Fecal filtrate transplantation as salvage therapy for fulminant Clostridioides difficile infection in adult hematological patients during chemotherapy-induced aplasia: a pilot experience.

Fulminant Clostridioides difficile infection (CDI) in patients with hematologic malignancies during chemotherapy-induced aplasia carries high mortality and limited treatment options. Our objective was to evaluate fecal filtrate transplantation (FFT) as a salvage therapy for fulminant CDI during aplasia, and to explore whether donor-recipient phage dynamics may contribute to clinical response. We conducted a single-center, prospective, protocol-defined pilot case series study including consecutive adults with hematologic malignancies, chemotherapy-induced grade-4 aplasia and fulminant CDI, refractory to ≥5 d of high-dose oral vancomycin plus intravenous metronidazole and tigecycline. FFT was prepared from a single unrelated donor using sequential centrifugation and filtration, and administered via nasogastric tube in two doses. The primary outcome was sustained clinical cure, secondary outcomes included survival and adverse events, assessed at +14 and +30 d post-FFT. 16S rRNA gene sequencing was used to assess microbiome compositions, while viral metagenomics and in vitro propagation assays were employed to characterize donor-recipient phageome interactions. Three patients with adverse-risk acute myeloid leukemia and fulminant CDI caused by genetically distinct C. difficile strains received FFT. All patients achieved clinical resolution by day +14, accompanied by improvements in abdominal distension and inflammatory markers. By day +30, one patient died from Pseudomonas aeruginosa septic shock, while two maintained remission with confirmatory follow-up. FFT was well tolerated, with no procedure-related immediate complications or FFT-attributable adverse events. Microbiome and phage profiling revealed heterogeneous responses, including shifts in bacterial community composition, with no clear evidence for a general role of donor-derived phages in CDI resolution. In contrast, we observed induction of prophages harbored by recipient-associated Clostridium species, which may have contributed to decolonization through stress-induced entry into the lytic cycle. FFT was feasible, with rapid sustained CDI resolution in hematologic patients with chemotherapy-induced aplasia. ClinicalTrials.gov identifier NCT07172191. Prospective single-center pilot study of fecal filtrate transplantation (FFT) for fulminant-refractory C. difficile infection in three aplastic adult hematologic patients. FFT was well tolerated, achieved rapid clinical cure, and showed heterogeneous microbiome and phageome modulation, potentially contributing to therapeutic effects.