Division of Medical Oncology A, National Cancer Institute, Aviano, Italy.
Clin Infect Dis. 2010 Jun 15;50(12):1672-9. doi: 10.1086/652866.
High-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) are feasible and effective salvage treatments for human immunodeficiency virus (HIV)-related relapse or refractory lymphoma. Among the main concerns with ASCT in HIV-infected persons is the additional immune depletion caused by treatment, which could amplify the preexisting immune deficit. The aims of our study were to assess the impact of conventional chemotherapy before salvage treatment was administered, in this population, and to evaluate immune reconstitution dynamics during ASCT.
All 33 HIV-infected and HIV-uninfected patients who underwent comparable ASCT protocols at the National Cancer Institute (Aviano, Italy) who underwent 1 month of follow-up after transplantation were included in a prospective immunological study. Demographic, clinical, and immunovirological data were obtained before administration of induction therapy, during transplantation, and at 24 months of follow-up.
Before HDC, no significant differences were observed in CD4(+) cell subsets and signal joint T cell receptor excision circles (sjTRECs), although HIV-infected persons had inverted ratios of CD4(+) cells to CD8(+) cells because they had higher CD8(+) T cell counts, compared with HIV-uninfected persons. After ASCT, this inversion was also observed in HIV-uninfected patients up to 24 months. CD4(+) cell subsets had similar recoveries, with a temporary setback in HIV-infected persons 3 months after reinfusion, together with an increase in infections. sjTRECs demonstrated similar dynamics in both populations and serve as a useful predictive marker of recovery of CD4(+) cell subsets. No significant changes emerged in HIV DNA levels during the follow-up period, with values at 24 months significantly lower than those at baseline.
Our study demonstrated that ASCT in HIV-infected persons with lymphoma does not worsen the initial immune impairment and does not enhance viral replication or the peripheral HIV reservoir in the long term.
高剂量化疗(HDC)和自体干细胞移植(ASCT)是治疗人类免疫缺陷病毒(HIV)相关复发或难治性淋巴瘤的可行且有效的挽救治疗方法。在 HIV 感染者中进行 ASCT 的主要关注点之一是治疗引起的额外免疫耗竭,这可能会放大先前存在的免疫缺陷。我们的研究目的是评估在进行挽救治疗之前,常规化疗对该人群的影响,并评估 ASCT 期间免疫重建的动态。
所有在意大利国家癌症研究所(阿维亚诺)接受可比 ASCT 方案且在移植后接受 1 个月随访的 33 名 HIV 感染和 HIV 未感染的患者均纳入前瞻性免疫研究。在诱导治疗前、移植期间和 24 个月随访时获得人口统计学、临床和免疫病毒学数据。
在 HDC 之前,CD4+细胞亚群和信号接头 T 细胞受体切除环(sjTRECs)没有明显差异,尽管 HIV 感染者的 CD4+细胞与 CD8+细胞的比例倒置,因为他们的 CD8+T 细胞计数较高,与 HIV 未感染的人相比。在 ASCT 后,这种倒置也在 HIV 未感染的患者中观察到,直到 24 个月。CD4+细胞亚群的恢复相似,在再输注后 3 个月 HIV 感染者的恢复出现暂时倒退,同时感染增加。两种人群的 sjTRECs 表现出相似的动态,是 CD4+细胞亚群恢复的有用预测标志物。在随访期间,HIV DNA 水平没有出现明显变化,24 个月时的值明显低于基线。
我们的研究表明,淋巴瘤合并 HIV 感染者的 ASCT 不会加重初始免疫损害,也不会长期增强病毒复制或外周 HIV 储存库。