Mucositis In Children Research Articles

Topical Morphine for Oral Mucositis in Children: Dose Finding and Absorption

ContextSystemic opioids for painful chemotherapy-induced oral mucositis in children often result in unsatisfactory pain relief and a high frequency of side effects. Opioids applied topically can produce analgesia by binding to opioid receptors on peripheral terminals of sensory neurons. These receptors are upregulated during inflammation, for example, in oral mucositis. ObjectivesThe aims of this study were to investigate the dose-response relationship (n=7) and the potential absorption of topical morphine (n=5) across oral mucosa in children with oral mucositis. MethodsThe dose-response study was conducted according to a sequential study design (Dixon's Up-and-Down method) for topical morphine doses of 0.025–0.400mg/kg, with the decrease in oral pain score as the primary outcome. To assess potential absorption across oral mucosa after a single dose of topical morphine of 0.050mg/kg, blood samples were drawn and the plasma concentrations of morphine and metabolites were determined by high-pressure liquid chromatography. ResultsA decrease in oral pain score of ≥36% was achieved in six of seven patients in the dose-response part of the study. Plasma concentrations of morphine and metabolites were well below effective analgesic levels. ConclusionNo obvious dose-response effect was found for topical morphine doses of 0.025–0.400mg/kg, and topically applied morphine was not absorbed in clinically relevant doses. However, this study was limited by the small number of patients and the allowance of a systemic opioid as rescue medication. Thus, randomized controlled studies are needed to further investigate the analgesic properties of topical morphine.

Oral Mucositis in Children with Acute Lymphoblastic Leukemia

There are many types of cancers in children that are very different from those found in adults: leukaemia, lymphoma, and brain tumours are rather common in children. Acute lymphoblastic leukaemia (ALL) is the most common type of malignancy encountered. The role of pediatric dentist is very important before, during and after therapy: up to 24% of life-threatening infections arise from oral sites and areas. Early dental intervention and preventions procedures may significantly reduce oral complications associated with myelosuppressive cancer treatment. It is really important to evaluate the oral health surveys and to cut out potential sources of infection in mouth in these patients concurrent with their medical therapy. The aim of this review is summarizing the main features of oral mucositis in Childhood Acute Lymphoblastic Leukaemia, providing a little review for the approach, diagnosis and treatment of oral mucositis of ALL, which is frequent and potentially dangerous: it's important considering oral lesions of this type of childhood cancer in order to prevent complications before, during and after chemo or radio therapy to improve the quality of life of little patients.

Traumeel S in preventing and treating mucositis in young patients undergoing SCT: a report of the Children's Oncology Group

Mucositis can be a serious complication of hematopoietic SCT (HSCT). A previous phase II trial in 32 children undergoing HSCT reported a beneficial effect of the homeopathic remedy Traumeel S. The Children's Oncology Group sought to replicate the results in a multi-institutional trial. The study was an international multi-center, double-blind, randomized trial comparing Traumeel with placebo in patients aged 3-25 years undergoing myeloablative HSCT. Traumeel/placebo was started on Day -1 as a five-time daily mouth rinse. Efficacy of the treatment was assessed using the modified Walsh scale for mucositis, scored daily from Day -1 to 20 days after HCST. The main outcome was the sum of Walsh scale scores (area-under-the-curve (AUC)) over this period. Other outcomes included narcotic use, days of total parenteral feeding, days of nasogastric feeding and adverse events. In 181 evaluable patients, there was no statistical difference in mucositis (AUC) in the Traumeel group (76.7) compared with placebo (67.3) (P=0.13). There was a trend towards less narcotic usage in the Traumeel patients. No statistically beneficial effect from Traumeel was demonstrated for mucositis. We could not confirm that Traumeel is an effective treatment for mucositis in children undergoing HSCT.

Oral mucositis in children suffering from acute lymphoblastic leukaemia

Aim of the studyOral mucositis is the most commonly reported side effect observed in neoplastic patients treated with chemotherapy and radiotherapy of the head and neck region as well as in patients who have received a haematopoietic stem cell transplant. The aim of the study was to assess the oral mucosa status in children with acute lymphoblastic leukaemia (ALL) during antineoplastic therapy.Material and methodsThe clinical examination included 78 children aged 2-18 with ALL. The clinical examination was conducted using the dental preset tray. The condition of the oral mucosa was determined using the WHO scale for oral mucositis.ResultsIn the first period of antineoplastic therapy the pathological lesions of the oral mucosa of the mucositis type were observed among the examined patients. The lesions had various levels of intensity. Pain was found to be the primary symptom of oral mucositis. In this study the following were observed: local erythema of the oral mucosa in 35%, white pseudomembranous lesions in 18%, erosions in 40% and oral ulcerative lesions in 4% of patients who underwent the antineoplastic therapy. Oral mucositis was observed in 3.17% of children after 6 months of chemotherapy.ConclusionLocal treatment of oral mucositis with polyantibiotic-antifungal mixture, supporting antifungal systemic treatment, and improving the overall peripheral blood conditions in children suffering from acute lymphoblastic leukaemia improve the condition of the oral mucosa.

DNA repair gene XPD and XRCC1 polymorphisms and the risk of febrile neutropenia and mucositis in children with leukemia and lymphoma

The aim of the study is to investigate association between DNA repair gene XPD and XRCC1 polymorphisms and febrile neutropenia (FN) and mucositis. The study population consisted of 29 children with Burkitt lymphoma and 61 children with acute lymphoblastic leukemia. Analysis revealed that XRCC1194Trp allele showed a protective effect against longer FN and mucositis. There was also statistically increased risk for severe mucositis in patients with XRCC1Arg399Gln polymorphism. There are no studies that have examined this relationship before. Further studies with larger cohorts are needed to clarify the association.

Psychometric properties of the Oral Mucositis Daily Questionnaire for child self-report and importance of mucositis in children treated with chemotherapy

The objectives of this study were to examine the psychometric properties of the self-report Oral Mucositis Daily Questionnaire (OMDQ) and to measure the importance of mucositis in children receiving intensive chemotherapy. Children ≥ 12 years of age receiving intensive chemotherapy for leukemia/lymphoma or undergoing stem cell transplantation were asked to complete the OMDQ daily for 21 days after chemotherapy. Other measures of mucositis obtained concurrently with OMDQ included the World Health Organization (WHO) mucositis scale, the pain visual analog scale (VAS), and the Functional Assessment of Cancer Therapy Esophageal Cancer Sub-scale (FACT-ECS). The importance of mucositis was estimated using a VAS, time trade-off technique, and willingness to pay to avoid mucositis. Fifteen children participated. Test-retest reliability demonstrated at least moderate correlation for all questions within the OMDQ. Assessment of construct validity of the OMDQ revealed at least moderate correlation with WHO, VAS, and FACT-ECS for questions regarding pain, swallowing, drinking, and eating. Effect on sleeping and talking had lower correlations than that expected a priori. The diarrhea question of the OMDQ did not correlate with other measures of mucositis. Severe mucositis is important to children, while mild mucositis is less important to them. Children were willing to pay moderate amounts of money to prevent mucositis. The OMDQ exhibits test-retest reliability, and most questions show construct validity with the exceptions of the sleep, talking, and diarrhea questions. Therefore, the OMDQ should not be used unmodified as a self-report instrument in children with cancer. Severe mucositis is of importance to these children.

Pain management in 100 episodes of severe mucositis in children

We aimed to review the pain management in 100 episodes of severe mucositis in children and determine the incidence of associated side effects. Mucositis is a painful, debilitating condition affecting the alimentary mucosa and occurs following many anticancer treatments. Severe pain associated with mucositis may necessitate reductions, delays or termination of anticancer therapy and so intravenous morphine, preferably by patient-controlled analgesia (PCA) is the treatment of choice. Retrospective review of consecutive episodes of mucositis in children requiring intravenous opioid analgesia over a 3-year period (May 2006-April 2009). In 24/92 (26%) of cases, morphine PCA provided insufficient pain relief and children required adjuvant ketamine therapy. These children had rapidly increasing morphine requirements approaching 1000 mcg/kg/day by day 2 (more than double compared with children on morphine alone), were more likely to be female, and tended to be older (median [IQR] age 12 [6-12] years vs 7 [3-14] years). The addition of ketamine to the morphine PCA appears to be associated with reduced morphine consumption, improved pain scores, causing minimal side effects and no hallucinations. Children with severe mucositis who have escalating morphine requirements may benefit from the addition of ketamine to their morphine PCA.

Beneficial microbes for premature infants, and children with malignancy undergoing chemotherapy

This review reports the beneficial effects, observed in our clinical studies, of Bifidobacterium breve for premature infants, and children with cancers undergoing chemotherapy. To investigate the protective effects of B. breve (M-16V) as a probiotic on necrotizing enterocolitis (NEC) and infection in premature infants, we carried out a clinical study in 338 very low birth weight infants over a five-year period. These patients were supplemented with B. breve starting several hours after birth (Bifido group). 226 premature infants served as controls. Infants of the Bifido group were administered B. breve in a daily dose of 1×10(9) cells/day. The incidence of NEC was significantly reduced in the Bifido group (nil) compared with that in controls (6 cases, P<0.01). Infection also decreased significantly. Thus, administration of B. breve as a probiotic looks to be a very effective treatment for preventing NEC and infection in preterm infants. Mucositis, also referred to as mucosal barrier injury, is one of the most debilitating side effects of chemotherapy treatment. To evaluate the effects of the administration of B. breve (BBG-01, another strain than that used in the study of premature infants), a clinical study was performed to ascertain whether it attenuated intestinal mucositis in children with cancers on chemotherapy. A placebo-controlled trial was performed in patients with malignancies admitted for chemotherapy (n=42), who were randomised into two groups receiving probiotic or placebo. The frequency of fever and the use of intravenous antibiotics were significantly lower in the Bifido group than the placebo group. The B. breve administration enhanced the colonisation of anaerobes. Disruption of the intestinal microbiota after chemotherapy, such as the increase in the population levels of Enterobacteriaceae, was more pronounced in the placebo group. In conclusion, these data suggest that administration of B. breve is an effective approach to attenuating chemotherapy-induced mucositis in children with cancers. The study results strongly suggest that B. breve administration as a probiotic is an effective therapy for the prevention of NEC and infection in premature infants, and also a promising treatment for attenuating chemotherapy-induced mucositis in children with cancers.

Designing an oral mucositis assessment instrument for use in children: generating items using a nominal group technique

There was a need to develop a mucositis instrument that would be specific for use with children. This paper describes the step of generating items in the process of developing a new instrument for the assessment of oral mucositis in children. Nine health care professionals with expertise in pediatric cancer, mucositis assessment, and oral assessment in children were invited to participate in a nominal group technique to generate items that should be included in an instrument. Thirty items were generated initially. Voting processes established that six of these items were thought to be necessary for inclusion: (1) presence of ulcers, (2) pain assessment, (3) amount of pain medication received, (4) effect on eating, (5) drooling-pooling of saliva, and (6) effect on drinking. Using these six items, an initial draft of an instrument was developed that could be used to assess oral mucositis in children, namely, the Children's International Mucositis Evaluation Scale. The six items generated by this process provided the basis for a simple, feasible, and reliable instrument. With increased clinical research investigating interventions to reduce and prevent oral mucositis, such an instrument will be critical to the effective conduct of this research in children. Further testing of this instrument is necessary.

Challenges of mucositis assessment in children: Expert opinion

Mucositis is a challenging treatment-related complication in children receiving therapy for cancer. The conduct of clinical trials that investigate mucositis prevention and treatment requires adequate evaluation of the oral cavity. However, few instruments to measure mucositis in children have been appropriately developed or evaluated. A focus group of nine health care professionals with expertise in mucositis assessment, oral assessment in children and paediatric cancer aimed to determine the challenges and possible solutions to mucositis assessment in children. The results led to the identification of several areas of concern that included: (1) challenges in oral assessment in children related to age and cooperation, (2) the need for proxy responses while recognizing the challenges of reporting pain and function attributed to oral mucositis, (3) the need for an instrument that is simple, quick to complete, and easy to use in almost all children and (4) educational considerations. The results provide a basis from which guidelines for the oral assessment of mucositis in children can begin. This information could be used to aid in the development of a new scale for the assessment of oral mucositis in children.

Gum chewing as an adjunct to use of medications

Gum chewing as an adjunct to use of medications

Establishing Literature-Based Items for an Oral Mucositis Assessment Tool in Children

Although there are numerous instruments for oral mucositis (OM) assessment in adults, there is a lack of validated instruments for use in children. The objectives of this systematic review were to describe literature-based items that should be considered for a pediatric mucositis scale and other issues that should be considered when assessing mucositis in children. Literature search of PubMed and bibliography searches identified articles relevant to the assessment of mucositis and mucositis assessment studies in children. The elements established from the literature were grouped under objective, subjective, and functional items. Other issues that require consideration include the conditions for the assessment of the oral cavity and the etiology of OM. The resultant list included 23 items that have been used in mucositis assessment scales. This list of items may be used as an initial step in developing a new pediatric OM scale that particularly focuses on the unique issues in children.

Risk factors for oral mucositis in children undergoing chemotherapy: A matched case-control study

Oral mucositis (OM) is the most frequent and severe complication of chemotherapy for children with cancer, yet little is known about its risk factors. The aim of this study was to determine the risk factors associated with chemotherapy-induced OM in children. A matched case-control design was used. The matching criteria were age, type of cancer and chemotherapy regimen. Patient-and treatment-related data were collected via chart review. Conditional logistic regression analyses were performed to estimate odds ratios (OR) and adjusted odds ratios (AOR) for the development of OM. Fifty-one cases and 51 controls were identified. The mean+/-SD age of the children was 7.6+/-5.2 years, with 65 (63.73%) boys. Eighty-two percent of the children had been diagnosed with haematological malignancies (n=84). The most common chemotherapy regimen was a combination of plant alkaloids and antitumor antibiotics (n=42, 41.18%). In the multivariable model, lower body weight (AOR=0.91; 95% CI=0.84-0.98; p=0.013), lower value of log nadir neutrophil count (AOR=0.33; 95% CI=0.16-0.68; p=0.0025), and higher value of peak creatinine (AOR=1.06; 95% CI=1.01-1.12; p=0.025) were significantly associated with a greater risk of OM. Our findings suggest that children who are neutropenic, those with serum creatinine elevation, and those with a low body weight prior to chemotherapy are at greater risk of developing OM.

Association of plasma methotrexate, neutropenia, hepatic dysfunction, nausea/vomiting and oral mucositis in children with cancer

Oral mucositis is a major toxicity associated with high-dose methotrexate (HD-MTX) therapy in the treatment of children with acute lymphoblastic leukaemia and osteosarcoma. This pilot matched case-control study investigated the associations between plasma concentration of MTX at 42 (p-MTX(42h)) and 66 (p-MTX(66h)) h, absolute neutrophil count (ANC) < or = or >1.0 x 10(9)/l, serum transaminases (ASAT/ALAT) < or > or =58 U/l, WHO < or > or =grade 2 nausea/vomiting and WHO < or > or =grade 2 oral mucositis. In this study, 11 children with WHO > or =grade 2 oral mucositis were compared with 17 control children matched for age, diagnosis and MTX-dosage. The results indicated that children with p-MTX(42h) > or = 1.0 micromol/l had an odds ratio (OR) of 4.3 of developing oral mucositis when compared with the referent group of children who had p-MTX(42h) < 1.0 micromol/l. Children with p-MTX(66h) >= 0.2 micromol/l had an OR of 8.2 of developing oral mucositis when compared with the referent group of children who had p-MTX(66h) < 0.2 micromol/l. Children with ANC < or = 1.0 x 10(9)/l had an OR of 1.2 of developing oral mucositis when compared with the referent group of children who had ANC > 1.0 x 10(9)/l. In comparison with the referent group of children, who had <58 U/l ASAT/ALAT, those with ASAT/ALAT > or = 58 U/l had an OR of 1.2 of developing oral mucositis. Finally, children with WHO grade > or =2 nausea/vomiting had an elevated risk of developing oral mucositis when compared with the referent group of children who had WHO grade <2 nausea/vomiting (OR = 8.7). In conclusion, the results in this preliminary study provide support for the hypothesis that the risk of oral mucositis is associated with the plasma MTX concentration at 66 h and the level of nausea/vomiting.

Measurement of oral mucositis in children: a review of the literature

The assessment of oral mucositis is important. There is a paucity of validated oral mucositis assessment instruments for use in children. This paper reviews the available mucositis measurement tools and their applicability to a paediatric population. Literature search of PUBMED and bibliography searches identified articles relevant to mucositis measurement tools and the measurement of mucositis in paediatrics. The relevant issues in the literature could be grouped into three categories: (1) development and evaluation of oral assessment tools, (2) oral assessment in the paediatric population, and (3) challenges to the assessment of oral mucositis in children. There were numerous validated mucositis assessment scales for use in adults. Only three of these scales have received limited evaluation for use in the paediatric population. The unique challenges presented by the paediatric population are excluded from much of the discussion in the literature. The paper demonstrates the need to consider the issues specific to children. It must be determined whether previously developed tools are ideally suited for children enrolled on mucositis clinical trials.

Debridement could be a solution to promote healing of established oral mucositis in children

The aim of the study was to present a novel approach to promote healing of established oral mucositis and to alleviate symptom clusters in a group of children who were on induction chemotherapy. A clinical prospective study. Children (40) diagnosed with Grade 3 or 4 oral mucositis were randomly assigned into two groups: In Group I (n=20), accumulated debris on ulcerations was removed (debridement); In Group II (n=20), subjects had no debridement. The condition of oral lesions, speech, lips, teeth, saliva, gingiva, and swallowing ability were examined 3 x week during the study. All subjects received the same oral care regimen. They were well balanced in respect of age, the type of antineoplastic treatment, and the number. Debridement promoted resolution and decreased the severity of oral mucositis significantly. Thus, the subjects had less oral discomfort, pain, and nutritional difficulties. The data were entered in the SPSS 13.0 program, and the tests used were Kolmogorov-Smirnov, Shapiro-Wilk, Mann-Whitney, and Spearman's correlation coefficient with a 5% significance level. Well-controlled, prospective clinical studies related to the management of established oral mucositis will lead to the development of potential interventions and improved patient care.

The Effectiveness of Vitamin "E" in the Treatment of Oral Mucositis in Children Receiving Chemotherapy

The aim of this study was to study the effect of vitamin "E" in the treatment of oral mucositis. 80 patients with oral mucositis were randomly distributed into 2 groups: group A, topically applied vitamin "E" and group B, vitamin "E" was given systemically. The 2 groups were evaluated for 5 days. Results showed that in group A grades of oral mucositis improved significantly, while in group B no significant improvement was noticed. It is concluded that topical application of 100 mg vitamin "E" twice daily is an effective measure for the treatment of chemotherapy-induced oral mucositis.

Serial controlled N-of-1 trials of topical vitamin E as prophylaxis for chemotherapy-induced oral mucositis in paediatric patients

The objectives were (1) to determine whether in children undergoing doxorubicin-containing chemotherapy, topical vitamin E decreases an objective measurement of oral mucositis compared to placebo, and (2) to assess the feasibility of an innovative trial design in paediatric cancer, combining N-of-1 trials using Bayesian meta-analysis. We conducted a series of N-of-1, double-blinded, randomised controlled trials in children ⩾ 6 years of age receiving repeated cycles of identical doxorubicin-containing chemotherapy. Each study cycle was followed by topical vitamin E (800 mg) or placebo. We enroled 16 children and 45 post chemotherapy cycles were randomised to vitamin E ( N = 22) or placebo ( N = 23). There was no difference in objective mucositis scores with a mean score of 0.2 with vitamin E and 0.3 with placebo. Topical vitamin E does not reduce doxorubicin-induced oral mucositis in children. The use of N-of-1 studies and Bayesian meta-analysis may facilitate the study of some therapies in paediatric oncology.

Influence of low‐energy laser in the prevention of oral mucositis in children with cancer receiving chemotherapy

This study assessed the use of low-energy laser in the prevention or reduction of the severity of oral mucositis. A randomized clinical trial was carried out. Patients from 3 to 18 years of age treated with chemotherapy or hematopoietic stem-cell transplantation between May, 2003 and February, 2005 were eligible. The intervention group received laser application for 5 days following the start of chemotherapy. The grade of oral mucositis was assessed by the WHO per NCI-CTC common toxicity criteria and the assessments were made on days 1, 8 and 15 by a trained examiner blind to the intervention. Sixty patients were evaluable for analysis; thirty-nine (65%) were males, 35 (58%) patients had a diagnosis of leukemia or lymphoma, and 25 (42%) had solid tumors. The mean age was 8.7 +/- 4.3 years. Twenty-nine patients were randomized in the laser group and 31 in the control group. On day 1, no patients presented with mucositis. On day 8, of 20 patients (36%) who developed mucositis, 13 of them were from the laser group and 7 from the control group. On day 15, of 24 patients (41%) who developed mucositis, 13 of them were from the laser group and 11 from the control group. There was no significant difference between groups concerning the grades of mucositis on day 8 (P = 0.234) or on day 15 (P = 0.208). This study showed no evidence of benefit from the prophylactic use of low-energy laser in children and adolescents with cancer treated with chemotherapy when optimal dental and oral care was provided.

Multicenter Randomized Trial of Chewing Gum For Preventing Oral Mucositis in Children Receiving Chemotherapy

The properties of saliva led us to hypothesize that the salivary flow increase induced by gum chewing might protect the oral mucosa from lesions due to cancer chemotherapy. We conducted a multicenter randomized trial to evaluate the efficacy of chewing gum in preventing oral mucositis in 145 children receiving chemotherapy regimens expected to induce WHO grade 3-4 oral mucositis in at least 30% of patients. Patients were allocated at random to standard oral care with or without 5 gum pieces per day. No overall reduction in severe oral mucositis occurred in the gum arm (51%) compared with the standard arm (44%). VIDE, COPADM, and multidrug intensive chemotherapy caused severe oral mucositis in 75% of patients in both arms. In patients receiving less toxic regimens, a decrease in WHO grade 1-4 oral mucositis was noted in the gum arm compared with the standard arm (49% vs. 72%, P=0.03). In the multivariate analysis, the risk of oral mucositis was related only to the type of chemotherapy regimen, suggesting that further strategies for preventing oral mucositis could be mainly based on these criteria.