Table_1_Differential Interaction of Peripheral Blood Lymphocyte Counts (ALC) With Different in vivo Depletion Strategies in Predicting Outcomes of Allogeneic Transplant: An International 2 Center Experience.docx

Dosing regimens for antithymocyte globulin (ATG) and anti-CD52 antibody (alemtuzumab) for graft vs. host disease prophylaxis (GVHD) are empiric or weight-based, and do not account for individual patient factors. Recently, it has been shown that recipient peripheral blood absolute lymphocyte count (ALC) on the day of ATG administration interacts with the dose of ATG administered to predict transplantation outcome. Similarly, we wanted to analyze if the recipient ALC interacts with alemtuzumab dosing to predict outcomes. We retrospectively compared 364 patients, 124 patients receiving ATG (anti-thymocyte globulin) for GVHD prophylaxis, and undergoing unrelated first allogeneic transplant for myeloid and lymphoid malignancies (group 1) to 240 patients receiving alemtuzumab (group 2), in similar time period. There was no difference in survival or acute and chronic GVHD between 60 and 100 mg of alemtuzumab dosing. Unlike ATG (where the pre-transplant recipient ALC interacted with ATG dose on day of its administration (day 1) to predict OS and DFS (p = 0.05), within alemtuzumab group, the recipient ALC on second day of alemtuzumab administration (day 2) and its interaction with alemtuzumab dose strongly predicted OS, DFS and relapse (p = 0.05, HR-1.81, 1.1–3.3; p = 0.002, HR-2.41, CI, 1.3–4.2; and p = 0.003, HR-2.78, CI, 1.4–5.2), respectively. ALC (day 2) of 0.08 × 109/lit or higher, had a specificity of 96% in predicting inferior DFS. Like ATG, there is definite but differential interaction between the recipient peripheral blood ALC and alemtuzumab dose to predict OS, DFS, and relapses.

用于移植物抗宿主病（graft vs. host disease, GVHD）预防的抗胸腺细胞球蛋白（antithymocyte globulin, ATG）与抗CD52单克隆抗体（alemtuzumab, 阿仑单抗）的给药方案多为经验性方案或基于体重的方案，未纳入患者个体差异因素。近期研究表明，在给予抗胸腺细胞球蛋白当日，受者外周血绝对淋巴细胞计数（absolute lymphocyte count, ALC）与ATG给药剂量存在交互作用，可用于预测移植结局。与此类似，本研究旨在探讨受者ALC与阿仑单抗给药剂量的交互作用是否可用于预测移植结局。本研究回顾性对比分析了364例患者：其中124例接受ATG用于GVHD预防，因髓系与淋巴系恶性肿瘤接受首次非亲缘异基因造血干细胞移植（队列1）；剩余240例接受阿仑单抗治疗（队列2），两组患者的入组时间区间相近。阿仑单抗给药剂量处于60mg至100mg区间时，患者的总生存期、急性与慢性GVHD发生率均无统计学差异。与ATG不同的是，ATG给药当日（第1日）受者的移植前外周血ALC与ATG剂量的交互作用可预测总生存期（overall survival, OS）与无病生存期（disease-free survival, DFS，p=0.05）；而在阿仑单抗队列中，受者在阿仑单抗给药第2日的ALC水平及其与阿仑单抗剂量的交互作用可显著预测OS、DFS与复发风险（分别为p=0.05，风险比（hazard ratio, HR）=1.81，置信区间（confidence interval, CI）：1.1~3.3；p=0.002，HR=2.41，CI：1.3~4.2；p=0.003，HR=2.78，CI：1.4~5.2）。当受者第2日ALC≥0.08×10^9/L时，其预测不良DFS的特异性可达96%。与ATG的研究结果一致，受者外周血ALC与阿仑单抗给药剂量之间存在明确但存在差异的交互作用，可用于预测OS、DFS与复发风险。