Genital Graft-versus-Host Disease in Children: An Underdiagnosed and Undertreated Entity.

Genital graft-versus-host disease (GVHD) is an underdiagnosed and poorly recognized complication, especially in the pediatric population. We report our data on children with genital manifestations of GVHD and their unique clinical features. The study included children up to age 18 years who underwent hematopoietic stem cell transplantation (HSCT) over a 20-year period from February 2002 to February 2022. A total of 1035 children underwent HSCT during the study period. Genital GVHD was documented in 164 children (15.8%). Among these 164 children, 23 (14%) were age <2 years, 98 (59.8%) were age 2 to 10 years, and 43 (26.2%) were age ≥10 years. The conditioning regimen was myeloablative in 122 children (74.4%) and reduced intensity in 42 children (25.6%). Donor type was matched related donor in 62 (37.8%), matched unrelated donor in 44 (26.8%), and haploidentical in 34 (20.7%). Peripheral blood stem cells (PBSCs) were used in 78.7% of the children (n = 129), and sex mismatch was noted in 31.1% of genital GVHD cases (51 of 164). The overall incidence of chronic oral GVHD was 33% (342 of 1035), and of these, 47.9% (164 of 342) also had genital GVHD. Patients with genital GVHD ultimately may require surgical management; 21.5% (22 of 103) of boys with genital GVHD ultimately required circumcision for phimosis, and 1 female patient developed hematocolpos necessitating surgical management. Our case series highlights the significant association between chronic oral GVHD and genital GVHD. Given the strong association between oral GVHD and genital GVHD in children, it is imperative to examine the genital area in all children on follow-up for chronic GVHD. Donor-recipient sex mismatch and use of PBSC grafts predispose to chronic genital GVHD. Early identification and treatment of genital GVHD may help prevent complications, including scarring and phimosis.

Treosulfan-Based Conditioning in Matched Family, Unrelated and Haploidentical Hematopoietic Stem Cell Transplantation for Genetic Hemophagocytic Lymphohistiocytosis: Experience and Outcomes over 10 Years from India.

We aimed to analyze data in children with primary hemophagocytic lymphohistiocytosis (HLH) who underwent hematopoietic stem cell transplantation (HSCT). We performed a retrospective study where children up to 18 years, with primary HLH and who underwent HSCT from January 2011 to December 2019, were included. Twenty-five children with genetic HLH underwent HSCT, including variants (Griscelli syndrome (GS2) 7, Chediak-Higashi syndrome (CHS) 2, XIAP mutation 2). Donors were matched family 8 (32%), umbilical cord blood unit 3 (12%), matched unrelated 2 (8%), haploidentical HSCT 12 (48%), (TCR alpha/beta depletion 2 and post-transplant cyclophosphamide 10). With treosulfan-based conditioning, engraftment was achieved in 23/25 (92%) transplants (100% in haplo-HSCT), with sustained complete chimerism in 87%. Disease-free survival was noted in 2/3 children with stable mixed chimerism. Graft-versus-host disease (GVHD) of grade I/II was noted in 6 (24%), grade III in 3 (13%); chronic limited skin GVHD in 2 (12%) children. Overall survival was 72% (87.5% in matched donor, 66.7% in the haplo-HSCT), 71% in GS2, 50% in CHS, 100% in XIAP. HSCT is curative in primary HLH with acceptable disease-free survival with mixed chimerism. Haplo-HSCT is a viable option for those without matched family or unrelated donors.

Study of transfusion-related iron overload (trio) in pediatric patients with hematological malignancy and bone marrow failure syndromes.

BACKGROUND: Pediatric patients with hematological malignancy and bone marrow failure syndrome receive multiple transfusions before diagnosis and treatment. Iron overload leads to damage to vital organs like the heart, liver, thyroid, Gonads, Pancreas. MATERIALS AND METHODS: A prospective study was done from June 2017-December 2019 in a tertiary care pediatric hematology oncology unit in northern India on children diagnosed with hematological malignancy and bone marrow failure syndromes receiving packed cell transfusion. After due ethical considerations and patient consent, the details were documented in predesigned proforma. All cases were planned to be investigated with Liver function test, Thyroid function test, Serum ferritin level, 2 D Echocardiography, Ultrasonography of abdomen, and MRI of the abdomen at admission and six months of enrollment. RESULTS: Out of 58 cases enrolled, ferritin levels were high in 65% of subjects at the start of treatment and 76% at the endpoint. Mean ferritin level was 725 ng/ml at baseline and 1268 ng/ml end of 6 month follow up period. Fifty-seven percent had a ferritin level above 1000 ng/ml, which correlated to basal ferritin level (P-value 0.005). The final ferritin level correlated strongly with the final number of packed cell transfusions (P-value 0.0002). Functional derangement of the liver was evident biochemically in 13.7% before starting treatment and 31.8% at six months follow-up period. Echocardiography detected diastolic dysfunction in 2% of patients at baseline before starting treatment and increased to 22% in 6 months follow-up period. The percentage of subclinical hypothyroidism increased from 22.8% to 48.8% during treatment. CONCLUSION: Like transfusion-dependent anemias, children with hematological malignancy and bone marrow failure syndrome on chronic transfusion are at risk of transfusion-related iron overload and organ damage.

Survey of Mental Health of Dentists in the COVID-19 Pandemic in the UK.

AIM: To assess the impact of work-related changes on the mental health (MH) of dentists during the peak of COVID-19 pandemic in the UK. MATERIALS AND METHODS: Dentists involved in certain treatments, for example, high-speed drilling procedures, generate infectious aerosols. These Aerosol Generating Procedures (AGPs) are at the highest risk of transmission of coronavirus. During the COVID-19 pandemic, a significant number of dentists in the UK were restricted from providing treatments to reduce the risk of viral transmission. Some of the dentists providing urgent dental treatment were involved in AGPs. Significant and sudden changes in the delivery of dental care in the current pandemic may have impacted the MH of dentists. An online survey was conducted, using validated tools to measure the MH symptoms and stress. Pearson's chi-squared test of independence was used for statistical analysis. RESULTS: Overall, 123 dentists participated in the survey. The prevalence of anxiety-related symptoms was 71% (95% CI 0.62-0.78), depression-related symptoms was 60% (95% CI 0.51-0.68), and stress was 92% (95% CI 0.86-0.96). Dentists working in the independent sector had more psychological symptoms compared with those in the public sector (P = 0.014). CONCLUSIONS: Working in the public sector appeared to have a protective effect. Almost all the dentists in this survey were experiencing MH symptoms and stress. Further research is needed to assess the long-term effect of the COVID-19 pandemic on dentists.

Augmented immunosuppression and PTCY-based haploidentical hematopoietic stem cell transplantation for thalassemia major.

Alternate donor HSCT for thalassemia major from a matched unrelated donor or haploidentical family donor is a feasible therapeutic option in children with no matched family donor. Aggressive pretransplant immunosuppression, reduced toxicity conditioning, and PTCY result in excellent thalassemia-free survival. We describe here our experience in this cohort. We performed a retrospective analysis of the data on children who underwent a haploidentical HSCT for thalassemia major with PTCY at our center from August 2017 to August 2019. All children received pretransplant immune suppression for 6 weeks with fludarabine and dexamethasone, hypertransfusion and chelation with intravenous desferrioxamine. Conditioning included thiotepa, fludarabine, rabbit ATG, and cyclophosphamide, and GvHD prophylaxis included PTCY with tacrolimus. Twenty children were included and nineteen children engrafted. Acute hypertension occurred in five children, bacterial infection in eight children and viral respiratory infection in three children. Three children suffered from graft rejection. Reactivation of viruses namely CMV, adenovirus, and BK virus was seen in 60% of children. Grades 1-2 acute GvHD of the skin in four children (20%) and limited chronic GvHD of the skin in four children (20%). Immune cytopenia was documented in three children (15%). Haploidentical HSCT offers a therapeutic option for children with thalassemia major with no suitably matched family or unrelated donors. Our reduced toxicity regimen with PTCY offers a DFS of 75% and OS of 95% with low transplant-related mortality of 5%.

Seasonal Variation and Dengue Burden in Paediatric Patients in New Delhi.

OBJECTIVE: We conducted a study to find a relationship between main weather parameters with admission of positive dengue cases in a tertiary hospital. METHODS: Retrospective analysis was undertaken to identify epidemiological trend of dengue in 2016 from paediatric wards of a tertiary hospital in New Delhi. Data were collected on patient particulars and daily weather from January to December 2016. RESULTS: A total of 266 confirmed cases of dengue were considered. Relative humidity (RH) was associated with burden of positive dengue cases. On week-wise analysis, each surge of dengue admission was preceded by heavy rain 4-6 weeks earlier. Monthly averaged daily temperature range and RH were noted to have strong correlations with dengue burden, keeping an interval of 2 months in between. CONCLUSIONS: Weather parameters seem to influence magnitude of dengue epidemic, particularly in dengue season. There is need to have an in-depth study about developing a prediction model for dengue epidemic.