Division of Hematology/Oncology/Cell Therapy, Rush University, Chicago, IL, USA.
CIBMTR® (Center for International Blood and Marrow Transplant Research), Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
Bone Marrow Transplant. 2024 Jan;59(1):76-84. doi: 10.1038/s41409-023-02131-z. Epub 2023 Oct 31.
Post-transplant cyclophosphamide (PTCy) is increasingly used to reduce graft-versus-host disease after hematopoietic cell transplantation (HCT); however, it might be associated with more infections. All patients who were ≥2 years old, receiving haploidentical or matched sibling donor (Sib) HCT for acute leukemias or myelodysplastic syndrome, and either calcineurin inhibitor (CNI)- or PTCy-based GVHD prophylaxis [Haploidentical HCT with PTCy (HaploCy), 757; Sibling with PTCy (SibCy), 403; Sibling with CNI-based (SibCNI), 1605] were included. Most bacterial infections occurred within the first 100 days; 953 patients (34.5%) had at least 1 infection and 352 patients (13%) had ≥2 infections. Patients receiving PTCy had a greater incidence of bacterial infections by day 180 [HaploCy 46%; SibCy 48%; SibCNI 35%; p < 0.001]. Compared with the SibCNI without infection cohort, 1.99-fold, 3.33-fold, 2.78-fold, and 2.53-fold increased TRM was seen for the HaploCy cohort without infection and HaploCy, SibCy, and SibCNI cohorts with infection, respectively. Bacterial infections increased mortality [HaploCy (HR1.84, 99% CI: 1.45-2.33, p < 0.0001), SibCy cohort (HR,1.68, 99% CI: 1.30-2.19, p < 0.0001), and SibCNI cohort (HR,1.76, 99% CI: 1.43-2.16, p < 0.0001). PTCy was associated with increased bacterial infections regardless of donor, and bacterial infections were associated with increased mortality irrespective of GVHD prophylaxis. Patients receiving PTCy should be monitored carefully for bacterial infections following PTCy.
移植后环磷酰胺(PTCy)越来越多地用于减少造血细胞移植(HCT)后的移植物抗宿主病;然而,它可能与更多的感染有关。所有年龄≥2 岁、接受单倍体或匹配同胞供体(Sib)HCT 治疗急性白血病或骨髓增生异常综合征、且接受钙调神经磷酸酶抑制剂(CNI)或 PTCy 为基础的移植物抗宿主病预防(单倍体 PTCy 组(HaploCy)757 例,同胞 PTCy 组(SibCy)403 例,同胞 CNI 组(SibCNI)1605 例)的患者均被纳入研究。大多数细菌感染发生在 100 天内;953 例(34.5%)患者至少发生 1 次感染,352 例(13%)患者发生≥2 次感染。接受 PTCy 的患者在第 180 天细菌感染发生率更高[HaploCy 组 46%;SibCy 组 48%;SibCNI 组 35%;p<0.001]。与无感染的 SibCNI 队列相比,无感染的 HaploCy 队列、HaploCy 组、SibCy 组和 SibCNI 组的感染患者的治疗相关死亡率(TRM)分别增加了 1.99 倍、3.33 倍、2.78 倍和 2.53 倍。细菌感染增加了死亡率[HaploCy 组(HR 1.84,99%CI:1.45-2.33,p<0.0001),SibCy 组(HR 1.68,99%CI:1.30-2.19,p<0.0001)和 SibCNI 组(HR 1.76,99%CI:1.43-2.16,p<0.0001)]。无论供者如何,PTCy 与细菌感染增加相关,并且无论移植物抗宿主病预防如何,细菌感染与死亡率增加相关。接受 PTCy 的患者在接受 PTCy 后应密切监测细菌感染。