Severe Mucositis Research Articles

Oral health related quality of life in head and neck cancer survivors within the first year following treatment: a cross-sectional study in Karachi, Pakistan

After completing treatment for head and neck cancer (HNC), patients often face oral complications like oral pain, limited mouth opening and dry mouth which significantly reduce their oral health related quality of life (OHRQoL). These issues impact their overall well-being, social activities and long-term survival. The primary objective of this study was to evaluate OHRQoL and its association with sociodemographic characteristics, oral hygiene practices and oral clinical parameters such as oral hygiene status and oral mucositis grade in patients who have completed treatment for head and neck cancer. This cross-sectional study involved 79 HNC-treated patients within first year after completion of cancer treatment attending ENT and dental clinics at outpatient department (OPD) setting in Karachi. Data was collected electronically using structured questionnaire comprising of EORTC QLQ H&N – 35 to measure OHRQoL, patients were also examined for oral hygiene status using oral hygiene index- simplified (OHI-s) and oral mucositis grade using WHO oral mucositis scale. Multiple linear regression was used to test OHRQoL associations with the sociodemographic and different clinical factors. The result showed an overall mean score for oral health related quality of life (OHRQoL) of 25.02 ± 15.86 (95% CI 21.46–28.57), with difficulty in mouth opening 53.16 ± 18.88 and dry mouth 45.14 ± 24.48 being predominant concerns for decline in the OHRQoL in the population. Male predilection was observed among participants n = 60 (75.9%), majority of the participants n = 41 (51.9%) were below 52 years of age. n = 63 (80%) participants received radiotherapy alongside surgery and chemotherapy. Most of participants n = 66 (83.5%) experienced moderate to severe oral mucositis with poor oral hygiene status n = 56 (71%). Significant associations were found between OHRQoL and BMI, OH status, marital status, monthly income, gender and fluoride toothpaste (p < 0.05). These findings suggest that Quality of Life (QoL) among HNC treated patients is negatively impacted by their poor oral health, post cancer treatment. Therefore, it is important to evaluate and modify the current treatment modalities and involve multidisciplinary teams, to improve their OHRQoL thereby enhancing overall QoL.

Predicting severe radiation-induced oral mucositis in head and neck cancer patients using integrated baseline CT radiomic, dosimetry, and clinical features: A machine learning approach

PurposeTo establish the early prediction models of radiation-induced oral mucositis (RIOM) based on baseline CT-based radiomic features (RFs), dosimetric data, and clinical features by machine learning models for head and neck cancer (HNC) patients. MethodsIn this single-center prospective study, 49 HNCs treated with curative intensity modulated radiotherapy (IMRT) were enrolled. Baseline CT images (i.e., CT simulation), dosimetric, and clinical features were collected. RIOM was assessed using CTCAE v.5.0. RFs were extracted from manually-contoured oral mucosa structures. Minimum-redundancy-maximum-relevance (mRMR) method was applied to select the most informative radiomics, dosimetric, and clinical features. Then, binary prediction models were constructed for predicting acute RIOM based on the top mRMR-ranked radiomics, dosimetric, and clinical features alone or in combination, using random forest classifier algorithm. The predictive performance of models was assessed using the area under the receiver operating curve (AUC), accuracy, weighted-average based sensitivity, precision, and F1-measure. ResultsAmong extracted features, the top 10 RFs, the top 5 dose-volume features, and the top 5 clinical features were selected using mRMR method. The model exploiting the integrated features (10-radiomics + 5-dosimetric + 5-clinical) achieved the best prediction with AUC, accuracy, sensitivity, precision, and F1-measure values of 91.7 %, 90.0 %, 83.0 % 100.0 %, and 91.0 %, respectively. The model developed using baseline CT RFs alone provided the best performance compared to dose-volume features or clinical features alone, with an AUC of 87.0 %. ConclusionOur results suggest that the integration of baseline CT radiomic features with dosimetric and clinical features showed promising potential to improve the performance of machine learning models in early prediction of RIOM. The ultimate goal is to personalize radiotherapy for HNC patients.

Efficacy of photobiomodulation therapy in the management of oral mucositis in patients with head and neck cancer: A systematic review and meta-analysis of randomized controlled trials.

Numerous studies have examined the effectiveness of photobiomodulation therapy (PBMT) in reducing chemoradiotherapy (CRT)-induced oral mucositis (OM) in patients with head and neck cancer (HNC). Despite this, there is an urgent need to update the meta-analyses on this topic. This meta-analysis aims to explore the impact of PBMT on CRT-induced OM in these patients. We conducted a systematic search in PubMed, Embase, Cochrane, LILACS, and Web of Science from January 2000 to October 2023. This search focused on randomized controlled trials (RCTs) that assessed the effects of PBMT on CRT-induced OM. The study included a total of 14 RCTs encompassing 869 patients with HNC. The incidence of OM in the PBMT group was significantly lower from the second week onwards compared to the control group (RR = 0.49, CI = 0.25-0.97, I2 = 71%, p = 0.04), and this was present until the seventh week (RR = 0.77, CI = 0.61-0.99, I2 = 89%, p = 0.04). Furthermore, the occurrence of severe mucositis in the PBMT group decreased from the third week (RR = 0.51, CI = 0.29-0.90, I2 = 12%, p = 0.02) until the conclusion of the intervention (RR = 0.45, CI = 0.24-0.85, I2 = 80%, p = 0.01). Additionally, PBMT showed beneficial effects in alleviating OM-related pain (WMD = -1.09, 95% CI = -1.38 to -0.880, I2 = 13%, p < 0.00001). The use of He-Ne or InGaAlP lasers with a power range of 10-25 mW demonstrated the most favorable outcomes in preventing and treating OM. PBMT has shown considerable efficacy in reducing the incidence, severity, and pain associated with OM in patients with HNC. Future studies are encouraged to further investigate the most effective parameters for PBMT in the management of OM.

A QUASI-EXPERIMENTAL STUDY TO ASSESS THE EFFECTIVENESS OF TOPICAL APPLICATION OF HONEY ON ORAL MUCOSITIS AMONG HEAD AND NECK CANCER PATIENTS UNDERGOING RADIATION THERAPY IN TERTIARY CARE HOSPITAL OF AMRITSAR, PUNJAB.

Cancer is the leading cause of death around the world. Radiation therapy is made to kill growing cancer cells but certain normal cells get effected too, this damage to normal cell cause side effects of radiation therapy. The most debilitating side effect is radiation induced Oral Mucositis. This is major concern for attention, so there is need to provide conventional therapies to head and neck cancer patients to reduce the severity of oral mucositis. A Quasi-experimental study was conducted to assess the effectiveness of topical application of honey among 60 head and neck cancer patients undergoing radiation therapy at Sri Guru Ram Dass Institute of Medical Science and Research, Vallah, Amritsar, Punjab. Purposive sampling technique was used to collect data. The data wa

P11 A Rare and Serious Cause of “Blueberry Muffin Syndrome”

Abstract Urgent dermatology review was sought for a neonate born at term via emergency caesarean section for reduced movements. The pregnancy was complicated by gestational diabetes and infection with suspected coxsackie virus in the second trimester. There were 15 purple/blue nodules consistent with “blueberry muffin syndrome” and associated anaemia (118 g/L). Due to hypoxia, she was given antibiotics for suspected sepsis. TORCH screen was negative and USS abdomen and cranium were normal. A blood film showed B cell aplasia and LDH was raised (710 unit/L). CXR showed a mediastinal mass, left pleural effusion and left lung opacity. A skin biopsy was taken, chest drain placed and the baby transferred to Great Ormond Street. She was subsequently diagnosed with acute myeloid leukaemia following bone marrow and lumbar puncture. All three skin biopsies showed a malignant infiltrate with one displaying positivity for CD12 and CD33. CT and MRI scans have shown widespread nodules in the lungs, liver, kidneys, bones and intra-cranially. She is being treated with chemotherapy which has been complicated by a cardiac arrest and severe mucositis leading to colostomy. She is also NG fed and has sensorineural hearing loss. The nodules seen in “blueberry muffin syndrome” are most commonly extramedullary erythropoiesis but can also represent purpura or metastases. The causes are congenital infections, blood disorders or tumours. There is frequently associated anaemia (as in our case) and hepatosplenomegaly. This case demonstrates a rare and concerning cause of the syndrome and highlights the role dermatologists can play in diagnosis.

Honey in Alleviating Severe Oral Mucositis Among Head and Neck Cancer Patients Undergoing Radiation Therapy.

Aiming to resolve debates on honey's efficacy for radiotherapy-induced severe oral mucositis in head and neck cancer, we conducted a meta-analysis focused on randomized trials, primarily assessing severe mucositis incidence. Secondary outcomes included weight loss, pain management, and honey types. A comprehensive literature search was conducted in PubMed, Embase, WOS, and the Cochrane Library up to December 2023. The analysis concentrated on randomized controlled trials that assessed the efficacy of honey, targeting the incidence of mucositis as the main outcome. Additional outcomes explored were weight loss, intolerable pain, and the specific types of honey used in interventions. Data analysis was performed using CMA software, and a funnel plot was employed to identify publication bias. The analysis of 176 records resulted in the inclusion of 10 studies with 599 patients receiving radiotherapy. The research showed that honey significantly reduced the occurrence of grade 3-4 mucositis (severe mucositis), provided significant pain relief, and had a positive effect on reducing weight loss. Regarding the type of honey used, no significant differences were found in their effectiveness in alleviating severe mucositis. Honey serves as an effective intervention for individuals with oral mucositis. It can be considered as an adjuvant in the management of clinical radiotherapy-associated oral mucositis, particularly for patients requiring prolonged use of anti-analgesic or antifungal medications.

Acute myeloid leukemia with central nervous system involvement successfully treated with gilteritinib

A 69-year-old woman was referred to our hospital due to hyperleukocytosis. We diagnosed acute myeloid leukemia and started induction therapy with the CAG regimen (aclarubicin, cytarabine and filgrastim). However, the patient was refractory to the initial treatment and developed quadriplegia, and a cerebrospinal fluid (CSF) test showed elevated blasts. We then performed intrathecal chemotherapy, and the number of blasts in CSF gradually decreased. But only two cycles of intrathecal therapy were possible due to severe methotrexate-induced mucositis. The leukemia cells had fms-like kinase 3-internal tandem duplication (FLT3-ITD), so we started treatment with oral gilteritinib. The patient then achieved hematological complete remission. Her paralysis was also resolving, and the CSF was clear of blasts for more than 6 months. Some reports show that gilteritinib may penetrate the CNS, and this case also supports the effectiveness of gilteritinib on CNS leukemia.

Ablation of Intestinal Epithelial Sialylation Predisposes to Acute and Chronic Intestinal Inflammation in Mice

BACKGROUND & AIMSAddition of sialic acids (sialylation) to glycoconjugates is a common capping step of glycosylation. Our study aims to determine the roles of the overall sialylation in intestinal mucosal homeostasis. METHODSMice with constitutive deletion of intestinal epithelial sialylation (IEC Slc35a1–/– mice) and mice with inducible deletion of sialylation in intestinal epithelium (TM-IEC Slc35a1–/– mice) were generated, which were used to determine the roles of overall sialylation in intestinal mucosal homeostasis by ex vivo and muti-omics studies. RESULTSIEC Slc35a1–/– mice developed mild spontaneous microbiota-dependent colitis. Additionally, 30% of IEC Slc35a1–/– mice had spontaneous tumors in the rectum over the age of 12 months. TM-IEC Slc35a1–/– mice were highly susceptible to acute inflammation induced by 1% DSS vs controls. Loss of total sialylation was associated with reduced mucus thickness on fecal sections and within colon tissues. TM-IEC Slc35a1–/– mice showed altered microbiota with an increase in Clostridia disporicum, which is associated a global reduction in the abundance of at least 20 unique taxa; however, metabolomic analysis did not show any significant differences in short-chain fatty acid levels. Treatment with 5-fluorouracil (5-FU) led to more severe small intestine mucositis in the IEC Slc35a1–/– mice vs. WT littermates, which was associated with reduced Lgr5+ cell representation in small intestinal crypts in IEC Slc35a1-/-;Lgr5-GFP mice. CONCLUSIONSLoss of overall sialylation impairs mucus stability and the stem cell niche leading to microbiota-dependent spontaneous colitis and tumorigenesis.

Prevalence and risk factors of chemotherapy-induced oral mucositis among adult cancer patients at the cancer unit of Mbarara Regional Referral Hospital.

Chemotherapy is a common treatment for cancer, but it is associated with adverse drug reactions like oral mucositis. This condition destroys basal cells in the oral mucosal layer, causing inflammation and ulceration. This can impact the patient's physical, emotional, and psychological well-being, affecting treatment outcomes and quality of life. This study aims to determine the prevalence, severity, and risk factors of chemotherapy-induced oral mucositis among adult cancer patients. The study was a cross-sectional study conducted among adult cancer patients receiving chemotherapy at the cancer unit of Mbarara Regional Referral Hospital in southwestern Uganda. Data was collected through patient interviews, oral examinations, and patient chart reviews. Out of 268 patients, 115 (42.9%) experienced oral mucositis. Grade 2 oral mucositis was the most common (44.3%) followed by grade 1 (35.7%) and grade 3 (20.0%). Independent risk factors of chemotherapy-induced oral mucositis were female gender (Adjusted Odds Ratio (AOR)=2.19, 95% confidence interval [CI]: 1.27-3.78; p-value=0.005), poor oral hygiene (AOR=3.70, 95% CI: 1.51-9.10; p-value=0.04), and receiving chemotherapy containing an alkylating agent (AOR=3.17, 95% CI: 1.63-6.19; p-value<0.001). The study found that two out of five chemotherapy patients developed oral mucositis, with nearly half being grade 2. The risk factors identified in our study were comparable to those reported in previous studies. Therefore, identification and assessment of cancer patients at high risk for chemotherapy-induced oral mucositis should be routinely done for proper and timely management.

Influence of anxiety/depression on chemotherapy-induced oral mucositis and related quality of life: A prospective cohort study

ObjectiveThe impact of anxiety and depression on chemotherapy-induced oral mucositis has not been extensively explored in the literature. The aim of the present study was to evaluate anxiety/depressive symptoms, health-related quality of life, and oral health-related quality of life and their association with oral mucositis among individuals receiving chemotherapy. MethodsThis is a prospective longitudinal study carried out at a Brazilian referral service. The Hospital Anxiety and Depression Scale (HADS), World Health Organization Quality of Life-BREF (WHOQOL-BREF), and Oral Health Impact Profile questionnaire (OHIP-14) were applied at D0 (before chemotherapy) and D15 of chemotherapy. Clinicodemographic data and oral mucositis severity scores were evaluated. ResultsA total of 37 individuals (median age: 49 years) were included in the study. Nearly 38% of patients developed chemotherapy-induced oral mucositis and had higher anxiety/depression scores at baseline. Oral mucositis had a negative impact on oral health-related quality of life regarding functional limitation, physical pain, physical disability, and handicap. ConclusionAnxiety/depressive symptoms are associated with oral mucositis that affects overall health and oral health-related quality of life.

Adherence of Candida Species Isolated from Patients with Head and Neck Cancer Presented for Radiation Therapy and its Correlation with Hemogram

The objective of the current study was to quantify the adherence property of Candida species causing infections in head and neck cancer patients on radiation therapy (RT) or chemoradiotherapy (CRT). Additionally, the study aimed to establish a correlation between adherence properties and patients’ hemograms. A prospective cohort study was done on head and neck cancer (HNC) patients with oropharyngeal candidiasis. All patients received radiation doses ranging from 60 to 70 Gy using Intensity Modulated Radiation Therapy. Inoperable patients received concurrent chemotherapy with cisplatin 40mg/m2 once weekly during the course of RT. Swabs were collected from patients with signs and symptoms of candidiasis and microbiological confirmation and speciation were done according to standard protocol. An in vitro adherence test was done. Hemogram of all the patients at the start of infection was compared with the adherence. Candidiasis was detected in 58(35.3%) out of a total of 164 patients (Age 36-85). Candida albicans was the most prevalent 39(67.2%) species isolated. C.albicans showed the highest adherence which was statistically significant. The hemogram at the start of treatment and with C. albicans infection showed a statistically significant decrease in the absolute lymphocyte count (p-value 0.0001), RBC count (p-value 0.004) and haemoglobin level (p-value 0.003). Less adherence was seen with non-albicans Candida infection when compared to C.albicans (Odds 0.894, 95% CI -0.818-0.977), significant at 5 % (0.013). C. albicans showed significant adherence, which indicates the severity of infection. The occurrence of oral candidiasis is strongly associated with low lymphocyte count and severity of mucositis. Absolute lymphocyte count needs to be monitored in HNC patients who are undergoing RT or CRT.

Effect of Pre-Transplantation Nutritional Status on the Early Related Complications of Allogeneic Hematopoietic Stem Cell Transplantation:a Cohort Study

Background Allogeneic hematopoietic stem cell transplantation is an effective method for the treatment of hematologic malignancies. Malnutrition is a common complication and has a negative impact on poor prognosis. It has been proved that blood biochemical indexes such as muscle mass ratio albumin etc. can reflect earlier the nutritional status of patients, but the influence of muscle mass pre-transplantation on the early transplantation related complications remains unclear. Objective To investigate the effect of pre-transplantation skeletal muscle mass (SMM) on the early outcome of allogeneic hematopoietic stem cell transplantation, and to provide clinical evidence for nutritional intervention and prognosis improvement. Method A cohort study was conducted in 77 patients with leukemia who received allogeneic hematopoietic stem cell transplantation in the Hematology Medical Center of Chongqing Xinqiao Hospital from January to October 2022 were selected. The skeletal muscle quality was evaluated by bioelectrical impedance method. According to the skeletal muscle mass, the patients were divided into normal skeletal muscle mass group(36) and low skeletal muscle mass group(41). The baseline data of the patients were collected, including personal information and clinical data. SPSS23.0 software was used to compare the differences in oral mucositis, digestive tract symptoms, infection and hematopoietic reconstitution time between the two groups. Result Before transplantation, the SMM of patients was poor, which was not up to the normal value in 53.25%.The incidence of oral mucitis in normal SMM group was 41.67%, significantly lower than that in low SMM group 92.68%( χ2=23.255, P&amp;lt;0.001).The severity of oral mucositis was significantly different (Z=6.461, P&amp;lt;0.001) between the normal SMM group and the low SMM group. The incidence of hypoalbuminemia in normal SMM group was 16.67%, significantly lower than that in low SMM group 46.34%( χ2=7.699， P&amp;lt;0.001).The incidence of overt gastrointestinal bleeding and infection in normal SMM group were significantly lower than those in low SMM group ( c ２=4.208， P=0.040； c ２=4.727， P=0.030). the neutrophils and platelets grafting time in the normal SMM group was significantly shorter than that in the low SMM group ( Z=2.943， P=0.003； Z=2.756， P=0.006). There was no significant difference in the incidence of diarrhea, nausea and vomiting, stomachache/ abdominal pain between the two groups. Conclusion The incidence of low skeletal muscle mass is high in patients before transplantation, and low skeletal muscle mass is associated with the onset of oral mucositis, the severity of oral mucositis, hypoalbuminemia,gastrointestinal bleeding ,infectionand the delay of neutrophil and platelet implantation time in patients at the early stage of transplantation. Patients should actively improve skeletal muscle mass before transplantation to improve the early outcome of transplantation.

Clinical Outcomes of Patients Receiving 3 Versus 4 Doses of Methotrexate with Concomitant Anti-Thymocyte Globulin; A Single Center Experience

Background: Four doses of methotrexate (MTX) given on day +1, +3, +6, and +11 after allogeneic stem cell transplant (HSCT) is considered one of the most common graft-versus-host disease (GVHD) prophylaxis regimen. However, mucositis and occasionally transaminitis prohibit safe delivery of the fourth dose of MTX. Prior single institution studies showed conflicting results comparing the outcomes of patients who received 3 vs 4 doses of MTX but to our knowledge, the effect of concomitant anti-thymocyte globulin (ATG) use has not been reported. As both ATG and MTX synergistically prevent GVHD via suppressive effects on T-cells. Our institution uniquely incorporates ATG as part of the conditioning regimen for patients receiving HSCT from 10/10 loci match unrelated donors (MUD) and here we report the clinical outcomes between patients who received 3 versus (vs) 4 doses of MTX. Methods: We retrospectively reviewed the charts of patients who underwent HSCT from MUD between 2009 to 2023 at the University of Iowa Hospital and Clinics. We use rabbit ATG (Thymoglobulin R), given at 0.5 mg/kg on day -3, 2 mg/kg on day -2, and 2.5 mg/kg on day -1. MTX is given at 15 mg/m 2 on day +1 and 10 mg/m 2 on day +3, +6 and +11 per institutional protocol. Statistical Analysis: Time was calculated from transplant to recurrence or death for recurrence-free survival (RFS) and overall survival (OS), respectively. For acute and chronic GVHD (aGVHD and cGVHD), time was calculated from transplant to onset of acute and chronic GVHD. Relapse and death were considered as competing events. For non-relapse mortality (NRM), time was calculated from transplant to death; relapse was considered a competing event. Cox regression and Fine-Gray competing risk models were used to estimate the effect of patient, disease, and treatment characteristics on outcomes Results: We identified 296 patients with various indications of HSCT; the most common was acute myeloid leukemia (45.3%). There were 117 and 179 patients who received 3 doses and 4 doses of MTX respectively. Patients characteristics reported in table 1. Median follow-up was 21.9 months (range 0.6 to 150.8). Patients who received 4 doses of MTX were more frequently male (68.2% vs 49.6%, p&amp;lt;0.01), received a reduced intensity (compared to myeloablative) preparative regimen (38.0% vs 23.1%, p&amp;lt;0.01), were older (median 58 vs 54 years, p=0.01), and underwent transplant at an earlier year (median year of transplant 2014 vs 2018, p&amp;lt;0.01). Severe mucositis was the most common reason for omission of the 4 th dose of MTX. Maximum grade of aGVHD was similar between cohorts (p=0.83). A statistically significant difference was not evidenced between patients receiving 4 versus 3 doses of MTX for the following outcomes: aGVHD (HR 1.11, 95% CI 0.84-1.46), grade 3-4 aGVHD (HR 1.41, 95% CI 0.77-2.60), RFS (HR 1.01, 95% CI 0.66-1.56), NRM (HR 1.33, 95% CI 0.84-2.10) and OS (HR 1.21, 95% CI 0.87-1.69). While significant on univariate analysis, MTX dose was not significantly associated with extensive cGVHD (HR 1.44, 95% CI 0.92-2.26) after adjustment for transplant year. Additionally, the median time to neutrophil engraftment was 14 days in both cohorts. Conclusion: When ATG is used concomitantly, omission of the 4 th dose of MTX does not significantly impact the rate of neutrophil engraftment, cumulative incidence of aGVHD, cGVHD, RFS, NRM, and OS after HSCT from MUD. However, a small sample size and non-randomized nature of this study prompts further confirmation study from a large prospective multicenter randomized control trial.

Early Initiation of Ketamine Infusion for Pain Management in Pediatric BMT Patients with Mucositis

Background: As many as 90% of children undergoing hematopoietic stem cell transplant (HSCT) will experience painful mucositis. The mainstay of treatment for these children has been opioid analgesia which can be associated with sedation and respiratory depression. Additionally, these children may experience heightened opioid tolerance and physiologic dependence contributing to lengthy admissions. Ketamine is an anesthetic and analgesic which has been used successfully in conjunction with opioids in the treatment of painful mucositis. This study aimed to reduce total opioid use per day by 10% and overall pain scores by 2 in pediatric patients with mucositis undergoing HSCT through initiation of ketamine at the same time as an opioid patient-controlled analgesia (PCA). Methods: Beginning April 2022, HSCT patients (both autologous and allogeneic) at Children's Hospital Colorado were started on ketamine infusion in conjunction with an opioid PCA for management of painful mucositis. Mucositis severity and duration, opioid consumption, pain and functional scores, time of initiation of ketamine therapy, ketamine side effects, and duration of PCA and ketamine therapy were recorded for a retrospective (April 2021- March 2022, n=6) and a prospective cohort (April 2022- April 2023, n=17). A 2-sample-T-test was used to calculate the difference in mean cumulative opioid use per day and the mean 24-hour average pain scores between the retrospective and prospective groups. Results: 71% of children in the prospective group underwent ketamine initiation alongside an opioid PCA. Patients in this group had a 46% reduction in mean cumulative opioid use per day (CI 1.265-2.318, p=0.000). Reduction in 24-hour pain scores between the retrospective and prospective groups was 1.18, failing to meet our goal of 2.0. However, there was still a statistically significant difference in mean scores (CI 0.499-1.860, p=0.001). Additionally, this intervention was tolerated well and only 1 patient (16%) was intolerant of ketamine side effects in the prospective cohort. Conclusions: Initiation of ketamine alongside an opioid PCA for the treatment of mucositis pain is safe and significantly reduces cumulative opioid exposure and 24-hour pain scores in children undergoing HSCT.

Differences in Observed Toxicities for Adolescent and Young Adult Patients with Aggressive Mature B-Cell Lymphomas Treated at Adult Versus Pediatric Cancer Center - a Comparative Cohort Study

Introduction: Standard treatment regimens for pediatric and adult patients with mature B-cell lymphomas vary significantly. For adolescent or young adult (AYA) patients, who may be candidates for either pediatric or adult regimens, limited data are available regarding comparative toxicities and efficacy for adult versus pediatric therapies. Methods: A retrospective review was completed for individuals aged 12-39 years at diagnosis with aggressive mature B-cell lymphomas seen between 2011 to 2023 at Ohio State University Comprehensive Care Center (adult cohort) and Nationwide Children's Hospital (pediatric cohort). Diagnoses included diffuse large B cell lymphoma (DLBCL), double hit lymphoma (DHL), Burkitt lymphoma (BL), primary mediastinal B cell lymphoma (PMBCL), grey zone lymphoma (GZL), and unclassifiable high-grade B cell lymphoma (HGBCL). Progression free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method and compared by log-rank test. Differences between adult and pediatric cohort were compared using Fisher's exact test and Chi-squared test. Cox regression model was used to identify prognostic factors for PFS. Results: Among 180 eligible AYA patients, 156 were treated at the adult center and 24 at the pediatric center. The median age was 30 years (median 15 pediatric [range 12-18] and 31 adult [range 21-39; p&amp;lt;0.001]). Other characteristics included male sex in 75% of pediatric vs 65% adult patients (p=0.3), stage 4 disease in 25% vs 47%(p&amp;lt;0.001), CNS involvement in 8.3% vs 5.4% (p=0.6), and LDH &amp;gt;2x upper limit of normal in 21% vs 31% (p=0.2). The overall median follow-up was 4.8 years (4.5 vs 4.8, p=0.7). Adult center histology included DLBCL (95); DHL (9); BL (8); PMBCL (31); GZL (4); and HGBCL (9). Pediatric diagnoses were DLBCL (13); BL (8); PMBCL (2); and HGBCL (1). The most common treatments included R-CHOP (57), R-EPOCH (56), RM-CHOP (20), and R-CODOX-M/R-IVAC (16) at the adult center and CCG5961 (7), ANHL1131 (15), and ANHL0221 (1) protocols at the pediatric center. CCG5961 Group B protocol includes pre-phase, induction, and consolidation phases of COP, COPADM, and CYM. Group C includes the same pre-phase and induction, except for higher doses of MTX, with CYVE consolidation with high-dose MTX and randomization to 1 or 4 cycles of maintenance. ANHL1131 protocol was like CCG5961; major differences include randomization to receive rituximab during induction and consolidation and 2 cycles of maintenance for group C patients. ANHL0221, a PTLD protocol, involves 2 cycles of cyclophosphamide, prednisone, and rituximab followed by 4 cycles of cyclophosphamide and prednisone. A greater incidence of unplanned hospitalization (79% pediatric vs 50% adult, p=0.007), grade 3 mucositis (38% vs 12%, p=0.005), febrile neutropenia (67% vs 44%, p=0.035), and fungal infections (25% vs 3%, p&amp;lt;0.001) were observed for the pediatric cohort (Table 1). Patients in the adult cohort were more likely to receive radiation therapy (26% vs 0%, p=0.004) and experience neuropathy at last follow-up (22% v 0%, p=0.009). Among all patients, other adverse events during follow-up included diagnosis of depression/anxiety (93), heart failure (16), impaired renal function (20), and secondary malignancy (6) (Table 1). For the total population, 2-year PFS was 78% (88% pediatric vs 77% adult, p=0.35), and 2-year OS was 93% (96% vs 92%, p=0.31). For patients with DLBCL or DHL, there was a trend towards improved PFS in the pediatric versus adult cohort (p=0.06, Figure 1), and on univariable analysis a trend towards lower risk for progression with receipt of a more intensive regimen compared with R-CHOP/R-MCHOP (hazard ratio 0.46, 95% confidence interval 0.2-1.1, p=0.07). Conclusions: We observed a higher incidence of short-term adverse effects including severe mucositis, febrile neutropenia, and fungal infection, but lower rates of radiation consolidation and ongoing neuropathy in AYA patients with aggressive mature B-cell lymphoma treated with pediatric versus adult regimens. Relatively higher dose intensity (compared to adult treatments), standard use of CNS prophylaxis, and lower dosage of vinca-alkaloids likely account for the greater incidence of short-term adverse effects and lower rates of neuropathy seen in patients treated at pediatric centers. Further study is needed to evaluate differences in efficacy between treatment approaches in AYA patients with DLBCL/DHL.

Gut microbiome predicts gastrointestinal toxicity outcomes from chemoradiation therapy in patients with head and neck squamous cell carcinoma

ObjectivesChemoradiation (CRT) in patients with locally advanced head and neck squamous cell cancer (HNSCC) is associated with significant toxicities, including mucositis. The gut microbiome represents an emerging hallmark of cancer and a potentially important biomarker for CRT-related adverse events. This prospective study investigated the association between the gut microbiome composition and CRT-related toxicities in patients with HNSCC, including mucositis. Materials and methodsStool samples from patients diagnosed with locally advanced HNSCC were prospectively collected prior to CRT initiation and analyzed using shotgun metagenomic sequencing to evaluate gut microbiome composition at baseline. Concurrently, clinicopathologic data, survival outcomes and the incidence and grading of CRT-emergent adverse events were documented in all patients. ResultsA total of 52 patients were included, of whom 47 had baseline stool samples available for metagenomic analysis. Median age was 62, 83 % patients were men and 54 % had stage III-IV disease. All patients developed CRT-induced mucositis, including 42 % with severe events (i.e. CTCAE v5.0 grade ≥ 3) and 25 % who required enteral feeding. With a median follow-up of 26.5 months, patients with severe mucositis had shorter overall survival (HR = 3.3, 95 %CI 1.0–10.6; p = 0.02) and numerically shorter progression-free survival (HR = 2.8, 95 %CI, 0.8–9.6; p = 0.09). The gut microbiome beta-diversity of patients with severe mucositis differed from patients with grades 1–2 mucositis (p = 0.04), with enrichment in Mediterraneibacter (Ruminococcus gnavus) and Clostridiaceae family members, including Hungatella hathewayi. Grade 1–2 mucositis was associated with enrichment in Eubacterium rectale, Alistipes putredinis and Ruminococcaceae family members. Similar bacterial profiles were observed in patients who required enteral feeding. ConclusionPatients who developed severe mucositis had decreased survival and enrichment in specific bacteria associated with mucosal inflammation. Interestingly, these same bacteria have been linked to immune checkpoint inhibitor resistance.

Efficacy of Low-Level Laser Therapy for Oral Mucositis in Hematologic Patients Undergoing Transplantation: A Single-Arm Prospective Study.

Oral mucositis significantly affects the quality of life in hematologic cancer patients undergoing hematopoietic stem cell transplantation. Despite global evidence supporting the efficacy of low-level laser therapy (LLLT) for mucositis prevention, its clinical adoption in Japan is limited. This study aimed to fill this gap by evaluating the safety and efficacy of LLLT in a Japanese patient population. In a single-group, non-blinded, exploratory trial, we compared 21 LLLT-treated patients against a historical control of 96 patients. The primary endpoint was the incidence of Grade ≥ 2 mucositis, based on NCI-CTCAE ver. 4.0. The LLLT group showed a significantly lower incidence of Grade ≥ 2 mucositis (23.8%) compared to the control group (64.6%) (p = 0.0006). Furthermore, Grade ≥ 2 mucositis correlated with increased oral dryness and longer hospital stays. Our study confirms the efficacy of LLLT in reducing the onset of severe oral mucositis among Japanese hematologic cancer patients, advocating for its clinical introduction as a preventive measure in Japan.

Lack of association between XRCC1 SNPs and acute radiation‑induced injury or prognosis in patients with nasopharyngeal carcinoma.

The response to radiation therapy (RT) is closely associated with DNA damage repair. X-ray repair cross-complementing group-1 (XRCC1) is a key gene in the DNA damage repair pathway, and SNPs in this gene alter the expression and activity of its effector protein, which may in turn affect sensitivity to RT. Therefore, the course of tumor treatment and local control rate can be influenced. In the present study, a group of 158 patients with nasopharyngeal carcinoma (NPC) who received intensity-modulated RT at Fujian Cancer Hospital (Fuzhou, China) between July 2012 and October 2013 were included in retrospective chart review and followed up. Plasma was collected before treatment for genotype analysis of the three SNPs of XRCC1, namely Arg194Trp, Arg280His and Arg399Gln. Acute radiation-induced injuries sustained during treatment was graded according to the Radiation Therapy Oncology Group scoring criteria. Post-treatment follow-up was performed until August 2020. In the 158 cases of NPC, no statistically significant association was observed between the three SNPs of the XRCC1 gene and the severity of acute radiation-induced injury or prognosis. However, the AA genotype of XRCC1-Arg399Gln tended to be associated with worse progression-free survival (PFS) compared with the GA + GG genotype, although this was not significant (P=0.069). In addition, multivariate logistic analysis showed that nodal stage was significantly associated with the occurrence of acute severe radiation-induced oral mucositis (P=0.018), and there was also a trend towards an association between nodal stage and the incidence of acute severe radiation-induced pharyngitis; however, this was not statistically significant (P=0.061). Furthermore, multivariate Cox regression analysis showed that older age, distant metastasis and higher clinical stage were independent risk factors for PFS in patients with NPC. In conclusion, relying solely on the aforementioned SNPs of the XRCC1 gene may not provide a robust enough basis to predict the response to RT or prognosis in patients with NPC.

Markers of intestinal mucositis to predict blood stream infections at the onset of fever during treatment for childhood acute leukemia.

Despite chemotherapy-induced intestinal mucositis being a main risk factor for blood stream infections (BSIs), no studies have investigated mucositis severity to predict BSI at fever onset during acute leukemia treatment. This study prospectively evaluated intestinal mucositis severity in 85 children with acute leukemia, representing 242 febrile episodes (122 with concurrent neutropenia) by measuring plasma levels of citrulline (reflecting enterocyte loss), regenerating islet-derived-protein 3α (REG3α, an intestinal antimicrobial peptide) and CCL20 (a mucosal immune regulatory chemokine) along with the general neutrophil chemo-attractants CXCL1 and CXCL8 at fever onset. BSI was documented in 14% of all febrile episodes and in 20% of the neutropenic febrile episodes. In age-, sex-, diagnosis- and neutrophil count-adjusted analyses, decreasing citrulline levels and increasing REG3α and CCL20 levels were independently associated with increased odds of BSI (OR = 1.6, 1.5 and 1.7 per halving/doubling, all p < 0.05). Additionally, higher CXCL1 and CXCL8 levels increased the odds of BSI (OR = 1.8 and 1.7 per doubling, all p < 0.0001). All three chemokines showed improved diagnostic accuracy compared to C-reactive protein and procalcitonin. These findings underline the importance of disrupted intestinal integrity as a main risk factor for BSI and suggest that objective markers for monitoring mucositis severity may help predicting BSI at fever onset.

The Efficacy of Modified Melphalan and Busulfan-Based Conditioning Regimen for Autologous-HSCT in Low-Risk and Intermediate-Risk AML Patients

Abstract: Background: Treatment options for patients with low-risk and intermediate-risk acute myeloid leukemia (AML) patients (non-M3) who achieved complete response (CR) after one course of induction chemotherapy include consolidation chemotherapy, autologous hematopoietic stem cell transplantation (auto-HSCT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT). Compared with chemotherapy, auto-HSCT could significantly reduce relapse rate, as was associated with significantly lower transplant-related mortality compared with allo-HSCT, but relapse rate was relatively high. The selection of conditioning regimen was crucial to reduce relapse rate after transplantation. In this study, we made refinements in the conditioning regimen with two alkylating agents, namely MCBA (the combination of melphalan, cladribine, busulfan, and cytarabine). We aim to investigate the efficacy of MCBA conditioning regimen for auto-HSCT in low-risk and intermediate-risk AML patients who achieved CR after one course of induction chemotherapy. Methods: This prospective multi-center clinical trial was conducted in 5 tertiary hospitals in China, and enrolled low-risk and intermediate-risk AML patients (non-M3) who achieved CR after one course of induction chemotherapy, followed by 1-3 courses of high-dose cytarabine consolidation chemotherapy, and underwent auto-HSCT from May 2021 to June 2023 (ChiCTR Registration ID: ChiCTR2200056167). The MCBA conditioning regimen consists of melphalan 70mg/m 2/d, day -6~-5, cladribine 5mg/m 2/d, day -4~-2, busulfan 3.2mg/kg/d, day -8~-7, cytarabine 2g/m 2/d, day -4~-2. Results and Discussion: This study included a total 21 AML patients, 14 males, 7 females, with median age 41 years (ranged 20-56 years). There were 8 of low-risk and 13 of intermediate-risk. The median infused mononuclear cell and CD34+ cell counts were 12.22×10 8/kg (ranged 1.79-34.68×10 8/kg) and 2.28×10 6/kg (ranged 1.05-17.15×10 6/kg) respectively. Neutrophil and platelet engraftment were achieved in all patients, with a median time of 13 days (ranged 11-27 days) and 32 days (ranged 12-150 days) respectively. On the day of reconstitution, all patients exhibited good responses, including hematologic CR and minimal residual disease (MRD) negativity rates of 100%. 11 (52.4%) patients received maintenance therapy after auto-HSCT, with a median time of 3.5 months (ranged 1-9 months). Azacytidine, venetoclax or geritinib were the main maintenance therapies. With a median follow-up of 306 days（ranged 43-798 days）, the estimated 1-year overall survival (OS) and 1-year disease-free survival (DFS) were 80.4±13.4% and 70.9±12.8%, respectively. 4 patients relapsed within 1year, and the median time from HSCT to relapse was 240 (101-314) days. The probability of relapsed rate was 29.1±12.8%. Mucositis was the main reported regimen-related toxicity, mostly were mild and well tolerated. Severe mucositis included grade Ⅱ liver damage (4.8%), grade Ⅱ oral mucositis (4.8%) and grade Ⅲ-Ⅳ diarrhea (9.5%), respectively. Conclusion: The preliminary data demonstrated the efficiency of MCBA conditioning regimen for auto-HSCT in low-risk and intermediate-risk AML patients who achieved CR after one course of induction chemotherapy. The regimen-related toxicity was well tolerated.