Photobiomodulation minimizes taste changes during hematopoietic cell transplantation: A randomized clinical trial.

Prevention and treatment protocols for taste changes observed during hematopoietic cell transplantation (HCT) are not well-established. The purpose of this study was to assess the efficacy of photobiomodulation (PBM) in relieving taste changes and preventing lingual papillae atrophy. HCT patients received PBM (n = 42) on the tongue dorsum using an InGaAIP laser (660 nm, 100 mW, 1.1 W/cm2, 8.8 J/cm2). During the HCT conditioning (T0), severe neutropenia (T1), and after neutrophil engraftment (T2), taste acuity for sweet, bitter, sour, and salty solutions, and clinical appearance of lingual papillae were compared with those of a placebo group (n = 43). PBM significantly reduced hypogeusia, ageusia, and parageusia at T1 and T2, and also successfully prevented papillae atrophy during all the analyzed HCT periods. In conclusion, PBM enhanced taste acuity during HCT. The decrease in papillae atrophy indicated a potential regenerative effect of this therapy on tongue mucosa.

Dental consensus on HSCT - Part II: dental Care during HSCT

ABSTRACT During the state of immune vulnerability in hematopoietic stem cell transplantation (HSCT), the patient has an increased risk of developing a vast number of complications, including severe problems in the oral cavity. These situations require professional oral care to act in the diagnosis and treatment of these conditions, as well as to develop prevention protocols to minimize patient's complications. Oral mucositis, opportunistic infections, bleeding, specific microbiota, taste, and salivary alterations are complications that can occur during HSCT and interfere with various aspects, such as pain control, oral intake, nutrition, bacteremia and sepsis, days of hospitalization and morbidity. Several guidelines have been published to address the role of professional oral care during the HSCT, we describe a consensus regarding these recommendations.

Dental consensus on HSCT - Part II: dental Care during HSCT.

During the state of immune vulnerability in hematopoietic stem cell transplantation (HSCT), the patient has an increased risk of developing a vast number of complications, including severe problems in the oral cavity. These situations require professional oral care to act in the diagnosis and treatment of these conditions, as well as to develop prevention protocols to minimize patient's complications. Oral mucositis, opportunistic infections, bleeding, specific microbiota, taste, and salivary alterations are complications that can occur during HSCT and interfere with various aspects, such as pain control, oral intake, nutrition, bacteremia and sepsis, days of hospitalization and morbidity. Several guidelines have been published to address the role of professional oral care during the HSCT, we describe a consensus regarding these recommendations.

Oral ulcers and sarcoid-like reaction in lymph nodes after cemiplimab therapy for locally advanced cutaneous squamous cell carcinoma: a case report.

Cemiplimab is a novel programmed death-1 inhibitor recently approved for advanced cutaneous squamous cell carcinoma. Immune-related adverse events derived from cemiplimab are similar to other anti-PD-1 drugs, including gastrointestinal and cutaneous toxicities. Oral immune-related adverse events were not reported with cemiplimab in previous studies; thus this case report warns of the fact that the oral cavity may be a site of immune-related adverse events during programmed death-1 block therapy and that this can lead to significant limitations when not properly treated. The present report describes the case of a patient with locally advanced cutaneous squamous cell carcinoma metastatic to cervical lymph nodes who developed dysphagia due to large and painful oral ulcers after a single dose of cemiplimab. The patient also exhibited a sarcoid-like reaction in mediastinal lymph nodes. No immune-related adverse events were found in any other organs. The oral lesions showed significant improvement after topical and short-course systemic corticosteroids, and low-level laser therapy was also performed in the oral lesions. The patient achieved a near-complete response and treatment was discontinued. This article discusses in detail the clinical outcomes and oral toxicity management of cemiplimab therapy for cutaneous squamous cell carcinoma.

Oral ulcers and sarcoid-like reaction in lymph nodes after cemiplimab therapy for locally advanced cutaneous squamous cell carcinoma: a case report

ABSTRACT Cemiplimab is a novel programmed death-1 inhibitor recently approved for advanced cutaneous squamous cell carcinoma. Immune-related adverse events derived from cemiplimab are similar to other anti-PD-1 drugs, including gastrointestinal and cutaneous toxicities. Oral immune-related adverse events were not reported with cemiplimab in previous studies; thus this case report warns of the fact that the oral cavity may be a site of immune-related adverse events during programmed death-1 block therapy and that this can lead to significant limitations when not properly treated. The present report describes the case of a patient with locally advanced cutaneous squamous cell carcinoma metastatic to cervical lymph nodes who developed dysphagia due to large and painful oral ulcers after a single dose of cemiplimab. The patient also exhibited a sarcoid-like reaction in mediastinal lymph nodes. No immune-related adverse events were found in any other organs. The oral lesions showed significant improvement after topical and short-course systemic corticosteroids, and low-level laser therapy was also performed in the oral lesions. The patient achieved a near-complete response and treatment was discontinued. This article discusses in detail the clinical outcomes and oral toxicity management of cemiplimab therapy for cutaneous squamous cell carcinoma.

Salivary antioxidant enzymes associated with oral toxicity in haematopoietic cell transplantation: An observational study.

BACKGROUND: In haematopoietic cell transplantation (HCT), oral mucositis and xerostomia are related to conditioning-related oxidative stress. The role of salivary antioxidant enzymes in oral toxicity is poorly described. The aim of this study was to verify the association between salivary antioxidant enzymes and oral mucositis and xerostomia in HCT. DESIGN: Saliva from autologous and allogeneic HCT patients (n = 77) was selected before conditioning (T0), during the neutropenia period (T1) and after marrow engraftment (T2). Salivary flow, total salivary proteins, and superoxide dismutase, catalase and glutathione reductase activities were measured. RESULTS: There were no significant differences in salivary flow, total salivary proteins and catalase at the three HCT time points. Glutathione reductase levels were reduced at T1 compared to T0 (P = .013) and T2 (P = .001). Superoxide dismutase levels were increased from T0 to T2 (P = .013). Neither of these enzymes was associated with oral mucositis. Increased superoxide dismutase levels were associated with xerostomia frequency. Levels of this enzyme also showed significant correlation with days of xerostomia in T2 (ρ = .40, P = .002). CONCLUSIONS: Salivary antioxidant enzymes changed before and during early periods after HCT. The increase in salivary superoxide dismutase suggested partial activation of the salivary antioxidant system and was associated with xerostomia.

Is Salivary Busulfan the Cause of Oral Mucositis and the Changes in Salivary Antioxidant Enzymes After Hematopoietic Cell Transplantation?

BACKGROUND: To determine whether the busulfan (Bu) present in saliva during hematopoietic cell transplantation (HCT) conditioning correlates with oral mucositis and the changes in salivary antioxidant enzymes. METHODS: Bu levels in the plasma and saliva of 19 patients who received HCTs were quantified. Salivary flow and salivary superoxide dismutase and catalase activities were measured during HCT. For the toxicity analysis of salivary Bu, an in vitro assay was conducted by exposing human keratinocytes to artificial saliva containing Bu. RESULTS: Plasma and salivary Bu concentrations were very similar (rho = 0.92, P < 0.001). Salivary Bu concentration correlated with the degree of oral mucositis severity (rho = 0.391, P = 0.029) and was inversely proportional to salivary superoxide dismutase and catalase activities (rho = -0.458, P = 0.036; rho = -0.424, P = 0.043, respectively). Cells exposed to Bu-containing saliva had fewer viable cells (P < 0.01) and more apoptotic cells (P = 0.001) than those exposed to non-Bu-containing saliva. CONCLUSIONS: Bu found in saliva during HCT conditioning was correlated with severe oral mucositis and the reduction in salivary antioxidative activity. Furthermore, Bu can be toxic to keratinocytes.

Association of oral toxicity and taste changes during hematopoietic stem cell transplantation: a preliminary study.

PURPOSE: The aim of this study was to characterize the taste changes and taste bud atrophy observed in the period of neutropenia of HCT and to determine the influence of transplantation toxicity on these changes. METHODS: Autologous and allogeneic HCT patients (n = 51) were selected to perform taste acuity tests prior to conditioning (T0) and during neutropenia (T1). The frequency and time duration of oral mucositis, presence of tongue depapillation, and salivary flow rate were also evaluated. Quality of life was assessed using specific questionnaires. RESULTS: We observed a significant increase in hypogeusia (66.6%, p = 0.001) and dysgeusia (21.4%, p = 0.013) at T1, compared with T0. Bitter taste was the most altered, mainly when the patient underwent conditioning with melphalan (OR = 4.47, p = 0.049). Prolonged oral mucositis (≥ 8 days) (OR = 5.62, p = 0.039) and autologous transplantation (OR = 4.08, p = 0.033) were predictive factors for tongue depapillation. Changes in sour taste (OR = 10.70, p = 0.045) and reduced salivary flow (OR = 21.00, p = 0.013) were associated to body weight loss at T1. Taste changes significantly reduced the quality of life at T1, compared with T0. CONCLUSIONS: Frequency of hypogeusia was high in the neutropenia period of the HCT. None of the taste changes was determined by oral mucositis, tongue depapillation, or reduced salivary flow, but melphalan conditioning reduced the bitter taste sensation. Loss of body weight and poor quality of life were associated with taste changes and reduced salivary flow. Further studies are necessary to elucidate this association and the risk factors for taste changes in HCT.

Retrospective study of the digestive tract mucositis derived from myeloablative and non-myeloablative/reduced-intensity conditionings with busulfan in hematopoietic cell transplantation patient.

Busulfan is a major component of chemotherapy conditioning in hematopoietic cell transplantation (HCT). This alkylating agent is highly toxic at myeloablative doses, exposing HCT patients to risks of mortality. Non-myeloablative (NMA) and reduced-intensity conditioning (RIC) using busulfan have shown impaired toxicity. However, the toxicity of NMA/RIC in the digestive tract is poorly described. This study aimed to characterize the mucositis in the oral cavity (OM), oropharynx/esophagus, and gastrointestinal tract derived from conditionings with myeloablative and non-myeloablative doses of busulfan. We retrospectively retrieved clinical data of HCT patients (n = 100) who underwent myeloablative conditioning (MAC) or NMA/RIC with busulfan. Frequency and time duration of mucositis in the oral cavity and oropharynx/esophagus, diarrhea, and prescription of total parenteral nutrition (TPN) and opioids were also collected. OM severity (p = 0.009) and time duration of mucositis in oropharynx/esophagus (p = 0.022) were frequently higher in MAC than NMA/RIC. A myeloablative dose of busulfan was a risk factor for OM grade ≥ 2 (OR = 4.8, p = 0.002) and for mucositis in oropharynx/esophagus ≥ 5 days (OR = 2.64, p = 0.035). A longer duration of mucositis in the oropharynx/esophagus was also associated with an increase in the prescription of opioids (OR = 7.10, p < 0.001).Overall survival (OS) in MAC was significantly higher than that in NMA/RIC (p = 0.017). No variables related to mucositis interfere significantly in OS. In conclusion, myelosuppression in busulfan-based regimens are predisposed to a high risk for severe OM and to prolonged mucositis in the oropharynx/esophagus.

Análise das alterações de paladar durante o transplante de célulastronco hematopoiéticas / Analysis of taste alterations during hematopoietic cell transplantation

As alterações do paladar durante o transplante de células tronco hematopoiéticas (TCTH) são frequentemente descritas em períodos após a finalização do transplante, porém pouco se conhece sobre quais sabores e que tipo de alterações de percepção são vivenciadas pelos pacientes durante o transplante. O objetivo deste trabalho foi caracterizar as alterações do paladar e de despapilação presentes no período de neutropenia do TCTH, bem como verificar se há associação entre essas alterações e variáveis clínicas relacionadas ao transplante e à toxicidade na mucosa oral. Também se avaliou o impacto das alterações do paladar e da mucosa oral na qualidade de vida dos pacientes. Foram selecionados 52 pacientes de TCTH autólogo e alogênico, que realizaram testes de acuidade do paladar antes do condicionamento e durante a neutropenia. Os pacientes foram ainda submetidos a oroscopia para avaliação de mucosite oral e despapilação no dorso da língua. Foi também realizado inquérito quanto a xerostomia e a alterações no paladar. Foi realizado teste de acuidade na percepção dos sabores doce, amargo, azedo e salgado, ofertados em soluções contendo concentrações baixas e altas de substâncias estimuladoras desses sabores. A qualidade de vida foi avaliada pelo questionário EORTC QLQ-C30 e QLQ-H&N35. Detectou-se que os 46,1% dos pacientes exibiram alterações do paladar antes do condicionamento do TCTH, mas que essa frequência aumentou para 90,5% durante a neutropenia (teste do c2, p=0.042). O tipo de alteração mais comum foi a hipogeusia dos sabores de concentração mais forte, principalmente do amargo. Alta frequência de pacientes (72,0%) foi detectada exibindo despapilação no período de neutropenia, porém essa despapilação não foi associada às alterações de percepção de cada tipo de sabor. Não houve associação entre alterações do paladar e tipo de transplante, tipo de condicionamento e variáveis relacionadas à toxicidade na cavidade oral e no trato gastrointestinal. Houve associação significativa entre despapilação e duração da mucosite oral >=8 dias (OR= 5,62, IC95% = 0,98-60,30, p=0.039). As alterações salivares e do paladar reduziram significativamente na qualidade de vida durante a neutropenia em comparação ao período que antecedeu o condicionamento. Concluiu-se que as alterações do paladar já estão presentes antes do TCTH, mas há aumento da frequência dessas alterações, principalmente de hipogeusia. A despapilação na língua ocorreu após o condicionamento, e foi associada a maior tempo de duração da mucosite oral. O impacto das alterações salivares e do paladar na qualidade de vida do paciente durante a neutropenia é alto e devem ser minimizados mediante a adoção de estratégias mais abrangentes, que incluam manutenção da integridade da mucosa oral.