Severity of acute gastrointestinal graft‐vs‐host disease is associated with incidence of bloodstream infection after adult allogeneic hematopoietic stem cell transplantation

Abstract

Background Infections are the most common cause of non‐relapse mortality in adult allogeneic hematopoietic stem cell transplant (allo HSCT) recipients. Acute gastrointestinal graft‐vs‐host disease (GI GVHD) often leads to friable mucosa as well as treatment interventions which can increase risk of infection. Our primary objective was to describe the relationship between increasing grades of acute GI GVHD and incidence of bloodstream infections (BSI). Methods We reviewed 441 adults who underwent allo HSCT from 2011 to 2017 and were clinically diagnosed with GI GVHD, non‐GI GVHD, or no GVHD based on the modified Glucksberg scale within the first 100 days of transplantation. The maximum grades of acute GI GVHD and non‐GI GVHD were used in the analysis. BSI was defined based on the presence of a blood culture positive for bacteria or fungi and treatment with antibiotics. The incidence of BSI within the first 180 days of transplantation was estimated with the cumulative incidence method. Fine and Gray regression was used to assess association between clinical grade of acute GI GVHD and BSI risk, adjusting for grade of non‐GI GVHD and for other significant baseline patient risk factors for BSI identified by multivariable analysis. Results are shown as hazard ratio (HR) and 95% confidence interval (CI). A similar analysis was conducted in 130 patients with histologic grade of acute GI GVHD. Results Overall BSI incidence by day 180 was 32%; gram‐negative bacilli were the predominant organisms, followed by gram‐positive cocci and fungi. Patients with grade 4 acute GI GVHD had higher risk of BSI as compared to patients with no GI GVHD (HR 2.98, CI 1.65‐5.37, P < .001), while those with grade 3 acute GI GVHD had similar BSI risk (HR 0.89, CI 0.36‐2.21, P = .81). Grade of GI GVHD had no association with risk of non‐BSI. Results were similar in patients with histologic grade acute GI GVHD. Patients who developed BSI or non‐BSI had significantly higher overall mortality risk compared to those without infectious complications (HR 2.52, CI 1.92‐3.31, P < .001 for BSI; HR 1.60, CI 1.20‐2.13, P = .001 for non‐BSI). Conclusions Grade 4 acute GI GVHD is associated with a higher risk of BSI, which is in turn associated with a higher risk of overall mortality in this population. Understanding the relationships between acute GI GVHD, BSI, and overall mortality can guide future treatment strategies for adult allo HSCT recipients.

Severe infections and infection-related mortality in a large series of haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide

“…Two-hundred thirty-six adult consecutive patients were transplanted between November 2013 and November 2018 in six centers of the Spanish transplant group (Grupo Español de Transplante Hematopoyético [GETH]). All patients received a haploSCT using PTCy as GvHD prophylaxis [ 16 ] followed by calcineurin inhibitors, with or without mycophenolate mofetil (MMF). Transplants were done according to the local institutional protocols, and all patients signed informed consent.…”

“…Bloodstream infections (BSI) are the most common severe infections and are a major cause of mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (alloSCT) [ 12 ], with an incidence ranging from 13 to 46% [ 13 ]. Many risk factors for BSI and severe infectious complications exist, such as prolonged severe neutropenia, myeloablative conditioning regimens, severe mucosal damage, use of broad-spectrum antibiotics; acute graft versus host disease, prolonged corticosteroids, and previous infectious history [ 13 – 16 ]. Moreover, delayed immune recovery, as seen with ex-vivo T cell-depleted alloSCT leads to high incidence of late infections in the haploSCT setting, as reported with the Perugia platforms [ 1 , 17 ].…”

Origins of bloodstream infections following fecal microbiota transplantation: a strain-level analysis

“…Previously reported BSI rate in patients with high-grade and steroid-resistance acute GVHD was approximately 50%. 15,16 The unusually high rate of BSIs in our population and the proximity between the infections and FMT suggested a potentially causal association. To trace the BSIs' source, we characterized host and donor stool samples as well as blood culture isolates by metagenomic sequencing.…”

“…In total, 33 BSIs, occurring up to 30 days after the last FMT, were observed in 15/22 (68%) patients. The median time from FMT to BSI was seven days (interquartile range [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]) (Table S2). Enterococcus faecium (10 events) and E. coli (6 events) were the most prevalent BSI-causing strains (Figure 1A; Table S3).…”

“…[5][6][7][8][9] High-grade acute GI GvHD is an established risk factor for BSI. 16 Since our trial was a single-arm study, we could not determine if the high BSI rates were caused, directly or indirectly, by the intervention.…”