Williams Anthony P, Bate Jessica, Brooks Rachael, Chisholm Julia, Clarke Stuart C, Dixon Elizabeth, Faust Saul N, Galanopoulou Angeliki, Heath Paul T, Maishman Thomas, Mapstone Susan, Patel Soonie R, Vora Ajay, Wilding Sam A, Gray Juliet C
Faculty of Medicine and Institute for Life Sciences University of Southampton Southampton UK.
NIHR Southampton Clinical Research Facility NIHR Southampton Biomedical Research Centre and Southampton NIHR CRUK Experimental Cancer Medicine Centre University Hospital Southampton NHS Foundation Trust Southampton UK.
EJHaem. 2020 Jun 10;1(1):142-151. doi: 10.1002/jha2.27. eCollection 2020 Jul.
Although survival rates for pediatric acute lymphoblastic leukemia are now excellent, this is at the expense of prolonged chemotherapy regimens. We report the long-term immune effects in children treated according to the UK Medical Research Council UKALL 2003 protocol. Peripheral blood lymphocyte subsets and immunoglobulin levels were studied in 116 participants, at six time points, during and for 18-month following treatment, with 30-39 patients analyzed at each time point. Total lymphocytes were reduced during maintenance chemotherapy and remained low 18 months following treatment completion. CD4 T cells remained significantly reduced 18 months after treatment, but CD8 cells and natural killer cells recovered to normal values. The fall in naïve B-cell numbers during maintenance was most marked, but numbers recovered rapidly after cessation of treatment. Memory B cells, particularly nonclass-switched memory B cells, remained below normal levels 18 months following treatment. All immunoglobulin subclasses were reduced during treatment compared to normal values, with IgM levels most affected. This study demonstrates that immune reconstitution differs between lymphocyte compartments. Although total B-cell numbers recover rapidly, disruption of memory/naïve balance persists and T-cell compartment persist at 18 months. This highlights the impact of modern chemotherapy regimens on immunity, and thus, infectious susceptibility and response to immunization.
尽管小儿急性淋巴细胞白血病的生存率目前很高，但这是以延长化疗疗程为代价的。我们报告了根据英国医学研究理事会UKALL 2003方案治疗的儿童的长期免疫效应。在治疗期间及治疗结束后的18个月内，对116名参与者在六个时间点进行外周血淋巴细胞亚群和免疫球蛋白水平的研究，每个时间点分析30 - 39名患者。在维持化疗期间总淋巴细胞减少，治疗结束后18个月仍维持在低水平。治疗后18个月CD4 T细胞仍显著减少，但CD8细胞和自然杀伤细胞恢复到正常水平。维持期幼稚B细胞数量下降最为明显，但治疗停止后数量迅速恢复。记忆B细胞，尤其是未发生类别转换的记忆B细胞，在治疗后18个月仍低于正常水平。与正常值相比，治疗期间所有免疫球蛋白亚类均减少，其中IgM水平受影响最大。本研究表明淋巴细胞各亚群的免疫重建情况不同。尽管总B细胞数量迅速恢复，但记忆/幼稚平衡的破坏持续存在，T细胞亚群在18个月时仍受影响。这突出了现代化疗方案对免疫的影响，进而影响感染易感性和免疫接种反应。
