Contributions
Abstract: S795
Type: Oral Presentation
Presentation during EHA22: On Sunday, June 25, 2017 from 08:15 - 08:30
Location: Room N105
Background
Research has recently highlighted the importance of healthy gut microbiota in the prevention of graft-versus-host disease (GVHD). Gut decontamination and the use of broad-spectrum antibiotics have led to the loss of natural microbiota diversity and the overgrowth of opportunistic pathogens with emerging antimicrobial resistence. However, the role of multi-drug resistant (MDR) bacteria in development of GVHD needs to be elucidated.
Aims
Our aim was to evaluate the impact of gut colonization with MDR bacteria on the acute GVHD and related outcome.
Methods
Results
Our study population included 88 male and 57 female patients who underwent allo-SCT at a median age of 46 years (range 18-64). Among them, most patiens were treated for myeloid malignancies (70%), while the rest had lymphoproliferative disorders and one patient had aplastic anemia. The donors were unrelated in 74 cases, related in 67 patients and haploidentical in 4 patients. Most of the patients (70%) received peripheral blood stem cells after a reduced-intensity conditioning regimen (56%). At the time of allo-SCT 37% patients were colonized with MDR bacteria, while another 19% became colonized in the early postransplantation period. Among colonized patients, 12% patients were colonized by VRE, 1% by MRSA, 43% by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, 27% by carbapenem-resistant Enterobacteriaceae (CRE), 9% by MDR Acinetobacter baumannii and 58% by MDR Pseudomonas aeruginosa. 36% patients were colonized with more than one MDR pathogen. The cumulative incidence (CI) of severe (grade III-IV) acute GVHD was significantly higher in patients colonized with MDR-GNB (27%, 95% CI, 19-39%) than in non-colonized patients (14%, 95% CI, 7-23%) (p=0.04). Moreover, MDR-GNB colonized patients had significantly more gastrointestinal (GI) GVHD CI as opposed to non-colonized patients (28% (95% CI, 20-41%) vs 14% (95% CI, 7-23%), p=0.02) and more acute GVHD-related mortality (16%, (95%CI, 9-26%) vs 7% (95%CI, 3-15%), p=0.10). A substantial and independent role of gut colonization with MDR-GNB on the development of GI GVHD was confirmed by multivariate analysis using time-dependent covariate functions for high risk disease, myeloablative conditioning, peripheral blood stem cells, unrelated donor (hazard ratio 2.14; 95%CI, 0.99-4.68, P=0.05), older age (hazard ratio 2.15; 95%CI, 1.00-4.59, P=0.04) and MDR-GNB gut colonization (hazard ratio 2.26;95% CI, 1.05-4.83, P=0.03).
Conclusion
In summary, this report shows a significant role of MDR-GNB in the pathogenesis of severe acute GVHD. To our knowledge, we are the first to show that gut colonization with MDR-GNB represents an independent risk factor for GI GVHD. With growing resistance and lack of efficient antibiotics, decolonization strategies as fecal microbiota transplantation become an attractive strategy for restoration of healthy gut flora and prevention of severe acute GVHD.
Session topic: 22. Stem cell transplantation - Clinical
Keyword(s): Hematopoietic cell transplantation, Acute graft-versus-host disease, Risk factor, Multidrug resistance
Abstract: S795
Type: Oral Presentation
Presentation during EHA22: On Sunday, June 25, 2017 from 08:15 - 08:30
Location: Room N105
Background
Research has recently highlighted the importance of healthy gut microbiota in the prevention of graft-versus-host disease (GVHD). Gut decontamination and the use of broad-spectrum antibiotics have led to the loss of natural microbiota diversity and the overgrowth of opportunistic pathogens with emerging antimicrobial resistence. However, the role of multi-drug resistant (MDR) bacteria in development of GVHD needs to be elucidated.
Aims
Our aim was to evaluate the impact of gut colonization with MDR bacteria on the acute GVHD and related outcome.
Methods
Results
Our study population included 88 male and 57 female patients who underwent allo-SCT at a median age of 46 years (range 18-64). Among them, most patiens were treated for myeloid malignancies (70%), while the rest had lymphoproliferative disorders and one patient had aplastic anemia. The donors were unrelated in 74 cases, related in 67 patients and haploidentical in 4 patients. Most of the patients (70%) received peripheral blood stem cells after a reduced-intensity conditioning regimen (56%). At the time of allo-SCT 37% patients were colonized with MDR bacteria, while another 19% became colonized in the early postransplantation period. Among colonized patients, 12% patients were colonized by VRE, 1% by MRSA, 43% by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, 27% by carbapenem-resistant Enterobacteriaceae (CRE), 9% by MDR Acinetobacter baumannii and 58% by MDR Pseudomonas aeruginosa. 36% patients were colonized with more than one MDR pathogen. The cumulative incidence (CI) of severe (grade III-IV) acute GVHD was significantly higher in patients colonized with MDR-GNB (27%, 95% CI, 19-39%) than in non-colonized patients (14%, 95% CI, 7-23%) (p=0.04). Moreover, MDR-GNB colonized patients had significantly more gastrointestinal (GI) GVHD CI as opposed to non-colonized patients (28% (95% CI, 20-41%) vs 14% (95% CI, 7-23%), p=0.02) and more acute GVHD-related mortality (16%, (95%CI, 9-26%) vs 7% (95%CI, 3-15%), p=0.10). A substantial and independent role of gut colonization with MDR-GNB on the development of GI GVHD was confirmed by multivariate analysis using time-dependent covariate functions for high risk disease, myeloablative conditioning, peripheral blood stem cells, unrelated donor (hazard ratio 2.14; 95%CI, 0.99-4.68, P=0.05), older age (hazard ratio 2.15; 95%CI, 1.00-4.59, P=0.04) and MDR-GNB gut colonization (hazard ratio 2.26;95% CI, 1.05-4.83, P=0.03).
Conclusion
In summary, this report shows a significant role of MDR-GNB in the pathogenesis of severe acute GVHD. To our knowledge, we are the first to show that gut colonization with MDR-GNB represents an independent risk factor for GI GVHD. With growing resistance and lack of efficient antibiotics, decolonization strategies as fecal microbiota transplantation become an attractive strategy for restoration of healthy gut flora and prevention of severe acute GVHD.
Session topic: 22. Stem cell transplantation - Clinical
Keyword(s): Hematopoietic cell transplantation, Acute graft-versus-host disease, Risk factor, Multidrug resistance