Clinic of Infectious Diseases, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Biol Blood Marrow Transplant. 2020 Jun;26(6):1179-1188. doi: 10.1016/j.bbmt.2020.01.013. Epub 2020 Jan 28.
Incidence and outcome of infections after allogeneic hematopoietic stem cell transplantation (HSCT) with post-transplant cyclophosphamide (PT-Cy) as graft-versus-host disease (GVHD) prophylaxis are largely unknown. Study aims were to estimate the incidence of pre-engraftment bloodstream infections (PE-BSIs) and viral infections (VIs; cytomegalovirus [CMV], adenovirus [ADV], human herpes virus 6 [HHV6], and BK-polyomavirus hemorrhagic-cystitis [BKPyV-HC]), their predictive factors, and infection-related mortality (IRM) after HSCT with PT-Cy. We analyzed 235 patients: 62%, 21%, and 17% received haploidentical (haplo), matched-unrelated donor (MUD), and matched-related donor, respectively. Overall, 72 patients had 77 PE-BSI episodes at a median time of 13 days after HSCT: cumulative incidence function (CIF) at 28 days was 32%, without differences among donor types (P = .988). By multivariate analysis, CIF of PE-BSI was higher in patients with severe neutropenia before HSCT (adjusted hazard ratio [AHR] = 2.90) and in multidrug-resistant Gram-negative bacteria rectal carriers (AHR = 2.68). IRM at 30 days was 5%, without differences by donor type (P = .106). Overall, 208 patients experienced ≥1 VIs (first occurrence among CMV, HHV6, ADV, BKPyV-HC) at a median time of 20 days after HSCT: CIF at 90 days was 91%, significantly higher in MUD and haplo (P = .0089). By multivariate analysis, also acute GVHD grade ≥2 (AHR = 1.32) and host/donor CMV-serology mismatch (positive/positive versus negative/negative: AHR = 2.95, positive/negative versus negative/negative: AHR = 2.41, negative/positive versus negative/negative: AHR = 2.35) affected VIs occurrence. IRM at 180 days was 8%, without differences among donor types (P = .106). In conclusion, study results did not show a significant impact of donor type on PE-BSI incidence; conversely, MUD and haploidentical transplants retained a higher occurrence of VIs in the early phase after HSCT.
异基因造血干细胞移植（HSCT）后使用环磷酰胺（PT-Cy）作为移植物抗宿主病（GVHD）预防的患者中，感染的发生率和结果在很大程度上尚不清楚。本研究旨在评估接受 PT-Cy 预处理的异基因 HSCT 患者的早期血液感染（PE-BSI）和病毒感染（VI；巨细胞病毒[CMV]、腺病毒[ADV]、人疱疹病毒 6[HHV6]和 BK 多瘤病毒出血性膀胱炎[BKPyV-HC]）的发生率、预测因素以及感染相关死亡率（IRM）。我们分析了 235 例患者：分别有 62%、21%和 17%接受了单倍体相合（haplo）、非亲缘供体（MUD）和亲缘供体移植。总体而言，72 例患者在 HSCT 后 13 天中位时间发生 77 次 PE-BSI 感染：28 天累积发病率（CIF）为 32%，不同供者类型之间无差异（P=0.988）。多变量分析显示，HSCT 前严重中性粒细胞减少症（校正风险比[AHR] = 2.90）和多重耐药革兰氏阴性菌直肠携带者（AHR=2.68）的患者发生 PE-BSI 的 CIF 更高。30 天的 IRM 为 5%，不同供者类型之间无差异（P=0.106）。总体而言，208 例患者在 HSCT 后 20 天中位时间首次发生≥1 种 VI（CMV、HHV6、ADV、BKPyV-HC）：90 天的 CIF 为 91%，MUD 和 haplo 明显更高（P=0.0089）。多变量分析显示，急性 GVHD 分级≥2 级（AHR=1.32）和宿主/供体 CMV 血清学不匹配（阳性/阳性与阴性/阴性：AHR=2.95，阳性/阴性与阴性/阴性：AHR=2.41，阴性/阳性与阴性/阴性：AHR=2.35）也影响 VI 的发生。180 天的 IRM 为 8%，不同供者类型之间无差异（P=0.106）。总之，研究结果表明，供者类型对 PE-BSI 发生率没有显著影响；相反，MUD 和单倍体相合移植在 HSCT 后早期仍有更高的 VI 发生率。
