期和总生存期无关（P = 0.913对P = 0.81）。HSCT后第三周较高的CsA血清水平显著降低了急性GvHD的发生率。
