Clinical Features and Risk Factors of Post-Engraftment Bloodstream Infection in Allogeneic HCT

[Introduction]

Bloodstream infection (BSI) is a serious complication of HCT that may be life-threatening. BSI frequently occurs before neutrophil engraftment (pre-engraftment BSI), but has also been reported after neutrophil recovery (post-engraftment BSI). In contrast to pre-engraftment BSI, the clinical features and risk factors of post-engraftment BSI remain unclear.

[Aims]

We investigated the clinical characteristics of and risk factors for post-engraftment BSI.

[Methods]

This retrospective study included 176 adult patients who underwent HCT and achieved neutrophil engraftment between 2006 and 2017 at our institute. Diagnoses consisted of AML (n=86), ALL (n=36), MDS (n=21), MPN (n=4), CML (n=1), ATL (n=6), aplastic anemia (n=6), and malignant lymphoma (n= 16). The median age at HCT was 42 y (range 16-67 y). Graft sources were BM (n=69), PB (n=57), and CB (n=50). Fifty-five patients (31.2%) had a high (≥3) HCT-CI score on HCT. Sixty-four patients (36.4%) received HCT with an advanced disease status. Fluoroquinolone (FQ) as prophylaxis was administered to 89 patients (50.6%). Central venous catheters (CV) were inserted in all patients before HCT. All patients consulted a dentist before HCT and received guidance on appropriate oral self-care to prevent severe oral mucositis; 92 (52.3%) continuously received intensive oral care after HCT (I-care; visit to a dentist at least once a week until neutrophil engraftment for the assessment of oral mucositis and cleaning), whereas 84 (47.7%) only performed oral self-care (S-care; according to guidance by a dentist). In the present study, BSI was defined as an infectious state with fever (≥38°C) and the isolation of a pathogen on at least 1 blood culture or on 2 or more if a common skin contaminant was isolated. Post-engraftment BSI was evaluated until day 180.

[Results]

Seventy-five events of BSI (in 69 patients) occurred until day 180. The total cumulative incidence of BSI (CIB) was 39.2%. The CIB of pre- and post-engraftment BSI were similar at 21.6% (n=38) and 21.0% (n=37) (p=1.0), respectively. Six patients developed pre- and post-engraftment BSI. CV was inserted in all patients when BSI occurred. Twenty-five pathogens were isolated in the present study. Regarding the type of pathogen, Gram-positive cocci were the most common in pre-/post-engraftment BSI (63.2%/69.0%). Gram-negative (29.0%/14.3%) and -positive rods (15.8%/19.0%) were detected. Staphylococcus epidermidis was the most frequently detected species in pre/post-engraftment BSI (31.6%/57.1%). Similar to CIB, no significant difference was observed in the pathogens identified between pre-/post-engraftment BSI (p=0.34).

We performed further analyses to identify risk factors for post-engraftment BSI. In Fisher's exact test as a univariate analysis, HCT-CI≥3 (p=0.045), TBI≥3 Gy (p=0.041), not administered FQ (p=0.042), no I-care (p=0.003), and a graft source of BM (p=0.002) were identified as risk factors for post-engraftment BSI. Age (p=0.25), conditioning (p=0.197), repeated HCT (0.607), disease stage prior to HCT (p=0.701), and a history of pre-engraftment BSI (p=0.501) did not contribute to post-engraftment BSI. A logistic regression test with backward stepwise selection based on p-values as the multivariate analysis revealed that I-care (OR 0.358, 95%CI: 0.16-0.801, p=0.0124) and a graft source of PB (OR 0.322, 95%CI: 0.124-0.837, p=0.02) reduced the risk of post-engraftment BSI.

Furthermore, to confirm the impact of the oral care type on post-engraftment BSI, we compared the CIB of the S- and I-care groups. The CIB of pre-engraftment BSI was similar between the I- and S-care groups (21.4% vs 21.7%, p=1), whereas that of post-engraftment BSI was significantly lower in the I-care group (12.0% vs 29.8%, p<0.001) than in the S-care group.

[Conclusion]

CIB and isolated pathogens were similar between pre- and post-engraftment BSI, even if neutrophils had recovered sufficiently. Since BSI may occur at any time during transplantation, careful follow-ups are needed. Intensive oral care by a dental specialist may reduce the risk of post-engraftment BSI.