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1.
Utilization of Photobiomodulation for the Prevention and Treatment of Oral Mucositis
Pritchard, M., Ogg, S. W., Bosi, J., Mandrell, B. N.
Journal of pediatric hematology/oncology nursing. 2024;:27527530231214525
Abstract
Background: Oral mucositis is a significant and common toxicity experienced by patients who receive high-dose chemotherapy as a preparatory regimen for a hematopoietic cell transplant (HCT). Photobiomodulation (PBM) has been found to be feasible with significant efficacy in preventing the progression of oral mucositis in adult patients undergoing HCT. The purpose of this study was to determine the feasibility and efficacy of PBM in pediatric oncology patients undergoing HCT. Method: Forty children and adolescents admitted to the transplant unit for an allogeneic HCT for acute lymphoblastic leukemia or acute myeloid leukemia were treated daily at six sites until day + 20 or engraftment. Results: There were 1,035 patient encounters, with successful treatment of four or more sites during 979 patient encounters for a feasibility 93.3% CI [0.926, 0.039]. We had estimated a meaningful effect size of 20% for PBM and estimated 51% of patients treated with PBM would have at least one day or more of Grade 3 mucositis. The rate of patients who received PBM and developed Grade 3 mucositis was 20% CI [0.091, 0.356]. Patients treated with PBM had fewer days of hospitalization (p = .009) and less severe mucositis in comparison to the matched control group (p = .03). Conclusion: PBM is feasible and effective in preventing and treating oral mucositis and is now supported by the Children's Oncology Group for prevention and treatment of oral mucositis in patients undergoing an allogeneic HCT or receiving head/neck radiation.
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2.
Grading of minor salivary gland immuno-histopathology post-allogenic hematopoietic cell transplantation
Tollemar, V., Arvidsson, H., Häbel, H., Tudzarovski, N., Legert, K. G., Le Blanc, K., Warfvinge, G., Sugars, R. V.
Heliyon. 2023;9(4):e15517
Abstract
The oral cavity commonly displays mucosal lichenoid lesions and salivary gland dysfunction, which are considered different chronic Graft-versus-Host Disease (cGVHD) pathophysiology's. However, diagnostics of salivary gland (sg-)cGVHD are limited. The objectives of the current study are to evaluate the minor salivary gland (MSG) histo-immunopathological profiles post allogenic hematopoietic cell transplantation based on sg-cGVHD criteria. Design: Histopathology was characterized according to two published grading strategies. Firstly, the National Institute of Health (NIH) assessed peri-ductal/acinar infiltration, exocytosis, damage, and fibrosis, and a points-based grading scheme was established (0-16 points, Grade (G) 0 to IV). Second, a modified Sjögren's Syndrome focus-score with parenchymal damage was also adapted, (0-10 points, Score 0 to 2). 146 MSG biopsies from 79 patients were compared, using the histopathological specific criteria for sg-cGVHD pathology. Quantitative immunohistochemistry for T-cells (CD4, CD8), B-cells (CD19, CD20), monocytic cells (CD68) and dendritic cells (CD1a) were also assessed. Results: The large-scale cohort validated the use of both grading schemes. GIII-GIV and score 2 signified a histopathological diagnosis of "likely" sg-cGVHD. Immunopathological severity was associated with increased T-cells (CD4 and CD8) and monocytic (CD68) infiltrate, with minimal involvement of B-cells (CD19 and CD20), and Langerhans cells (CD1a). Conclusions: Both schemes were verified as being suitable for histological grading to improve assessment and diagnosis of sg-cGVHD. The NIH cGVHD grading appears to be more beneficial for research purposes, including final diagnostics of "no/inactive", "possible" or "likely" cGVHD. The study highlights the intricacies of sg-cGVHD pathology; and the need for standardized assessment to improve patient management associated to sg-cGVHD.
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3.
Incidence, severity, and temporal development of oral complications in pediatric allogeneic hematopoietic stem cell transplant patients - a multicenter study
Agholme, M. B., Dahllöf, G., Törlén, J. K., Majorana, A., Brennan, M. T., von Bültzingslöwen, I., Tan, P. L., Hu, S., Sim, Y. F., Hong, C.
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 2023;31(12):702
Abstract
PURPOSE Oral mucositis is a common complication for patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) and causes pain and difficulties in functions like eating and swallowing, resulting in lower quality of life and greater need of treatment with opioids and parenteral nutrition. This prospective multicenter study focused on pediatric recipients of HSCT in the neutropenic phase concerning oral complications, timing, severity, and patient experience. METHODS The cohort comprised 68 patients, median age 11.1 years (IQR 6.3) receiving allogeneic HSCT at three clinical sites. Medical records were retrieved for therapy regimens, concomitant medications, oral and dental history, and subjective oral complaints. Calibrated dentists conducted an oral and dental investigation before HSCT. After HSCT graft infusion, study personnel made bedside assessments and patients filled out a questionnaire once or twice a week until neutrophil engraftment. RESULTS We followed 63 patients through the neutropenic phase until engraftment. 50% developed oral mucositis of grades 2-4. Peak severity occurred at 8-11 days after stem cell infusion. Altogether, 87% had subjective oral complaints. The temporal distribution of adverse events is similar to the development of oral mucositis. The most bothersome symptoms were blisters and oral ulcerations, including mucositis; 40% reported severe pain and major impact on activities of daily living despite continuous use of opioids. CONCLUSION This study highlights the burden of oral complications and their negative effect on the health and quality of life of HSCT recipients.
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4.
Protective effect of cryotherapy against oral mucositis among allogeneic hematopoietic stem cell transplant recipients using melphalan-based conditioning
Oku, S., Futatsuki, T., Imamura, Y., Hikita, H., Inada, A., Mizutani, S., Mori, Y., Kashiwazaki, H.
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 2023;31(9):521
Abstract
PURPOSE Oral cryotherapy is an effective method to prevent oral mucositis (OM) induced by chemotherapeutic agents, such as melphalan (Mel). However, there is limited data about cryotherapy in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients; thus, the current study aimed to examine the efficacy of cryotherapy among allo-HSCT recipients treated with Mel-containing regimens. METHODS Medical records of 78 consecutive allo-HSCT recipients were retrospectively analyzed. Baseline characteristics and clinical courses between the patients who received cryotherapy (cryotherapy group, n = 42) and those who did not (control group, n = 36) were compared, especially focusing on methotrexate (MTX) use as a part of graft-versus-host disease (GVHD) prophylaxis. RESULTS Binary logistic regression analysis revealed that a higher dose of Mel (OR, 3.82; 95%CI, 1.085-13.46; P = 0.037) or MTX use (OR, 7.61; 95% CI, 2.41-23.97; P < 0.001) was associated with the incidence of OM. MTX use was also significantly associated with the duration of OM (β = 0.515; 95% CI, 9.712-21.636; P < 0.001). Among 31 patients without MTX use, cryotherapy was associated with a significant reduction of OM development (0% in the cryotherapy group vs 35% in the control group, P = 0.021). We did not find such an association in 47 patients with MTX use. CONCLUSION Cryotherapy was useful to prevent the incidence of OM in allo-HSCT recipients in the cases without MTX for GVHD prophylaxis.
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5.
Effect of ruxolitinib on the oral mucosa of patients with steroid-refractory chronic Graft-versus-Host disease and oral involvement
Kaurinovic, M., Delli, K., Jonk, A. E., Biswana, A., Hazenberg, C. L. E., Choi, G., de Groot, M. R., Morsink, L. M., Vissink, A., Bellido, M.
Clinical oral investigations. 2022
Abstract
BACKGROUND Chronic Graft-versus-Host Disease (cGVHD) can impact quality of life, especially in patients with oral involvement. Half of the patients with cGVHD do not respond to first-line therapy with corticosteroids and calcineurin inhibitors. Ruxolitinib is effective in steroid-refractory (SR)-cGVHD cases, but the long-term effects of ruxolitinib on the oral mucosa are unknown. OBJECTIVE(S): This study aims to assess the effect of ruxolitinib on the oral mucosa of SR-cGVHD patients with oral involvement. MATERIALS AND METHODS An observational longitudinal patient study was conducted in 53 patients with SR-cGVHD and oral involvement who were treated with ruxolitinib. The baseline condition of the oral mucosa was compared to its condition at 4 and 12 weeks after starting ruxolitinib. RESULTS The overall response was 81% (43/53), with a complete response in 53% (28/53) and partial response in 28% (15/53) after 12 weeks (p < 0.001). Men and patients concurrently using immunosuppressive therapy responded better than women (p = 0.005) and patients with ruxolitinib monotherapy (p = 0.02), respectively. At a longer follow-up (median 20 months), oral symptoms were comparable to the 12-week symptoms (p = 0.78), regardless of ruxolitinib use (p = 0.83). CONCLUSION Ruxolitinib treatment of SR-cGVHD patients with oral involvement was associated with a significant response of the oral manifestations at 12 weeks. CLINICAL RELEVANCE The oral mucosa of SR-cGVHD patients is likely to improve after 4 and 12 weeks of ruxolitinib treatment. Symptom severity at baseline does not affect the response of the oral mucosa.
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6.
Caphosol Tolerability in Oral Mucositis Patients Induced by Bone Marrow Transplantation
Chirravur, P., Sroussi, H., Villa, A.
Oral diseases. 2022
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7.
Immunohistopathology of Oral Mucosal Chronic Graft-versus-Host Disease Severity and Duration
Tollemar, V., Ström, J., Tudzarovski, N., Häbel, H., Garming Legert, K., Heymann, R., Warfvinge, G., Le Blanc, K., Sugars, R. V.
Oral diseases. 2022
Abstract
OBJECTIVE Chronic graft-versus-host disease (cGVHD) is the main cause of late non-relapse mortality following hematopoietic cell transplantation. Oral mucosal (om-) cGVHD is common but diagnosis and assessment rely on clinical interpretation and patient-reported symptoms. We investigated immune-histopathological profiles with respect to om-cGVHD severity disease duration. MATERIAL AND METHODS 94 transplant-patients and 15 healthy controls (n=212 biopsies) were investigated by quantitative immunohistochemistry for T-cells (CD4, CD8, CD5), B-cells (CD19 and CD20), macrophages (CD68) and Langerhans cells (CD1a). RESULTS We found significant increases of T- (CD4, CD8) and monocytic (CD68) cells in om-cGVHD, and a notable absence of B- (CD19 and CD20) cells. Histopathological activity correlated with increased CD4, CD8 and CD68. However, CD4 was associated with mild om-cGVHD, whereas CD8 and CD68 were found elevated in severe om-cGVHD. CD8 and CD68 levels were raised at disease onset but during late phase, the predominant CD68 population was accompanied by CD4. CONCLUSION Oral cGVHD is a heterogenous clinical disorder but our knowledge of the underlying biology remains limited. We highlight the importance of CD4, CD8 and CD68 immune profiling, together with histological grading for the staging of oral cGVHD, to broaden our understanding of the biology and individual disease course.
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8.
Long-Term Analysis of Resilience of the Oral Microbiome in Allogeneic Stem Cell Transplant Recipients
Laheij, Amga, Rozema, F. R., Brennan, M. T., von Bültzingslöwen, I., van Leeuwen, S. J. M., Potting, C., Huysmans, Mdnjm, Hazenberg, M. D., Brandt, B. W., Zaura, E., et al
Microorganisms. 2022;10(4)
Abstract
Stem cell transplantation (SCT) is associated with oral microbial dysbiosis. However, long-term longitudinal data are lacking. Therefore, this study aimed to longitudinally assess the oral microbiome in SCT patients and to determine if changes are associated with oral mucositis and oral chronic graft-versus-host disease. Fifty allogeneic SCT recipients treated in two Dutch university hospitals were prospectively followed, starting at pre-SCT, weekly during hospitalization, and at 3, 6, 12, and 18 months after SCT. Oral rinsing samples were taken, and oral mucositis (WHO score) and oral chronic graft-versus-host disease (NIH score) were assessed. The oral microbiome diversity (Shannon index) and composition significantly changed after SCT and returned to pre-treatment levels from 3 months after SCT. Oral mucositis was associated with a more pronounced decrease in microbial diversity and with several disease-associated genera, such as Mycobacterium, Staphylococcus, and Enterococcus. On the other hand, microbiome diversity and composition were not associated with oral chronic graft-versus-host disease. To conclude, dysbiosis of the oral microbiome occurred directly after SCT but recovered after 3 months. Diversity and composition were related to oral mucositis but not to oral chronic graft-versus-host disease.
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9.
Commensal oral microbiota impacts ulcerative oral mucositis clinical course in allogeneic stem cell transplant recipients
Bruno, J. S., Heidrich, V., Knebel, F. H., de Molla, V. C., Parahyba, C. J., Miranda-Silva, W., F. Asprino P, Tucunduva, L., Rocha, V., Novis, Y., et al
Scientific reports. 2022;12(1):17527
Abstract
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.
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10.
Dental Biofilm Microbiota Dysbiosis Is Associated With the Risk of Acute Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation
Heidrich, V., Bruno, J. S., Knebel, F. H., de Molla, V. C., Miranda-Silva, W., Asprino, P. F., Tucunduva, L., Rocha, V., Novis, Y., Arrais-Rodrigues, C., et al
Frontiers in immunology. 2021;12:692225
Abstract
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.