Photobiomodulation for chemotherapy-induced oral mucositis in leukemic children: A randomized controlled clinical trial.

OBJECTIVES: Evaluation of the effectiveness of Photobiomodulation(PBM) for chemotherapy-induced oral mucositis (OM) in leukemic children. MATERIALS AND METHODS: A randomized controlled clinical study including forty-four leukemic children diagnosed with chemotherapy-induced OM at the Hematology/Oncology inpatient unit at Alexandria University Children's Hospital, Alexandria, Egypt. Patients were randomly assigned to either the control or test groups with a 1:1 ratio. The control group received conventional symptomatic treatment, while the test group was treated with PBM in addition to the symptomatic treatment. The response to both treatment modalities was evaluated according to the reduction of pain and lesions severity from baseline to 5, 10, and 14 days after treatment. RESULTS: A significant reduction of pain was recorded on day 10 in the test group compared to the control group (p < 0.001). There was also a significant decline in the OM grades between the two groups on day14 (p = 0.003). No adverse events were reported. CONCLUSIONS: The use of PBM along with the conventional treatment was effective in reducing pain and in the recovery of OM lesions in children receiving chemotherapy for the treatment of ALL. It was also safe and applicable to children.

Impact of the COVID-19 pandemic on health-related quality of life and anxiety in pediatric hematology/oncology patients.

Since the World Health Organization declared the COVID-19 pandemic in March 2020, the strain on healthcare services affected patients suffering from various comorbidities and added to the psychological burden. The study aimed to assess the health-related quality of life (HRQoL) and anxiety levels of pediatric Hematology/Oncology patients during the COVID19 pandemic and evaluate the association between anxiety levels and physical, emotional, and social aspects of HRQoL. A cross-sectional study was conducted on 292 children between 2.5 - 13 years with chronic hematological/oncological disorders. Pediatric Quality of Life Generic Core Scale and Spence Children's Anxiety Scale were used for assessment of HRQoL and anxiety, respectively. Linear regression was performed to assess the association between background and COVID-19 related factors with anxiety level. Multivariate Analysis of Variance (MANOVA) was performed to assess the association between the three HRQoL dimensions with child anxiety and different independent variables. Transfusion-dependent patients had lower anxiety levels than patients receiving chemotherapy (B=-14.45, 95% CI=-21.94,-6.95).Children who were aware of the pandemic had lower anxiety scores than those who were not, while those suffering from canceled clinic days had higher anxiety levels (B=-8.66,95% CI=-14.86,-2.45, and B = 7.33,95% CI =1.22,13.45, respectively). Anxiety significantly reduced the three HRQoL domains (B=-0.36, 95% CI=-0.47, -0.24 for physical functioning, B=-0.45, 95% CI =-0.56, -0.33 for social functioning and B=-0.50, 95% CI=-0.63,-0.38 for emotional functioning). This study highlights the effect of the pandemic on the anxiety level and hence the HRQoL of chronic hematological/oncological pediatric patients for guiding policies and interventions to maintain their psychological well-being.

Clinical Characteristics and Outcomes of 101 Children with Hemophagocytic Lymphohistiocytosis: A Four-Year Single-Center Experience from Egypt.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition, arising either due to genetic mutations or from a variety of underlying diseases. This prospective observational study reports the clinical and laboratory data as well as the outcome of pediatric HLH in Egypt. HLH was diagnosed according to the Histiocyte Society HLH-2004 diagnostic criteria conducted at Alexandria University Children's Hospital over four years. One-hundred-one patients were enrolled (44 males and 57 females), and the median age at presentation was 13.1 months (range: 1 day - 181.4 months). Almost 75% of the patients had consanguineous parents, and one-third had a history of an affected family member (HLH or HLH-like illness). The median time interval between the first HLH symptom and diagnosis was 34 days. At diagnosis, patients were preliminarily classified as having primary HLH in 61% of patients and secondary HLH in 39% of patients. The diagnosis was confirmed genetically in 57 patients. Seventy-eight percent of patients received the HLH-94 and HLH-2004 protocols, only seven patients have undergone hematopoietic stem cell transplantation. The overall survival was 26.4% by the end of the study; the most common cause of death was uncontrolled disease activity. This descriptive study, on a large cohort of pediatric HLH in Africa and the Middle East, sheds some light on the epidemiological characteristics of HLH patients and the available diagnostic and therapeutic tools. The mortality rate was considerably high, highlighting the importance of early diagnosis and initiation of appropriate therapy.

Neuroinflammatory Disease as an Isolated Manifestation of Hemophagocytic Lymphohistiocytosis.

Isolated neuroinflammatory disease has been described in case reports of familial hemophagocytic lymphohistiocytosis (FHL), but the clinical spectrum of disease manifestations, response to therapy and prognosis remain poorly defined. We combined an international survey with a literature search to identify FHL patients with (i) initial presentation with isolated neurological symptoms; (ii) absence of cytopenia and splenomegaly at presentation; and (iii) systemic HLH features no earlier than 3 months after neurological presentation. Thirty-eight (20 unreported) patients were identified with initial diagnoses including acute demyelinating encephalopathy, leukoencephalopathy, CNS vasculitis, multiple sclerosis, and encephalitis. Median age at presentation was 6.5 years, most commonly with ataxia/gait disturbance (75%) and seizures (53%). Diffuse multifocal white matter changes (79%) and cerebellar involvement (61%) were common MRI findings. CSF cell count and protein were increased in 22/29 and 15/29 patients, respectively. Fourteen patients progressed to systemic inflammatory disease fulfilling HLH-2004 criteria at a mean of 36.9 months after initial neurological presentation. Mutations were detected in PRF1 in 23 patients (61%), RAB27A in 10 (26%), UNC13D in 3 (8%), LYST in 1 (3%), and STXBP2 in 1 (3%) with a mean interval to diagnosis of 28.3 months. Among 19 patients who underwent HSCT, 11 neurologically improved, 4 were stable, one relapsed, and 3 died. Among 14 non-transplanted patients, only 3 improved or had stable disease, one relapsed, and 10 died. Isolated CNS-HLH is a rare and often overlooked cause of inflammatory brain disease. HLH-directed therapy followed by HSCT seems to improve survival and outcome.

Race-neutral equations for assessment of lung function in children with thalassemia.

The aim of this study was to assess pulmonary dysfunction in children with transfusion-dependent thalassemia (TDT) using the Global Lung Function Initiative (GLI) 2022 race-neutral spirometric reference equations and to determine the main predicting factors. The spirometric results of 68 children with TDT were compared to the results of 68 healthy control subjects using both GLI-2012 reference equations for Caucasians and GLI-2022 global equations. Associations between the spirometric data and various anthropometric, clinical, and laboratory parameters were analyzed to detect predictors of pulmonary dysfunction in this group of patients. Children with TDT showed significantly lower values of FVC and FEV1 with a predominance of the restrictive pattern (23.53%). Thalassemic children with the restrictive pattern were significantly older, had a longer duration of regular blood transfusion, lower height, weight, and BMI z-scores, higher average serum ferritin, and higher frequency of having a serum ferritin level >2500 ng/mL. The strongest predictor for having a restrictive spirometric pattern was high serum ferritin. Our analysis shows that the transition from GLI-2012 spirometric reference equations for Caucasians to the GLI-2022 global equations has led to a reduction in the prevalence rate of restrictive pulmonary dysfunction in children with TDT, which should not affect the patient outcome in the long term. Asymptomatic children with TDT exhibited a restrictive spirometric pattern in a significant proportion. The most important predictor was high serum ferritin. We encourage the inclusion of pulmonary function testing in the routine monitoring of patients with TDT, especially in older patients and those with iron overload.

Is hypoalbuminemia a risk factor for high-dose methotrexate toxicity in children with acute lymphoblastic leukemia?

BACKGROUND: Repeated high-dose methotrexate (HDMTX) is a critical component of contemporary childhood acute lymphoblastic leukemia (ALL) treatment regimens. Serum albumin is considered a carrier of methotrexate (MTX) in the blood. Hypoalbuminemia is not a rare finding in children with leukemia. This study aimed to investigate the relationship between pre-infusion serum albumin and possible HDMTX toxicities. METHODS: Thirty Egyptian children with ALL were consecutively enrolled in the study between May 2018 and July 2020. They were prospectively followed up while receiving HDMTX during the consolidation phase of the TOTAL study XV protocol. HDMTX was administered intravenously as a 24-h infusion every 2 weeks. Doses of 2.5 g/m2 were used for low-risk patients and 5 g/m2 for standard/high-risk patients. The Common Terminology Criteria for Adverse Events (V.4.03) was used to report the observed toxicities after HDMTX cycles. Plasma MTX levels were estimated at 24 h (MTX24) from the beginning of HDMTX infusion in the first consolidation cycle. Serum albumin level was determined before HDMTX administration, and pre-infusion hypoalbuminemia was defined when serum albumin was <3.5 g/dL. RESULTS: The patients' age ranged from 2.3 to 13.3 years at diagnosis, and most of them had B cell ALL (86.7%). Overall, 120 HDMTX cycles were analyzed, equally distributed between low and standard/high risk. Grade 3-4 anemia, grades 3-4 thrombocytopenia, febrile neutropenia, and oral mucositis were significantly more frequent in HDMTX cycles with pre-infusion hypoalbuminemia than those with normal pre-infusion albumin (p=0.003, p=0.007, p=0.006, and p=0.001, respectively). In addition, pre-infusion hypoalbuminemia was significantly associated with additional hospitalization due to HDMTX toxicity (p=0.031). Most HDMTX toxicities were comparable irrespective of the MTX dose. Oral mucositis was more frequently encountered in the 2.5 g/m2 than the 5 g/m2 HDMTX cycles (46.7 vs. 26.7%, p=0.023). A significantly longer hospitalization (due to HDMTX toxicity) was observed in the 5 g/m2 HDMTX cycles (median= 7 days vs. 4 days, p=0.012). CONCLUSIONS: Serum albumin levels should be checked before starting HDMTX cycles, especially in resource-limited settings where malnutrition is common, and serum MTX monitoring may not be available. Optimizing serum albumin levels before HDMTX may help decrease the possibility of HDMTX toxicities.

Positive Impact of Clinical Audit on Appropriateness of Laboratory Investigations for Glucose-6-Phosphate Dehydrogenase-Deficient Patients in the Emergency Department.

OBJECTIVES: The authors aim to assess the use of investigations for patients with acute hemolytic anemia due to glucose-6-phosphate dehydrogenase (G6PD) deficiency and to ensure guidelines application during practice to reduce the misuse of hospital resources in the emergency department (ED). METHODS: A cross-sectional study was conducted at a pediatric tertiary hospital on children presenting to the ED with an acute hemolytic crisis due to G6PD deficiency. Initial investigations were collected from patients' records and compared to local hematology unit guidelines. After a period of basic training and guideline dissemination to the residents, a re-audit was conducted. Percentages of the requested investigations in each audit were calculated and compared using Chi-square test. RESULTS: Fifty-three acute hemolytic anemia patients were included in the initial audit and 58 patients in the re-audit. In the initial audit, the most commonly requested nonindicated investigations were the Coombs test and liver enzymes. The requested nonindicated chemistry labs dropped from 74% in the initial audit to 14% in the re-audit (p < 0.001), and Coombs test from 81% to 12% (p < 0.001). CONCLUSIONS: A large proportion of requested investigations for children presenting with G6PD acute hemolytic crisis are nonindicated. Education of medical staff about the guidelines and their continuous assessments through audits were effective at reducing unnecessary diagnostic tests.