Hematology and Stem Cell Transplant Unit, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi, 53 00144 Rome, Italy.
Molecular Virology, Pathology and Microbiology, IRCCS San Gallicano Dermatological Institute, Via Elio Chianesi, 53 00144 Rome, Italy.
Int J Mol Sci. 2019 Mar 19;20(6):1373. doi: 10.3390/ijms20061373.
Unlike allogeneic transplant, autologous stem cell transplantation (ASCT) represents a procedure with a low-risk of cytomegalovirus (CMV) symptomatic reactivation-infection/end-organ disease (CMV complications) and invasive fungal disease (IFD). However, novel drugs for the treatment of lymphoproliferative malignancies could cause an increase of such opportunistic infections, even after ASCT. To the best of our knowledge, there are no published data demonstrating an association between CMV and IFD in the autologous setting, while this association has been widely reported in allogeneic transplantation. We have reviewed our series of 347 ASCT in myeloma and lymphoma patients performed over a period of 14 years with the aim of investigating the descriptive and analytical epidemiology of bacterial, CMV and IFD complications, focusing on the association between CMV and IFD. Patients with myeloma have significantly fewer bacterial infections and IFD than patients with lymphoma, but a similar rate of CMV complications. Descriptive epidemiological data are consistent with the literature, indicating an overall incidence of 36%, 3.5% and 15.5% for bacterial infections, IFD and CMV complications, with a case mortality rate of 4%, 16.7% and 3.7%, respectively. A strong correlation between CMV and IFD exists, with 8 cases of IFD out of a total of 12 presenting a CMV complication. At multivariate analysis, a diagnosis of lymphoma, ≥3 previous treatment lines and age ≥60 years were found to be independent risk factors for IFD. Duration of neutropenia (ANC < 500/mm³) ≥7 days represents an independent risk factor for CMV complications, where neutropenia most likely represents a crude surrogate biomarker indicating a deeper and longer state of overall immunosuppression. From our data we conclude that (1) myeloma patients are at lower risk of bacterial infections and IFD as compared with lymphoma patients but are at equal risk of CMV complications, most likely as a consequence of a selective impact of bortezomib on Herpes Viruses infection control; (2) a significant association exists between CMV and IFD, although a possible cause-effect relationship remains to be determined; (3) IFD is a rare complication after ASCT but burdened by a mortality rate of about 17%, with peak rates in older lymphoma patients who underwent more intensive therapeutic regimens.
与异基因移植不同，自体造血干细胞移植（ASCT）发生巨细胞病毒（CMV）症状性再激活/感染/靶器官疾病（CMV 并发症）和侵袭性真菌病（IFD）的风险较低。然而，新型治疗淋巴增殖性恶性肿瘤的药物可能会导致这些机会性感染增加，即使在 ASCT 后也是如此。据我们所知，在自体造血干细胞移植中，尚无关于 CMV 与 IFD 之间关联的发表数据，而在异基因移植中，这种关联已被广泛报道。我们回顾了我们在 14 年期间对 347 例多发性骨髓瘤和淋巴瘤患者进行的 ASCT 系列，旨在研究细菌、CMV 和 IFD 并发症的描述性和分析流行病学，重点关注 CMV 和 IFD 之间的关联。与淋巴瘤患者相比，骨髓瘤患者的细菌感染和 IFD 明显较少，但 CMV 并发症的发生率相似。描述性流行病学数据与文献一致，表明细菌感染、IFD 和 CMV 并发症的总体发生率分别为 36%、3.5%和 15.5%，病例死亡率分别为 4%、16.7%和 3.7%。CMV 和 IFD 之间存在很强的相关性，在总共 12 例 IFD 中有 8 例存在 CMV 并发症。多变量分析发现，淋巴瘤诊断、≥3 线既往治疗和年龄≥60 岁是 IFD 的独立危险因素。中性粒细胞减少症持续时间（ANC＜500/mm³）≥7 天是 CMV 并发症的独立危险因素，中性粒细胞减少症很可能是总体免疫抑制程度更深、时间更长的粗略替代生物标志物。根据我们的数据，我们得出以下结论：（1）与淋巴瘤患者相比，骨髓瘤患者发生细菌感染和 IFD 的风险较低，但发生 CMV 并发症的风险相同，这很可能是硼替佐米对疱疹病毒感染控制的选择性影响所致；（2）CMV 和 IFD 之间存在显著关联，尽管因果关系仍有待确定；（3）ASCT 后 IFD 是一种罕见的并发症，但死亡率约为 17%，在接受更强化治疗方案的老年淋巴瘤患者中发病率更高。
