To answer a third question – What is the natural history of recovery from microbiota injury after HCT? – the investigators looked at trends over time for 28 allogeneic HCT recipients. With a total of 294 samples for analysis, Dr. Peled and his group found that “diversity increases, but often to a configuration distinct from the pre-HCT state.” It took some patients nearly a year to return to their pretransplant level of diversity.
Patients in the subset of those who go on to develop lower gastrointestinal GVHD have an intestinal microbiota composition that is distinct from those patients whose GVHD exclusively involved the upper gastrointestinal tract, the skin, or the liver (P = .019), Dr. Peled said.
He and his team are currently enrolling patients for a phase 2 randomized clinical trial (NCT03078010) that will explore strategies to deescalate the use of broad-spectrum antibiotics for febrile neutropenia in patients with allogeneic HCT. The trial will randomize patients to receive either piperacillin-tazobactam, the current standard of care at MSKCC, or cefepime with deescalation to aztreonam with vancomycin, the microbiota-sparing strategy. The trial will examine the abundance of Clostridiales and Blautia species, gut biodiversity, the rate of GVHD, bacteremia, and survival rates.
The research presented was funded by the Parker Institute for Cancer Immunotherapy, the Sawiris Foundation, Empire Clinical Research Investigator Program, and Seres Therapeutics. Dr. Peled reported that he has intellectual property rights and research funding through Seres Therapeutics