Gupta Alok, Punatar Sachin, Gawande Jayant, Mathew Libin, Kannan Sadhana, Khattry Navin
Department of Medical Oncology, Bone Marrow Transplant Unit, Tata Memorial Centre, Mumbai, Maharashtra, India.
Department of Biostatistics, Advanced Centre for Treatment Research and Education in Cancer, Tata Memorial Centre, Mumbai, Maharashtra, India.
J Cancer Res Ther. 2017 Oct-Dec;13(6):981-988. doi: 10.4103/0973-1482.157338.
Trough cyclosporine (CsA) blood level can influence incidence of graft-versus-host disease (GVHD) and relapse in patients with acute leukemia undergoing allogeneic hematopoietic stem cell transplant (HSCT). We sought to determine factors affecting initial trough CsA level (CsA-1) and its impact on transplant outcome in acute leukemia.
Seventy-seven patients underwent HSCT for acute leukemia between January 2008 and March 2013 and were included. GVHD prophylaxis included CsA + methotrexate. (MTX) in 53 patients and CsA + mycophenolate mofetil (MMF) in 24 patients CsA-1 was measured on day 3-5 of starting CsA and subsequent dose was modified to achieve therapeutic level of 150-200. ng/mL. According to CsA-1, patients were divided into three groups - 27 in Group A (dose escalated), 13 in Group B (dose de-escalated), and 37 in Group C (same dose continued).
On univariate analysis, cyclophosphamide with total-body irradiation (TBI) based conditioning regimen and lower body mass index (BMI) were associated with lower CsA-1, while use of fludarabine and higher BMI were associated with higher CsA-1. On multivariate analysis, only fludarabine use and BMI affected CsA-1. Incidence of acute and chronic GVHD (aGVHD and cGVHD), transplant-related mortality, relapse incidence, and relapse-free and overall survival (OS) were similar in the three groups.
While fludarabine use in conditioning regimen and higher BMI leads to higher CsA-1, transplant outcomes are not affected by CsA-1.
环孢素（CsA）血药谷浓度可影响接受异基因造血干细胞移植（HSCT）的急性白血病患者的移植物抗宿主病（GVHD）发生率和复发情况。我们试图确定影响初始CsA谷浓度（CsA-1）的因素及其对急性白血病移植结局的影响。
纳入2008年1月至2013年3月期间接受HSCT治疗急性白血病的77例患者。移植物抗宿主病预防方案包括53例患者使用CsA+甲氨蝶呤（MTX），24例患者使用CsA+霉酚酸酯（MMF）。在开始使用CsA的第3-5天测量CsA-1，并调整后续剂量以达到150-200 ng/mL的治疗水平。根据CsA-1，患者分为三组——A组27例（剂量递增），B组13例（剂量递减），C组37例（继续相同剂量）。
单因素分析显示，基于环磷酰胺联合全身照射（TBI）的预处理方案和较低的体重指数（BMI）与较低的CsA-1相关，而使用氟达拉滨和较高的BMI与较高的CsA-1相关。多因素分析显示，只有氟达拉滨的使用和BMI影响CsA-1。三组的急性和慢性移植物抗宿主病（aGVHD和cGVHD）发生率、移植相关死亡率、复发率以及无复发生存率和总生存率（OS）相似。
虽然预处理方案中使用氟达拉滨和较高的BMI会导致较高的CsA-1，但移植结局不受CsA-1的影响。
