faecal microbiota transplantation (fmt) for clostridium difficile infection (cdi) in...

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Faecal microbiota transplantation (FMT) for Clostridium difficile infection (CDI) in immunocompromised (IC) pts: Efficacy and safety International, multi-centre, retrospective study: N=75 adult + 5 paediatric IC pts with CDI (79% outpatients): recurrent: 55% − refractory: 11% − severe (± recurrent/refractory): 34% → 32-item questionnaire soliciting demographic and pre- and post-FMT data Mean FU between FMT and data collection: 11 mo (range: 3-46 mo) Efficacy Kelly CR et al. Am J Gastroenterol 2014;109:1065-71 1 of 2 IBD: inflammatory bowel disease; IS: immunosuppressive

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Page 1: Faecal microbiota transplantation (FMT) for Clostridium difficile infection (CDI) in immunocompromised (IC) pts: Efficacy and safety International, multi-centre,

Faecal microbiota transplantation (FMT) for Clostridium difficile infection (CDI) in immunocompromised (IC) pts: Efficacy and safety

• International, multi-centre, retrospective study: N=75 adult + 5 paediatric IC pts with CDI (79% outpatients): recurrent: 55% − refractory: 11% − severe (± recurrent/refractory): 34%→ 32-item questionnaire soliciting demographic and pre- and post-FMT data

• Mean FU between FMT and data collection: 11 mo (range: 3-46 mo)

Efficacy

Kelly CR et al. Am J Gastroenterol 2014;109:1065-71

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IBD: inflammatory bowel disease; IS: immunosuppressive

Page 2: Faecal microbiota transplantation (FMT) for Clostridium difficile infection (CDI) in immunocompromised (IC) pts: Efficacy and safety International, multi-centre,

Faecal microbiota transplantation (FMT) for Clostridium difficile infection (CDI) in immunocompromised (IC) pts: Efficacy and safety

Safety (≤12 wk post-FMT)

•No infections related to FMT within 12 wk after FMT

•No significant ≠ in rate of AEs or SAEs between pts with and without IBD

In IC patients, FMT appears to be effective for the Tx of CDI, with few SAEs and Tx-related AEs, and no related infectious complications

Kelly CR et al. Am J Gastroenterol 2014;109:1065-71

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Page 3: Faecal microbiota transplantation (FMT) for Clostridium difficile infection (CDI) in immunocompromised (IC) pts: Efficacy and safety International, multi-centre,

Faecal microbiota transplantation (FMT) for Clostridium difficile infection (CDI) in immunocompromised (IC) pts: Efficacy and safety

Safety (≤12 wk post-FMT)

•No infections related to FMT within 12 wk after FMT

•No significant ≠ in rate of AEs or SAEs between pts with and without IBD

In IC patients, FMT appears to be effective for the Tx of CDI, with few SAEs and Tx-related AEs, and no related infectious complications

Kelly CR et al. Am J Gastroenterol 2014;109:1065-71

Page 4: Faecal microbiota transplantation (FMT) for Clostridium difficile infection (CDI) in immunocompromised (IC) pts: Efficacy and safety International, multi-centre,

Impact of donor cytomegalovirus (CMV) serological status on outcome of haematopoietic stem cell transplant (HSCT)

• Retrospective study (European Group for Blood and Marrow Transplantation database; 1992-2008): N=49,542 HSCT pts: Seropositive (R+): N=29,349 / Seronegative (R-): N=20,193

Ljungman P et al. Clin Infect Dis 2014;59:473-81

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Estimated 5-yr overall survival: Kaplan-Meier analysis; HR, P-values: multivariate Cox regression model

Page 5: Faecal microbiota transplantation (FMT) for Clostridium difficile infection (CDI) in immunocompromised (IC) pts: Efficacy and safety International, multi-centre,

Impact of donor cytomegalovirus (CMV) serological status on outcome of haematopoietic stem cell transplant (HSCT)

Result also valid when analysis was restricted to pts with myeloablative conditioning from yr 2000 onwards (N=21,813): HR=0.91; P=0.02

Ljungman P et al. Clin Infect Dis 2014;59:473-81

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Selecting a D+ unrelated donor may negatively impact survival compared with a D- in R- pts, but may positively impact survival in

R+ pts receiving a myeloablative conditioning regimen

Page 6: Faecal microbiota transplantation (FMT) for Clostridium difficile infection (CDI) in immunocompromised (IC) pts: Efficacy and safety International, multi-centre,

PTX3 SNPs: prognostic value for invasive aspergillosis in haematopoietic stem cell transplant (HSCT) pts

• Long pentraxin 3 (PTX3): soluble pattern-recognition receptor involved in immune resistance to Aspergillus fumigatus

Single-centre discovery study (2003-2011; Italy):

• N=268 adult pts undergoing HSCT + respective donors (98% related) → screened for PTX3 single nucleotide polymorphisms (SNPs)

• Multivariate analysis: Independent predictors of risk of invasive aspergillosis:

Cunha C et al. New Engl J Med 2014;370:421-32

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HR for presence vs absence of genotype or haplotype; adjusted for HLA-matching status, use or non-use of total-body irradiation in the myeloablative conditioning, and antifungal prophylaxis

Page 7: Faecal microbiota transplantation (FMT) for Clostridium difficile infection (CDI) in immunocompromised (IC) pts: Efficacy and safety International, multi-centre,

PTX3 SNPs: prognostic value for invasive aspergillosis in haematopoietic stem cell transplant (HSCT) pts

Multi-centre confirmation study:

•107 pts with invasive aspergillosis + 223 matched controls

•Multivariate analysis: Independent predictors of risk of invasive aspergillosis:

•Functional analysis: PTX3 deficiency in h2/h2 neutrophils → instability of messenger RNA → ability to phagocytose conidia of A. fumigatus and clear fungus: significantly impaired

Genetic deficiency of PTX3 may be associated with an increased risk of invasive aspergillosis in pts treated with HSCT, presumably by

affecting antifungal capacity of neutrophils

Cunha C et al. New Engl J Med 2014;370:421-32

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OR for presence vs absence of genotype or haplotype; adjusted for HLA-matching status, use or non-use of total-body irradiation in the myeloablative conditioning