Chemotherapy-induced Oral Mucositis In Patients Research Articles

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

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).

Elemental diet directly affects chemotherapy-induced dermatitis and raw wound areas.

Elental® is an L-glutamine-rich elemental diet (ED) that has been widely used in Japan as a nutritional supplement for malnourished patients. In addition, Elental® has been successfully used in the management of chemotherapy-induced mucositis in cancer patients. Recently, it was also reported that Elental® can effectively reduce chemotherapy-induced oral mucositis in patients with oral squamous cell carcinoma, and can also reduce mucositis and dermatitis in animal models. However, it is unclear whether oral intake or topical application of Elental® can act directly on chemotherapy-induced oral mucositis or dermatitis. The aim of the present study was to investigate the possible direct healing effect of Elental® on chemotherapy-induced dermatitis and raw wound areas in a mouse model. Dermatitis and raw wounds were induced in nude mice by administration of 5-fluorouracil (5-FU) (via gastric tube) and mechanical injury (using a metal brush or a surgical knife). We then compared the outcome following oral or topical application of Elental® in these mice. The effect of Elental® on the growth and migration ability of the human oral keratinocyte cell line, HOK, was also examined using MTT and migration assays, respectively. In the mouse model, both oral administration and topical application of Elental® reduced 5-FU-induced dermatitis and healed raw wound areas more effectively compared with the topical application of saline. The MTT assay revealed that Elental® exerted a growth-promoting effect on HOKs. In addition, Elental® enhanced the ability of HOKs to migrate, as demonstrated by the migration assay. These findings demonstrated that the topical application as well as the oral intake of Elental® exerted a direct healing effect on chemotherapy-induced dermatitis or raw wound areas. The data also indicated that oral intake of an ED may exert a direct healing effect on chemotherapy-induced oral mucositis.

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

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.

Nigella sativa Oil Mouth Rinse Improves Chemotherapy-Induced Oral Mucositis in Patients with Acute Myeloid Leukemia

Objective The present study aims at evaluating the beneficial effect of Nigella sativa (NS) oil mouth rinse in the management of chemotherapy- (CT-) induced oral mucositis (OM) in patients with acute myeloid leukemia (AML). Methods Fifty-four AML patients were participated in this study and randomly allocated to either the test group or a control group. The patients of the test group received NS oil mouth rinse during 28-day CT, while the participants of the control group received a “magic mouthwash” formula. The primary outcome of this study was the incidence and severity of CT-induced OM in terms of erythema and ulcer. The secondary outcomes were the pain severity score, swallowing function, and the salivary concentrations of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). Results NS oil mouth rinse attenuated the progression of CT-induced OM compared with the control formula (AUC = 5.9 vs. 38.4, P < 0.05) and significantly decreased the erythema and ulceration scores (AUC of total OMAS = 11.4 vs. 85.9, P < 0.001) compared with the magic mouthwash formula. It also reduced the pain score and enabled all the participants of this group to consume normal food during treatment. It significantly decreased salivary IL-6 (AUC = 7376 vs. 16599, P < 0.001), while the changes of TNF-α levels were not significant (AUC = 676.9 vs. 885.2, P > 0.05). Conclusions NS oil mouth rinse is effective in attenuating the severity of CT-induced OM and improves the pain and swallowing function in AML patients.

Strong association between herpes simplex virus-1 and chemotherapy-induced oral mucositis in patients with hematologic malignancies.

Background/AimsA link between oral cavity infections and chemotherapy-induced oral mucositis (CIOM) in patients with hematological malignancies (HMs) undergoing intensive chemotherapy (IC) or hematopoietic stem cell transplantation (HSCT) has been suggested. However, conclusive data are lacking, and there are no current guidelines for the prophylactic use of antimicrobials to prevent CIOM in these populations.MethodsThe relationships between herpes simplex virus (HSV) reactivation and Candida colonization in the oral cavity and CIOM in patients with HMs undergoing IC or HSCT were evaluated. Patients aged ≥ 19 years with HMs undergoing IC or HSCT were enrolled. Each patient was evaluated for HSV and Candida in the oral cavity along with CIOM at baseline and during the 2nd, 3rd, and 4th weeks.ResultsSeventy presentations among 56 patients were analyzed. CIOM was observed in 23 presentations (32.9%), with a higher incidence associated with HSCT (17 of 35 presentations, 48.6%) than with IC (six of 35 presentations, 8.6%). The reactivation of HSV-1 was significantly associated with an increased incidence of CIOM after adjusting for age, sex, type of disease, and treatment stage. A higher HSV-1 viral load was associated with an increased incidence of CIOM. The presence of Candida was not associated with CIOM.ConclusionsHSV-1 reactivation in the oral cavity was highly associated with CIOM in patients with HMs undergoing high-dose chemotherapy.

Evaluation of an oral care protocol on prevention and treatment of chemotherapy-induced oral mucositis in patients with hematological neoplasms

Objective To determine the effectiveness of an oral care protocol on prevention and treatment of chemotherapy-induced oral mucositis in patients with hematological neoplasms. Methods Totally 106 patients with hematological neoplasms undergoing therapies from March to October 2017 were enrolled. Patients who were included from March to June 2017 constituted the control group, others from July to October constituted the intervention group. Patients in control group received the regular care, while patients in intervention group received a 3-week period oral care protocol. The oral health status of the patients was recorded and compared between the two groups. Results On the 7th,14th, 21th day after chemotherapy, the oral mucositis level of I degree,Ⅱdegree, Ⅲdegree and Ⅳ degree of the intervention group were 11, 13, 17, 1 cases, 28, 16, 0, 0 cases,9, 3, 0, 0 cases, which were lower than the control group whose degrees were 24, 18, 10, 2 cases, 21, 13, 12, 0 cases, 13, 9, 8, 0 cases, respectively. The difference between the two groups was statistically significant (Z=-2.177,-2.504,-2.113, P <0.05). On the 3th, 7th, 14th and 21th day after chemotherapy, the oral pain scores reported by patients in the intervention group were 2.00(2.50), 3.00(2.75), 2.50(2.00), 0.00(1.00), which were lower than the control group whose scores, in contrast, were 3.00(4.00), 5.00(3.25), 5.50(4.00), 2.00(3.25). The difference between the two groups was statistically significant (Z=-2.587,-3.326,-4.925,-3.217, P <0.05). The positive rate of microbial examination in the intervention group was 14.6%(7/48), which was lower than 36.2%(21/58) in the control group. The difference between the two groups was statistically significant(χ2=6.318, P<0.05). Conclusions The oral care protocol established and implemented based on evidence could effectively decrease the incidence of chemotherapy-induced oral mucositis, ease oral pain and reduce inflammation for patients with hematological neoplasms. Key words: Hematological neoplasms; Oral mucositis; Oral care protocol

The Effect of Orally-Administered Zinc in the Prevention of Chemotherapy-Induced Oral Mucositis in Patients with Acute Myeloid Leukemia

BackgroundOral mucositis is a frequent yet serious adverse event associated with chemotherapy in acute myeloid leukemia. Although a wide spectrum of drugs has been tested for prophylaxis of oral mucositis, few of them are satisfactory. There is currently substantial clinical interest in zinc (Zn) as an antioxidant and a protective agent against chemotherapy -relatednormal tissue injury. Therefore, in the present study, we investigated whether zinc prevents oral mucositis associated with chemotherapy in patients with AML.MethodsA total of 140patients with AML were randomly selected and divided into two groups where the case groups received zinc sulfate 220 mg orally and the control groups received placeboes 3 times a day during their chemotherapy course. Data were analyzed by SPSS version 15 software. Mann-Whitney U test was used to evaluate mucositis, and pain intensity.ResultsThe incidence rates of mucositis were all markedly lower in oral zinc sulfate group than in control (P = 0.004).ConclusionsZinc is available for preventing the complications of oral mucositis, and thus for improving patient quality of life.

Association of tumor necrosis factor-α polymorphism with chemotherapy-induced oral mucositis in patients with esophageal cancer.

The purpose of this study was to evaluate the association between tumor necrosis factor (TNF)-α polymorphisms and oral mucositis (OM) from 5-fluorouracil (5-FU) plus cisplatin (CDDP) chemotherapy for esophageal cancer. The rs1799964 polymorphism of TNF-α was genotyped using the tetra-primer amplification refractory mutation system polymerase chain reaction. The experimental group comprised 64 patients who received chemotherapy for esophageal cancer between 1997 and 2004; a total of 106 patients between 2005 and 2013 were investigated as the validation group. Univariate analysis of the experimental group revealed that the TT genotype of TNF-α rs1799964 was significantly higher in patients with grade 1-4 OM compared with the TC/CC genotypes [univariate odds ratio (OR)=4.0; P=0.029]. Similarly, univariate analysis of the validation group revealed that the percentage of the TT genotype was significantly higher in patients with grade 1-4 OM compared with the TC/CC genotypes (OR=2.8; P=0.043). This difference in risk was replicated in the validation cohort. Thus, the TT genotype of TNF-α rs1799964 may be a predictor of chemotherapy-induced OM in patients with esophageal cancer.

The Effects of Oral Cryotherapy on Chemotherapy-Induced Oral Mucositis in Patients Undergoing Autologous Transplantation of Blood Stem Cells: A Clinical Trial.

BackgroundOral mucositis is one of the irritating side effects of chemotherapy in patients undergoing bone marrow transplantation. However, up until now, the common methods of oral mucositis therapy have failed to show significant effects.ObjectivesThe aim of this study was to investigate the effects of local cryotherapy on the intensity of chemotherapy-induced oral mucositis in autologous bone marrow transplantation patients.Patients and MethodsIn this single, blinded, randomized clinical trial, 29 patients undergoing stem cell transplantation in Iran were selected by convenience sampling, and randomly allocated to control (n = 13) and intervention groups (n = 16). In the intervention group, cryotherapy was applied, while the control group received a normal saline mouthwash. The severity of the mucositis and neutrophil rate were investigated in five periods, based on the world health organization (WHO) scales. The data were analyzed using descriptive statistics, the Mann-Whitney test, repeated measures analysis of variance (ANOVA), and linear regression.ResultsIn both groups, the mucositis reached its peak intensity on the 7th day, and the least intensity was obtained on the 21st day. The neutrophil rate reached the minimum value on the 7th day, then increased up to the 21st day. The two groups showed no significant differences between the mucositis severity on the 14th and 21st days (P = 0.164), while the severity of the mucositis in the cryotherapy group was significantly less than that in the saline mouthwash group (1.81 < 2.54 and 0.13 < 0.92, respectively) on the 7th and 14th days (P < 0.05). There was no significant difference in the neutrophil rate between the groups.ConclusionsThe results showed that cryotherapy is more effective than the saline mouthwash in reducing the severity of mucositis. This method is recommended for the prevention of mucositis in bone marrow transplantation.

Preventive effects of amino-acid-rich elemental diet Elental® on chemotherapy-induced oral mucositis in patients with colorectal cancer: a prospective pilot study.

PurposeThe prospective pilot study was designed to evaluate the preventive effects of amino-acid-rich elemental diet (ED), Elental®, on chemotherapy-induced oral mucositis in patients with colorectal cancer. The factors influencing its efficacy are also investigated.MethodsA total of 22 eligible patients with colorectal cancer experiencing grade 1–3 oral mucositis during treatment with fluorouracil-based chemotherapy entered the current study. Their average age was 67 years. There were 10 male and 12 female. The PS was 0 in the majority of patients. Patients received two courses of the same chemotherapy regimen and Elental® concurrently after recovery to grade 0 or 1 oral mucositis.ResultsFOLFOX6 + bevacizumab in 8 patients, FOLFIRI + bevacizumab in 8 patients, FOLFIRI + panitumumab in 1 patient, FOLFIRI in 1 patient, XELOX + bevacizumab in 2 patients, and S-1 + cetuximab in 2 patients were used as first-line (16 cases) or as second-line (6 cases) chemotherapy. Dose reduction of 5-fluorouracil (5-FU) or oral fluoropyrimidine was performed in the 2 patients achieving grade 3 oral mucositis and in the 3 patients achieving grade 2 oral mucositis. The maximum grade of oral mucositis decreased in 18 of the 22 patients during the first treatment course with Elental® (p = 0.0002) and in 20 of the 22 patients in the second course (p < 0.0001). Multivariate analyses found that the dose reduction in 5-FU or oral fluoropyrimidine, ED intake, and the prior administration of ED were each a significant factor for the preventive efficacy on oral mucositis.ConclusionThe amino-acid-rich elemental diet Elental® may be useful as a countermeasure for 5-FU-based chemotherapy-induced oral mucositis in patients with colorectal cancer.

LB003-MON: The Effect of Dietary Glutamine Supplementation on Chemotherapy-Induced Oral Mucositis in Patients with Esophagogastric Cancer

multidisciplinary nutrition intervention project at a major urban general hospital in Hanoi. Methods: Cross-sectional data from patients aged 31 d 90 y hospitalized in seven key wards were obtained using a one-day survey method in 2010 and repeated in 2013. Data included age, sex, admission type, route of feeding, days of hospitalization, actual or recall weight and height, and nutrition Subjective Global Assessment (SGA) scores. Unavailable patientsand those expected to be discharged within 24 hours were excluded. Malnutrition was defined based on WHO references. Kappa and logistic regression analyses were performed. Results: The 2010 and 2013 samples consisted of 674 (57% male) and 791 (58% male) patients. At baseline, 18% (19/106) children were wasted, 13% (14/106) stunted, 4% (4/106) overweight and 0% obese, while 33% (179/536) adults were underweight, 5% (29/536) overweight and 1% (4/536) obese. Using SGA at baseline, 48% (52/108) children and 50% (268/542) adults were at nutrition risk (Fair agreement, Kappa 0.21 [0.06 0.35], p < 0.01). Inpatients in 2013 vs. 2010 differed by admission type, weight documentation, and feeding route (P< 0.05). After adjusting for potential confounding variables including sex, age, missing actual weight (or height), and days of hospitalization, patients admitted in 2013 vs. 2010 were 23% less likely to be malnourished (OR: 0.77 [0.61 0.98]). Using this adjusted model, the hazard ratio of malnutrition in children <5 y was 75% lower (OR: 0.25 [0.13 0.49]) and 2.6 times higher in adults 19 24.9 y (OR: 2.57[1.62 4.10]) compared to adults age 25 65 y. Conclusion: The risk of malnutrition in a major Vietnamese general hospital improved over a three-year period of nutrition intervention and was highest in young adults. Prospective studies are needed.

The effect of the low-level laser on prevention of chemotherapy-induced oral mucositis in patients with acute leukemia

Statement of Problem: Low-level laser has been shown to be beneficial in reducing significantly chemotherapy-induced mucositis. However, the approach has not gained wide acceptance, so far. Purpose: The aim of this study was to evaluate the effect of low-level laser therapy clinically in prevention of chemotherapy-induced oral mucositis in patients suffering acute hematologic cancers. Materials and Methods: 40 patients who aged 12 and older, who had acute myeloid / lymphoid leukemia and were receiving myeloablative chemotherapy regimen were included. Patients were randomly divided into the control and the experiment groups. A diode laser (Aluminum Gallium Indium; Azor-2k-02, Russia, λ = 660 nm, power: 25 mw, spot size: 2 mm, continuous mode, Energy: 1.5 J per point) was applied on 12 points for one month, twice weekly. Results: Based on the WHO scales, In the fourth session, the people suffering from mucositis were increased to 18 people, 12 of which were in the control group. This increasing trend has been also observed in NCI scales, so that in the fourth session, the number of people suffering from mucositis reached to 12 persons and the severity and degree of leisure reached to 3, 4. Conclusion: Low level laser could reduce the severity and the pain of the mucositis.

The impact of oral herpes simplex virus infection and candidiasis on chemotherapy-induced oral mucositis among patients with hematological malignancies

The aim of this study was to evaluate the influences of oral candidiasis and herpes simplex virus 1 (HSV-1) infections in chemotherapy-induced oral mucositis (OM). The medical records of 424 consecutive patients with hematological malignancies who had received chemotherapy at a medical center in Taiwan from January 2006 to November 2007 were retrospectively reviewed. The results of swab cultures of fungus and HSV-1 for OM were correlated with associated clinical features. Younger age, myeloid malignancies, and disease status other than complete remission before chemotherapy were significantly correlated with the development of OM. Risks of fever (p < 0.001) and bacteremia were higher in patients with OM. Among 467 episodes of OM with both swab cultures available, 221 were non-infection (47.3%) and 246 were related to either fungal infections, HSV-1 infections, or both (52.7%); of the 246 episodes, 102 were associated with fungal infections alone (21.8%), 98 with HSV-1 infections alone (21%), and 46 with both infections (9.9%). Patients who had received antifungal agents prior to OM occurrence tended to have HSV-1 infection (p < 0.001). Our results suggest that Candida albicans and HSV-1 play an important role in chemotherapy-induced OM in patients with hematological malignancies.