Sheth Vipul, Kennedy Vanessa, de Lavallade Hugues, Mclornan Donal, Potter Victoria, Engelhardt Brian G, Savani Bipin, Chinratanalab Wichai, Goodman Stacey, Greer John, Kassim Adetola, York Sally, Kenyon Michelle, Gandhi Shreyans, Kulasekararaj Austin, Marsh Judith, Mufti Ghulam, Pagliuca Antonio, Jagasia Madan, Raj Kavita
Department of Haematology and Stem Cell Transplantation, Kings College Hospital, London, United Kingdom.
Department of Haematology and Stem Cell Transplant, Stanford University, Stanford, CA, United States.
Front Oncol. 2019 Jul 10;9:623. doi: 10.3389/fonc.2019.00623. eCollection 2019.
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 ( = 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 ( = 0.05, HR-1.81, 1.1-3.3; = 0.002, HR-2.41, CI, 1.3-4.2; and = 0.003, HR-2.78, CI, 1.4-5.2), respectively. ALC (day 2) of 0.08 × 10/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.
用于预防移植物抗宿主病（GVHD）的抗胸腺细胞球蛋白（ATG）和抗CD52抗体（阿仑单抗）的给药方案是经验性的或基于体重的，并未考虑个体患者因素。最近研究表明，ATG给药当天受者外周血绝对淋巴细胞计数（ALC）与所给予的ATG剂量相互作用，可预测移植结果。同样，我们想分析受者ALC与阿仑单抗给药剂量是否相互作用以预测结果。我们回顾性比较了364例患者，其中124例接受ATG（抗胸腺细胞球蛋白）预防GVHD，并进行非亲缘首次异基因骨髓和淋巴瘤移植（第1组），与240例在相似时间段内接受阿仑单抗的患者（第2组）。阿仑单抗给药剂量在60至100mg之间时，生存率、急性和慢性GVHD方面没有差异。与ATG不同（移植前受者ALC在其给药当天（第1天）与ATG剂量相互作用以预测总生存期（OS）和无病生存期（DFS），P = 0.05），在阿仑单抗组中，阿仑单抗给药第二天（第2天）的受者ALC及其与阿仑单抗剂量的相互作用强烈预测OS、DFS和复发（P = 0.05，风险比[HR] - 1.81，95%置信区间[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）。第2天ALC为0.08×10⁹/L或更高在预测较差DFS方面有96%的特异性。与ATG一样，受者外周血ALC与阿仑单抗剂量之间存在明确但不同的相互作用以预测OS、DFS和复发。
