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Significant salivary changes in relation to oral mucositis following autologous hematopoietic stem cell transplantation.

ABSTRACT: The aim of this multicentre, longitudinal study was to determine salivary changes in relation to oral mucositis (OM) in multiple myeloma patients following high-dose melphalan and autologous hematopoietic stem cell transplantation (ASCT). Unstimulated and stimulated whole-mouth saliva samples (UWS and SWS) were collected before ASCT, 1×/wk during the hospitalisation phase, and 3 and 12 months post-ASCT. During the hospitalisation period OM was scored 3×/wk (WHO system). Flow rate, pH, total protein concentration (Nanodrop), albumin, lactoferrin, neutrophil defensin-1 (HNP1), total IgA and S100A8/A9 (ELISA) were determined. Mixed models were used to evaluate differences between ulcerative (u)OM (≥2 WHO, n = 20) and non-uOM (n = 31) groups. Until 18 days after ASCT, flow rate, pH, total IgA and HNP1 levels decreased in UWS and/or SWS, while log lactoferrin levels were significantly increased (UWS: p = 0.016 95% CI [0.36, 3.58], SWS: p < 0.001 95% CI [1.14, 3.29]). Twelve months post-ASCT, salivary protein levels were similar to baseline except for log total IgA, which was higher (UWS: p < 0.001 95% CI [0.49, 1.29], SWS: p < 0.001 95% CI [0.72, 1.45]). No differences between uOM and non-uOM groups were observed. Changes in salivary proteins indicated an inflammatory reaction in salivary glands coinciding with mucosal and systemic reactions in response to high-dose melphalan.

SUBMITTER: van Leeuwen SJM

PROVIDER: S-EPMC8189903 | biostudies-literature |

REPOSITORIES: biostudies-literature

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The salivary proteome in relation to oral mucositis in autologous hematopoietic stem cell transplantation recipients: a labelled and label-free proteomics approach.

Project description:BackgroundOral mucositis is a frequently seen complication in the first weeks after hematopoietic stem cell transplantation recipients which can severely affects patients quality of life. In this study, a labelled and label-free proteomics approach were used to identify differences between the salivary proteomes of autologous hematopoietic stem cell transplantation (ASCT) recipients developing ulcerative oral mucositis (ULC-OM; WHO score ≥ 2) or not (NON-OM).MethodsIn the TMT-labelled analysis we pooled saliva samples from 5 ULC-OM patients at each of 5 timepoints: baseline, 1, 2, 3 weeks and 3 months after ASCT and compared these with pooled samples from 5 NON-OM patients. For the label-free analysis we analyzed saliva samples from 9 ULC-OM and 10 NON-OM patients at 6 different timepoints (including 12 months after ASCT) with Data-Independent Acquisition (DIA). As spectral library, all samples were grouped (ULC-OM vs NON-OM) and analyzed with Data Dependent Analysis (DDA). PCA plots and a volcano plot were generated in RStudio and differently regulated proteins were analyzed using GO analysis with g:Profiler.ResultsA different clustering of ULC-OM pools was found at baseline, weeks 2 and 3 after ASCT with TMT-labelled analysis. Using label-free analysis, week 1-3 samples clustered distinctly from the other timepoints. Unique and up-regulated proteins in the NON-OM group (DDA analysis) were involved in immune system-related processes, while those proteins in the ULC-OM group were intracellular proteins indicating cell lysis.ConclusionsThe salivary proteome in ASCT recipients has a tissue protective or tissue-damage signature, that corresponded with the absence or presence of ulcerative oral mucositis, respectively.Trial registrationThe study is registered in the national trial register (NTR5760; automatically added to the International Clinical Trial Registry Platform).

| S-EPMC10329372 | biostudies-literature

The salivary proteome in relation to oral mucositis in autologous hematopoietic stem cell transplantation recipients: a labelled and label-free proteomics approach -DIAdata

Project description:Decreased salivary flow rates and/or changes in protein composition reported after autologous hematopoietic stem cell transplantation (ASCT) reduces the protective function of saliva. This might be associated with the development of oral mucositis (OM), an inflammation of the oral mucosa as a result of chemotherapy before ASCT which affects patients, quality of life and risk factor for systemic infections. In this study, a TMT-labelled proteomics experiment, a label-free quantification (LFQ) proteomics experiment and a DIA-MS proteomics experiment were used to identify differences in the salivary proteome between patients with ulcerative OM (uOM; WHO score 2) and those without (nOM).

2023-07-10 | PXD033525 | Pride

The salivary proteome in relation to oral mucositis in autologous hematopoietic stem cell transplantation recipients: a labelled and label-free proteomics approach-TMTdata

Project description:Decreased salivary flow rates and/or changes in protein composition reported after autologous hematopoietic stem cell transplantation (ASCT) reduces the protective function of saliva. This might be associated with the development of oral mucositis (OM), an inflammation of the oral mucosa as a result of chemotherapy before ASCT which affects patients? quality of life and risk factor for systemic infections. In this study, a TMT-labelled proteomics experiment, a label-free quantification (LFQ) proteomics experiment and a DIA-MS proteomics experiment were used to identify differences in the salivary proteome between patients with ulcerative OM (uOM; WHO score ? 2) and those without (nOM). For the TMT-labelled experiment, saliva samples of 5 uOM and 5 nOM were pooled at different time points: baseline, 1, 2, and 3 weeks after ASCT and 3 months after ASCT. A different salivary proteome was suggested by a distinct clustering of the OM pools at baseline, week 2 and week 3 after ASCT.

2023-07-10 | PXD033603 | Pride

The salivary proteome in relation to oral mucositis in autologous hematopoietic stem cell transplantation recipients: a labelled and label-free proteomics approach-DDALFQ

Project description:Decreased salivary flow rates and/or changes in protein composition reported after autologous hematopoietic stem cell transplantation (ASCT) reduces the protective function of saliva. This might be associated with the development of oral mucositis (OM), an inflammation of the oral mucosa as a result of chemotherapy before ASCT which affects patients? quality of life and risk factor for systemic infections. In this study, a TMT-labelled proteomics experiment, a label-free quantification (LFQ) proteomics experiment and a DIA-MS proteomics experiment were used to identify differences in the salivary proteome between patients with ulcerative OM (uOM; WHO score ? 2) and those without (nOM). For the TMT-labelled experiment, saliva samples of 5 uOM and 5 nOM were pooled at different time points: baseline, 1, 2, and 3 weeks after ASCT and 3 months after ASCT. A different salivary proteome was suggested by a distinct clustering of the OM pools at baseline, week 2 and week 3 after ASCT.

2023-07-10 | PXD033591 | Pride

Patterns of salivary microbiota injury and oral mucositis in recipients of allogeneic hematopoietic stem cell transplantation.

Project description:Oral mucositis (OM) is a common debilitating dose-limiting toxicity of cancer treatment, including hematopoietic stem cell transplantation (HSCT). We hypothesized that the oral microbiome is disturbed during allogeneic HSCT, partially accounting for the variability in OM severity. Using 16S ribosomal RNA gene sequence analysis, metabolomic profiling, and computational methods, we characterized the behavior of the salivary microbiome and metabolome of 184 patients pre- and post-HSCT. Transplantation was associated with a decrease in oral α diversity in all patients. In contrast to the gut microbiome, an association with overall survival was not detected. Among 135 patients given methotrexate for graft-versus-host disease prophylaxis pre-HSCT, Kingella and Atopobium abundance correlated with future development of severe OM. Posttransplant, Methylobacterium species were significantly enriched in patients with severe OM. Moreover, the oral microbiome and metabolome of severe OM patients underwent distinct changes post-HSCT, compared with patients with no or mild OM. Changes in specific metabolites were well explained by microbial composition, and the common metabolic pathway was the polyamines pathway, which is essential for epithelial homeostasis. Together, our findings suggest that salivary microbial composition and metabolites are associated with the development of OM, offering new insights on pathophysiology and potential avenues of intervention.

| S-EPMC7362373 | biostudies-literature

Association of HSV-1 and Reduced Oral Bacteriota Diversity with Chemotherapy-Induced Oral Mucositis in Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation.

Project description:Oral mucositis (OM) is a common complication of chemotherapy and remains a significant unmet need. The aim of this study was to investigate the role of oral bacteriota and HSV-1 in OM. Forty-six patients admitted for autologous hematopoietic stem cell transplantation were longitudinally evaluated for OM, Candida, HSV-1, and leukocyte count, and buccal mucosal bacterial samples were obtained during their admission period. The bacterial communities collected at the baseline and post-chemotherapy, chosen from the time with the highest severity, were analyzed by sequencing the 16S rRNA gene. Twenty (43.5%) patients developed OM, the severity of which ranged from 1 to 5 according to the Oral Mucositis Assessment Scale (OMAS). Chemotherapy significantly increased the prevalence of HSV-1 detection but not that of Candida. The bacterial communities of patients after conditioning chemotherapy were characterized by aberrant enrichment of minor species and decreased evenness and Shannon diversity. After adjustment for age, gender, and neutropenia, the presence of HSV-1 was associated with the incidence of OM (odds ratio = 3.668, p = 0.004), while the decrease in Shannon diversity was associated with the severity of OM (β = 0.533 ± 0.220, p = 0.015). The control of HSV-1 and restoration of oral bacterial diversity may be a novel option to treat or prevent OM.

| S-EPMC7230275 | biostudies-literature

Pharmacoeconomic analysis of palifermin to prevent mucositis among patients undergoing autologous hematopoietic stem cell transplantation.

Project description:Trials have shown benefits of palifermin in reducing the incidence and severity of oral mucositis in patients with hematological malignancies undergoing autologous hematopoietic stem cell transplantation (HSCT) with total body irradiation (TBI)-based conditioning regimens. Similar outcome data are lacking for patients receiving non-TBI-based regimens. We performed a retrospective evaluation on the pharmacoeconomic benefit of palifermin in the setting of non-TBI-based conditioning and autologous HSCT. Between January 2002 and December 2010, 524 patients undergoing autologous HSCT for myeloma (melphalan 200 mg/m²) and lymphoma (high-dose busulfan, cyclophosphamide, and etoposide) as preparative regimen were analyzed. Use of patient-controlled analgesia (PCA) was significantly lower in the palifermin-treated groups (myeloma: 13% versus 53%, P < .001; lymphoma: 46% versus 68%, P < .001). Median total transplant charges were significantly higher in the palifermin-treated group, after controlling for inflation (myeloma: $167,820 versus $143,200, P < .001; lymphoma: $168,570 versus $148,590, P < .001). Palifermin treatment was not associated with a difference in days to neutrophil engraftment, length of stay, and overall survival and was associated with an additional cost of $5.5K (myeloma) and $14K (lymphoma) per day of PCA avoided. Future studies are suggested to evaluate the cost-effectiveness of palifermin compared with other symptomatic treatments to reduce transplant toxicity using validated measures for pain and quality of life.

| S-EPMC4063211 | biostudies-literature

Sleep disruption among cancer patients following autologous hematopoietic cell transplantation.

Project description:Despite a high prevalence of sleep disruption among hematopoietic cell transplant (HCT) recipients, relatively little research has investigated its relationships with modifiable cognitive or behavioral factors or used actigraphy to characterize sleep disruption in this population. Autologous HCT recipients who were 6-18 months post transplant completed self-report measures of cancer-related distress, fear of cancer recurrence, dysfunctional sleep cognitions, and inhibitory sleep behaviors upon enrollment. Patients then wore an actigraph for 7?days and completed a self-report measure of sleep disruption on day 7 of the study. Among the 84 participants (age M?=?60, 45% female), 41% reported clinically relevant sleep disruption. Examination of actigraph data confirmed that, on average, sleep was disrupted (wake after sleep onset M?=?66?min) and sleep efficiency was less than recommended (sleep efficiency M?=?78%). Cancer-related distress, fear of recurrence, dysfunctional sleep cognitions, and inhibitory sleep behaviors were related to self-reported sleep disruption (p values<0.05) but not objective sleep indices. Results suggest that many HCT recipients experience sleep disruption after transplant. Cancer-related distress, fear of recurrence, dysfunctional sleep cognitions, and maladaptive sleep behaviors are related to self-reported sleep disruption and should be considered targets for cognitive behavioral intervention in this population.

| S-EPMC5851802 | biostudies-literature

A randomized phase II study of acyclovir for the prevention of chemotherapy-induced oral mucositis in patients undergoing autologous hematopoietic stem cell transplantation.

Project description:ObjectivesTo prove our hypothesis that acyclovir prophylaxis in autologous hematopoietic stem cell transplantation (AHSCT) recipients with hematologic malignancies (HM) reduces the incidence of chemotherapy-induced oral mucositis (CIOM) by inhibiting the intraoral HSV reactivation during the neutropenic period, we conducted a randomized phase II study of acyclovir for the prevention of CIOM in adult HSV sero-positive AHSCT recipients.MethodsPatients were randomized to either the study group (acyclovir 400 mg PO bid until neutrophil engraftment) or the control group (no prophylaxis) and received AHSCT. Oral examination and sampling for HSV were performed at three timepoints of AHSCT.ResultsIn 54 patients who were randomized (for intention-to-analysis), the incidence of CIOM was 16.0% (4/25 patients) and 58.6% (17/29 patients) in the study group and the control group, respectively (P = 0.001). In 49 patients who completed the study (for per-protocol analysis), the incidence of CIOM was 13.0% (3/23 patients) and 61.5% (16/26 patients) in the study group and the control group, respectively (P = 0.001). In addition, HSV-1 PCR positivity in the study group was significantly lower than that the control group (4.3% vs. 46.2%, P = 0.001). A strong association between the HSV-1 reactivation status and CIOM was reconfirmed.ConclusionsProphylactic use of oral acyclovir effectively reduced the incidence of CIOM in patients with HM who were undergoing AHSCT.Trial registrationsThis trial was registered at the Clinical Research Information Service in the Republic of Korea under the number KCT0003885 (registration date 03/05/2019).

| S-EPMC10724996 | biostudies-literature

Salivary Osteopontin as a Potential Biomarker for Oral Mucositis.

Project description:Osteopontin (OPN), a multifunctional phosphoglycoprotein also presents in saliva, plays a crucial role in tumour progression, inflammation and mucosal protection. Mucosal barrier injury due to high-dose conditioning regimen administered during autologous and allogeneic peripheral stem cell transplantation (APSCT) has neither efficient therapy nor established biomarkers. Our aim was to assess the biomarker role of OPN during APSCT, with primary focus on oral mucositis (OM). Serum and salivary OPN levels were determined by ELISA in 10 patients during APSCT at four stages of transplantation (day -3/-7, 0, +7, +14), and in 23 respective healthy controls. Results: There was a negative correlation between both salivary and serum OPN levels and grade of OM severity during APSCT (r = -0.791, p = 0.019; r = -0.973, p = 0.001). Salivary OPN increased at days +7 (p = 0.011) and +14 (p = 0.034) compared to controls. Among patients, it was higher at day +14 compared to the time of admission (day -3/-7) (p = 0.039) and transplantation (day 0) (p = 0.011). Serum OPN remained elevated at all four stages of transplantation compared to controls (p = 0.013, p = 0.02, p = 0.011, p = 0.028). During APSCT elevated salivary OPN is a potential non-invasive biomarker of oral mucositis whereas the importance of high serum OPN warrants further studies.

| S-EPMC8066152 | biostudies-literature

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