Interventional antibiotic treatment replacing antibiotic prophylaxis during allogeneic hematopoietic stem cell transplantation is safe and leads to a reduction of antibiotic administration.

Patients undergoing allogeneic hematopoietic stem cell transplantation (alloHSCT) face an elevated risk of infection-related mortality, particularly during the pre-engraftment period. Although systemic antibiotic prophylaxis (SAP) is commonly employed during neutropenia, it is linked to disruptions in the intestinal microbiome, increasing the risk of graft-versus-host disease (GVHD), Clostridium difficile infection (CDI), and colonization with multi-drug resistant (MDR) bacteria. In our retrospective analysis, we evaluated the safety and efficacy of an exclusively interventional antibiotic treatment (IAT) compared to SAP in adult alloHSCT patients. In comparison to SAP, IAT resulted in a significantly reduced duration of antibiotic therapy (24 vs. 18 days, p < 0.001), although the cumulative incidence (CI) of bloodstream infections (BSI) by day + 100 post-HSCT was significantly higher in the IAT group compared to SAP (40% vs. 13%, p < 0.001). However, this did not lead to a significant increase in ICU transfers (13% vs. 6%, p = ns) or a higher CI of non-relapse mortality (NRM) at 3 years (11% vs. 10%, p = ns). With a median follow-up of 1052 days, the 3-year overall survival (OS) rates were 69% and 66% for the SAP and IAT cohorts, respectively (p = ns). The CI of acute GVHD grade II-IV (30% vs. 39%) at 100 days or chronic GVHD of any grade (50% vs. 45%) at 3 years did not differ significantly between the SAP and IAT groups. There was a tendency towards a higher CI of severe chronic GVHD in the SAP cohort (28% vs. 13%, p = 0.08). Our single center experience in conducting alloHSCT without antibiotic prophylaxis but with stringent guidelines for prompt antibiotic intervention demonstrated no disadvantages in terms of OS and NRM. IAT led to significantly reduced consumption of cefotaxime, carbapenem, and glycopeptide antibiotics. In conclusion, our findings suggest that replacing SAP with the proposed IAT procedure is both safe and feasible.

Functional Dominance of CHIP-Mutated Hematopoietic Stem Cells in Patients Undergoing Autologous Transplantation.

Clonal hematopoiesis of indeterminate potential (CHIP) is caused by recurrent somatic mutations leading to clonal blood cell expansion. However, direct evidence of the fitness of CHIP-mutated human hematopoietic stem cells (HSCs) in blood reconstitution is lacking. Because myeloablative treatment and transplantation enforce stress on HSCs, we followed 81 patients with solid tumors or lymphoid diseases undergoing autologous stem cell transplantation (ASCT) for the development of CHIP. We found a high incidence of CHIP (22%) after ASCT with a high mean variant allele frequency (VAF) of 10.7%. Most mutations were already present in the graft, albeit at lower VAFs, demonstrating a selective reconstitution advantage of mutated HSCs after ASCT. However, patients with CHIP mutations in DNA-damage response genes showed delayed neutrophil reconstitution. Thus, CHIP-mutated stem and progenitor cells largely gain on clone size upon ASCT-related blood reconstitution, leading to an increased future risk of CHIP-associated complications.