MASCC/ISOO clinical practice statement: Current understanding on controversies in basic oral care in hemato-oncology and hematopoietic cell transplantation.

PURPOSE: A MASCC/ISOO Clinical Practice Statement (CPS) is aimed at generating a concise tool for clinicians, which concentrates on practical information needed for the management of oral complications of cancer patients. This CPS is focused on the current understanding of controversies that may arise while providing basic oral care in hemato-oncology patients and hematopoietic cell transplantation recipients (HCT). The CPS will summarize and elucidate controversies that have appeared in the literature and professional discussions. METHODS: This CPS was developed based on a critical evaluation of the literature followed by a structured discussion of a group of leading experts, members of the Oral Care Study Group of MASCC/ISOO. The information is presented in the form of succinct bullets to generate a short manual about the best standard of care. RESULTS: Controversies about the use of chlorhexidine (CHX) oral rinse, mechanical dental plaque removal procedures, the need for toothbrush replacement during phases of low blood cell counts, and the use of lidocaine mouthwash for oral pain were identified and discussed. Consensus about the best standard of care was outlined. CONCLUSION: The following ratifications are applicable for oral care in hemato-oncology patients and patients undergoing HCT: (1) CHX may reduce the risk of oral infections, although it was not found to reduce the risk of oral mucositis. (2) Toothbrushing and proficient interproximal cleaning should not be discouraged during HCT. (3) Toothbrushes do not need to be replaced daily and are preferred over cleansing swabs. (4) Lidocaine rinse, swish and spit, may be considered to palliate oral mucosal pain if applied in a certain manner.

From Pathogenesis to Intervention: The Importance of the Microbiome in Oral Mucositis.

Oral mucositis (OM) is a common and impactful toxicity of standard cancer therapy, affecting up to 80% of patients. Its aetiology centres on the initial destruction of epithelial cells and the increase in inflammatory signals. These changes in the oral mucosa create a hostile environment for resident microbes, with oral infections co-occurring with OM, especially at sites of ulceration. Increasing evidence suggests that oral microbiome changes occur beyond opportunistic infection, with a growing appreciation for the potential role of the microbiome in OM development and severity. This review collects the latest articles indexed in the PubMed electronic database which analyse the bacterial shift through 16S rRNA gene sequencing methodology in cancer patients under treatment with oral mucositis. The aims are to assess whether changes in the oral and gut microbiome causally contribute to oral mucositis or if they are simply a consequence of the mucosal injury. Further, we explore the emerging role of a patient's microbial fingerprint in OM development and prediction. The maintenance of resident bacteria via microbial target therapy is under constant improvement and should be considered in the OM treatment.

Longitudinal analysis at three oral sites links oral microbiota to clinical outcomes in allogeneic hematopoietic stem-cell transplant.

IMPORTANCE: The oral cavity is the ultimate doorway for microbes entering the human body. We analyzed oral microbiota dynamics in allogeneic hematopoietic stem-cell transplant recipients and showed that microbiota injury and recovery patterns were highly informative on transplant complications and outcomes. Our results highlight the importance of tracking the recipient's microbiota changes during allogeneic hematopoietic stem-cell transplant to improve our understanding of its biology, safety, and efficacy.

Commensal oral microbiota impacts ulcerative oral mucositis clinical course in allogeneic stem cell transplant recipients.

Oral mucositis (OM) is a complex acute cytotoxicity of antineoplastic treatment that affects 40-85% of patients undergoing hematopoietic stem-cell transplantation. OM is associated with prolonged hospitalization, increased extensive pharmacotherapy, need for parenteral nutrition, and elevated treatment costs. As OM onset relates to the mucosal microenvironment status, with a particular role for microbiota-driven inflammation, we aimed to investigate whether the oral mucosa microbiota was associated with the clinical course of OM in patients undergoing allogeneic hematopoietic stem-cell transplantation. We collected oral mucosa samples from 30 patients and analyzed the oral mucosa microbiota by 16S rRNA sequencing. A total of 13 patients (43%) developed ulcerative OM. We observed that specific taxa were associated with oral mucositis grade and time to oral mucositis healing. Porphyromonas relative abundance at preconditioning was positively correlated with ulcerative OM grade (Spearman ρ = 0.61, P = 0.028) and higher Lactobacillus relative abundance at ulcerative OM onset was associated with shortened ulcerative OM duration (P = 0.032). Additionally, we generated a machine-learning-based bacterial signature that uses pre-treatment microbial profiles to predict whether a patient will develop OM during treatment. Our findings suggest that further research should focus on host-microbiome interactions to better prevent and treat OM.

Dental Biofilm Microbiota Dysbiosis Is Associated With the Risk of Acute Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation.

Acute graft-versus-host disease (aGVHD) is one of the major causes of death after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Recently, aGVHD onset was linked to intestinal microbiota (IM) dysbiosis. However, other bacterial-rich gastrointestinal sites, such as the mouth, which hosts several distinctive microbiotas, may also impact the risk of GVHD. The dental biofilm microbiota (DBM) is highly diverse and, like the IM, interacts with host cells and modulates immune homeostasis. We characterized changes in the DBM of patients during allo-HSCT and evaluated whether the DBM could be associated with the risk of aGVHD. DBM dysbiosis during allo-HSCT was marked by a gradual loss of bacterial diversity and changes in DBM genera composition, with commensal genera reductions and potentially pathogenic bacteria overgrowths. High Streptococcus and high Corynebacterium relative abundance at preconditioning were associated with a higher risk of aGVHD (67% vs. 33%; HR = 2.89, P = 0.04 and 73% vs. 37%; HR = 2.74, P = 0.04, respectively), while high Veillonella relative abundance was associated with a lower risk of aGVHD (27% vs. 73%; HR = 0.24, P < 0.01). Enterococcus faecalis bloom during allo-HSCT was observed in 17% of allo-HSCT recipients and was associated with a higher risk of aGVHD (100% vs. 40%; HR = 4.07, P < 0.001) and severe aGVHD (60% vs. 12%; HR = 6.82, P = 0.01). To the best of our knowledge, this is the first study demonstrating that DBM dysbiosis is associated with the aGVHD risk after allo-HSCT.