Division of Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts; Stem Cell Transplant and Cellular Therapy, Dana-Farber Cancer Institute, Boston, Massachusetts.
Stem Cell Transplant and Cellular Therapy, Dana-Farber Cancer Institute, Boston, Massachusetts; Sorbonne University, Department of Clinical Hematology and Cellular Therapy, Saint-Antoine Hospital, Assistance Publique-Hôpitaux de Paris, Inserm UMRs 938, Centre de recherche Saint-Antoine, Paris, France.
Transplant Cell Ther. 2024 Feb;30(2):233.e1-233.e14. doi: 10.1016/j.jtct.2023.11.015. Epub 2023 Nov 18.
Post-transplantation cyclophosphamide (PTCy) is an effective strategy for graft-versus-host disease (GVHD) prophylaxis and is the standard of care for haploidentical hematopoietic cell transplantation (HCT). It is increasingly used for matched and mismatched unrelated donor (MUD/MMUD) HCT, but infections remain a concern. The objective of this study was to evaluate the characteristics and risk factors for infections in haploidentical and unrelated donor HCT recipients treated with PTCy-based GVHD prophylaxis. This single-center retrospective study examined 354 consecutive adults undergoing HCT with PTCy-based GVHD prophylaxis (161 MUD/MMUD; 193 haploidentical) between 2015 and 2022. Opportunistic infections (OIs), including cytomegalovirus (CMV), adenovirus (AdV), Epstein-Barr virus (EBV), and invasive fungal disease (IFD), were assessed from day 0 through day +365. The 1-year cumulative incidence functions of OIs and nonrelapse mortality (NRM) were calculated using dates of relapse and repeat HCT as competing risks. Secondary analysis evaluated risk factors for OIs and NRM using univariate and multivariable Cox regression models. Haploidentical HCT recipients had an increased risk of OIs compared to unrelated donor allograft recipients (39% for haploidentical versus 25% for MUD/MMUD; hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.16 to 2.49; P = .006). On multivariable analysis, haploidentical donor (HR, 1.50; 95% CI, 1.01 to 2.23; P = .046), prior HCT (HR, 1.99; 95% CI, 1.29 to 3.09; P = .002), and diagnosis of aGVHD (HR, 1.47; 95% CI, 1.02 to 2.14; P = .041) were associated with increased risk of OIs. NRM within the first year was not significantly different between the 2 cohorts (HR, 1.11; 95% CI, .64 to 1.93; P = .70). Overall, haploidentical donor was a significant risk factor for OIs in patients receiving PTCy, although 1-year NRM was not different between haploidentical HCT and MUD/MMUD HCT recipients. CMV and AdV infections were significantly increased among haploidentical HCT recipients, whereas the incidences of EBV infection and IFD were similar in the 2 cohorts. Our findings may have implications for infection monitoring and prophylaxis in the setting of PTCy, particularly in haploidentical HCT recipients.
移植后环磷酰胺（PTCy）是预防移植物抗宿主病（GVHD）的有效策略，也是单倍体造血细胞移植（HCT）的标准治疗方法。它越来越多地用于匹配和不匹配的无关供体（MUD/MMUD）HCT，但感染仍然是一个问题。本研究的目的是评估接受 PTCy 为基础的 GVHD 预防治疗的单倍体和无关供体 HCT 受者感染的特征和危险因素。这项单中心回顾性研究评估了 2015 年至 2022 年间 354 例连续接受 PTCy 为基础的 GVHD 预防治疗的成人 HCT 患者（161 例 MUD/MMUD；193 例单倍体）。从第 0 天到第+365 天评估机会性感染（OIs），包括巨细胞病毒（CMV）、腺病毒（AdV）、EB 病毒（EBV）和侵袭性真菌病（IFD）。使用复发和重复 HCT 的日期作为竞争风险，计算 OIs 和非复发死亡率（NRM）的 1 年累积发生率函数。使用单变量和多变量 Cox 回归模型对 OIs 和 NRM 的危险因素进行二次分析。与无关供体同种异体移植物受者相比，单倍体 HCT 受者 OIs 的风险增加（单倍体 39%，MUD/MMUD 25%；风险比[HR]，1.70；95%置信区间[CI]，1.16 至 2.49；P=.006）。多变量分析显示，单倍体供体（HR，1.50；95%CI，1.01 至 2.23；P=.046）、先前的 HCT（HR，1.99；95%CI，1.29 至 3.09；P=.002）和急性移植物抗宿主病（aGVHD）的诊断（HR，1.47；95%CI，1.02 至 2.14；P=.041）与 OIs 的风险增加相关。两组第 1 年的 NRM 无显著差异（HR，1.11；95%CI，.64 至 1.93；P=.70）。总体而言，单倍体供体是接受 PTCy 治疗的患者发生 OIs 的显著危险因素，尽管单倍体 HCT 和 MUD/MMUD HCT 受者的 1 年 NRM 无差异。单倍体 HCT 受者的 CMV 和 AdV 感染明显增加，而两组 EBV 感染和 IFD 的发生率相似。我们的研究结果可能对 PTCy 背景下的感染监测和预防具有重要意义，特别是在单倍体 HCT 受者中。
