Willemsen Laura, Jol-van der Zijde Cornelia M, Admiraal Rick, Putter Hein, Jansen-Hoogendijk Anja M, Ostaijen-Ten Dam Monique M, Wijnen Juul T, van Kesteren Charlotte, Waaijer Jacqueline L M, Lankester Arjan C, Bredius Robbert G M, van Tol Maarten J D
Pediatric SCT Unit and Laboratory for Immunology, Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
Pediatric SCT Unit and Laboratory for Immunology, Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
Biol Blood Marrow Transplant. 2015 Mar;21(3):473-82. doi: 10.1016/j.bbmt.2014.11.674. Epub 2014 Dec 5.
The outcome of allogeneic hematopoietic stem cell transplantation (HSCT) is strongly affected by the kinetics of reconstitution of the immune system. This study compared the effects of antithymocyte globulin (ATG) and alemtuzumab on various outcome parameters after HSCT. The study cohort consisted of 148 children, with a median age of 9.6 years (range, .4 to 19.0), who underwent HSCT for malignant and benign hematological disorders in a single HSCT unit. Conditioning included ATG (n = 110) or alemtuzumab (n = 38). Cox proportional hazard regression analysis showed that alemtuzumab significantly delayed the recovery of CD3(+) T cells and CD4(+)as well as CD8(+) T cell subsets (P ≤ .001) and natural killer (NK) cells (P = .008) compared with ATG. In both ATG- and alemtuzumab-treated patients, shorter drug exposure lead to significantly faster recovery of T cells. Alemtuzumab was associated with lower donor chimerism 3 and 6 months after transplantation and a higher risk of disease relapse (P = .001). The overall survival and event-free survival risks were significantly lower for alemtuzumab-treated patients (P = .020 and P < .001, respectively). Patients who received alemtuzumab showed a trend to lower risk of acute graft-versus-host disease, more human adenovirus, and less Epstein-Barr virus reactivations compared with patients who received ATG. These data indicate that children treated with alemtuzumab as part of the conditioning regimen have a slower T cell and NK cell reconstitution compared with those treated with ATG, which compromises the overall and event-free survival. Prolonged length of lympholytic drug exposure delayed the T cell recovery in both ATG- and alemtuzumab-treated patients. Therefore, we recommend detailed pharmacokinetic/pharmacodynamic (PK/PD) analyses in a larger cohort of patients to develop an algorithm aiming at optimization of the serotherapy containing conditioning regimen.
异基因造血干细胞移植（HSCT）的结果受到免疫系统重建动力学的强烈影响。本研究比较了抗胸腺细胞球蛋白（ATG）和阿仑单抗对HSCT后各种结果参数的影响。研究队列包括148名儿童，中位年龄为9.6岁（范围为0.4至19.0岁），他们在单个HSCT单位接受了针对恶性和良性血液系统疾病的HSCT。预处理方案包括使用ATG（n = 110）或阿仑单抗（n = 38）。Cox比例风险回归分析表明，与ATG相比，阿仑单抗显著延迟了CD3(+) T细胞、CD4(+)以及CD8(+) T细胞亚群（P≤0.001）和自然杀伤（NK）细胞（P = 0.008）的恢复。在接受ATG和阿仑单抗治疗的患者中，较短的药物暴露时间导致T细胞恢复明显更快。阿仑单抗与移植后3个月和6个月时较低的供体嵌合率以及较高的疾病复发风险相关（P = 0.001）。接受阿仑单抗治疗的患者的总生存风险和无事件生存风险显著更低（分别为P = 0.020和P < 0.001）。与接受ATG的患者相比，接受阿仑单抗的患者显示出急性移植物抗宿主病风险较低、人腺病毒感染较多以及爱泼斯坦 - 巴尔病毒再激活较少的趋势。这些数据表明，与接受ATG治疗的儿童相比，接受阿仑单抗作为预处理方案一部分治疗的儿童T细胞和NK细胞重建较慢，这会影响总生存和无事件生存。在接受ATG和阿仑单抗治疗的患者中，延长淋巴细胞溶解药物暴露时间会延迟T细胞恢复。因此，我们建议在更大的患者队列中进行详细的药代动力学/药效学（PK/PD）分析，以制定旨在优化包含预处理方案的血清疗法的算法。
Zotero 插件