Marchesi F, Pimpinelli F, Dessanti M L, Gumenyuk S, Palombi F, Pisani F, Romano A, Spadea A, Maschio M, Ensoli F, Mengarelli A
Hematology and Stem Cell Transplantation Unit, Regina Elena National Cancer Institute, Rome, Italy.
Transpl Infect Dis. 2014 Dec;16(6):1032-8. doi: 10.1111/tid.12309. Epub 2014 Nov 5.
The introduction of proteasome inhibitors and/or immunomodulators in the treatment of myeloma has led to an increase in viral infections, particularly in the Herpesviridae family. Previous studies about the risk of cytomegalovirus (CMV) reactivation after autologous stem cell transplantation (ASCT) have examined the clinical outcome after the first ASCT; however, only 1 study to date has investigated the risk of CMV reactivation after a second transplantation. To address this issue, we performed a retrospective chart review on 78 consecutive myeloma patients (median age 56 years) who underwent a tandem non-CD34(+) selected ASCT after induction treatment with either conventional chemotherapy (n = 42) or with novel agents (n = 36), respectively. All subjects had been mobilized and conditioned with cyclophosphamide plus granulocyte colony-stimulating factor and melphalan alone, respectively. CMV DNA load in the blood has been determined by polymerase chain reaction in the case of a clinical suspicion of CMV reactivation; therefore, routine monitoring was not performed. Considering the outcome of both the first and the second transplantations, we observed a total of 13 episodes of symptomatic CMV reactivation (13/156, 8%), in 12 subjects (12/78, 15%), all successfully treated. Eight subjects experienced a CMV reactivation after the first ASCT (8/78, 10%); however, only 1 of them (1/8, 12%) experienced a CMV reactivation after the second transplantation. Conversely, 4 CMV reactivations (6%) were observed after the second transplantation in the group of 70 patients who did not experience a CMV reactivation after the first ASCT. No statistically significant difference was observed between first and second ASCT (8/78, 10% vs. 5/78, 6%; P = 0.767). Univariate analysis showed that a pre-transplant treatment with novel agents was the only baseline factor significantly associated with the occurrence of post-ASCT CMV symptomatic reactivation after the first transplant (odds ratio [OR]: 9.897; 95% confidence interval [CI]: 1.154-84.840; P = 0.021) but not after the second transplant (OR: 5.125; 95% CI: 0.546-48.119; P = 0.115). No end-organ disease or primary infection was documented. Our data suggest that second transplantation does not increase the risk of CMV reactivation in our patient population, when compared with the first one, and confirm the role of a pre-transplant treatment with novel agents as a risk factor for CMV symptomatic reactivation.
蛋白酶体抑制剂和/或免疫调节剂用于骨髓瘤治疗后，病毒感染有所增加，尤其是疱疹病毒科感染。以往关于自体干细胞移植（ASCT）后巨细胞病毒（CMV）再激活风险的研究，考察的是首次ASCT后的临床结局；然而，迄今为止仅有1项研究调查了二次移植后CMV再激活的风险。为解决这一问题，我们对78例连续的骨髓瘤患者（中位年龄56岁）进行了回顾性病历审查，这些患者在分别接受传统化疗（n = 42）或新型药物（n = 36）诱导治疗后，进行了非CD34(+)选择的串联ASCT。所有受试者分别采用环磷酰胺加粒细胞集落刺激因子和单用美法仑进行动员和预处理。在临床怀疑CMV再激活时，通过聚合酶链反应测定血液中的CMV DNA载量；因此，未进行常规监测。考虑到首次和二次移植的结局，我们共观察到13例有症状的CMV再激活事件（13/156，8%），涉及12名受试者（12/78，15%），均成功治疗。8名受试者在首次ASCT后出现CMV再激活（8/78，10%）；然而，其中只有1人（1/8，12%）在二次移植后出现CMV再激活。相反，在首次ASCT后未出现CMV再激活的70例患者组中，有4例（6%）在二次移植后出现CMV再激活。首次和二次ASCT之间未观察到统计学显著差异（8/78，10%对5/78，6%；P = 0.767）。单因素分析显示，移植前使用新型药物治疗是首次移植后ASCT后CMV有症状再激活发生的唯一显著相关基线因素（比值比[OR]：9.897；95%置信区间[CI]：1.154 - 84.840；P = 0.021），但二次移植后并非如此（OR：5.125；95% CI：0.546 - 48.119；P = 0.115）。未记录到终末器官疾病或原发性感染。我们的数据表明，与首次移植相比，二次移植在我们的患者群体中不会增加CMV再激活的风险，并证实了移植前使用新型药物治疗作为CMV有症状再激活风险因素的作用。
