A Comparative Analysis of Low Dose Grafalon® Versus Thymoglobuline® as Serotherapy in Hematopoietic Stem Cell Transplant in Pediatric and Young Adult Population.

Anti-thymocyte globulin (ATG) forms an essential component of conditioning in hematopoietic stem cell transplantation (HSCT). Due to the shift of donor preference to alternate donors, reliance on rabbit-ATG (rATG) has increased. Two different forms of rATG (Thymoglobuline® and Grafalon®) are available for clinical use but data to support the use of one over the other is sparse. We retrospectively analyzed data of 144 patients who underwent allogenic-HSCT for benign hematological conditions at our center, from August 2019 to August 2023. Of these, 87 received Grafalon® and 57 received Thymoglobuline®. The majority (77.7%) underwent HSCT for hemoglobinopathies and all received pre-transplant immunosuppression. Engraftment kinetics was similar in 2 cohorts. Six patients had primary graft failure (PGF). There was no difference in the incidence of PGF stratified by serotherapy. Overall survival(OS) for the cohort was 74.9%. Kaplan-Meier estimate of OSand EFSwas significantly better in Grafalon® group than Thymoglobuline® (84.4 ± 0.04% vs 64.1% ±0.065%) (p-value= 0.04%) and (84.4 ± 0.04% and 61.2%±0.065% (p-value = 0.01)). Extensive chronic GVHD was (14%) higher in Thymoglobuline® group and (2.3%) in Grafalon®. Immune reconstitution at day + 100 was not statistically different between the two groups. On univariate analysis, Thymoglobuline® serotherapy (OR (95% CI) =4.665 (1.2-18.04))was associated with increased risk of acute grade III-IV GvHD. In our study, Grafalon® tended to have better OS, decreased incidence of acute grade III-IV GvHD, and extensive cGVHD. There was no difference in engraftment kinetics, PGF, and immune reconstitution between 2 cohorts of serotherapy.

Sirolimus-induced Hypertriglyceridemia Leads to Acute Pancreatitis and Diabetic Ketoacidosis Post Stem Cell Transplant for Sickle Cell Disease.

Sirolimus (mammalian target of rapamycin inhibitor) is a potent immunosuppressive agent, used in patients receiving hematopoietic stem cell transplant (HSCT) for Graft vs Host disease prophylaxis. Compared to calcineurin inhibitors, sirolimus has no neurotoxicity or nephrotoxicity, but sirolimus causes dose-dependent thrombocytopenia, leukopenia, delayed wound healing, hyperlipidemia, and hypertriglyceridemia. Here we report a case of acute pancreatitis and diabetic ketoacidosis in a patient with sickle cell disease post haploidentical family donor HSCT which was managed conservatively without plasmapheresis. Based on our review of the literature, this is the first reported case of developing acute pancreatitis as an adverse effect of sirolimus-induced hypertriglyceridemia leading to diabetic ketoacidosis in a recipient of HSCT.

Prevalence and Outcomes of Carbapenem-resistant Bloodstream Infection in Children With Cancer.

INTRODUCTION: Carbapenem-resistant (CR) infections cause major morbidity and mortality. Data on CR infections in children with cancer are scarce, especially from the developing world. The aim of this study was to evaluate the characteristics and outcomes of bacteremia with CR organisms (CRO) compared with bacteremia with Carbapenem-sensitive organisms in children with cancer. METHODS: This retrospective observational study was conducted in a tertiary pediatric oncology center in South India. Data on all bloodstream infections with Gram-negative organisms (CRO and Carbapenem sensitive-organisms) in children with malignancy ≤14 years of age from August 2017 to July 2021 were retrieved. The outcome was determined as survival and all-cause death 28 days after the date of Bloodstream infection (BSI) onset. RESULTS: Sixty-four Gram-negative BSI were identified, with 24% (n=15) in the Carbapenem-Resistant Bloodstream Infection (CR-BSI) group and 76% (n=49) in the Carbapenem-sensitive-Bloodstream Infection group. The patients included 35 males (64%) and 20 females (36%), with ages ranging from 1 year to 14 years (median age: 6.2 y). The most common underlying disease was hematologic malignancy (92.2%, n=59). Children with CR-BSI had a higher incidence of prolonged neutropenia, septic shock, pneumoniae, enterocolitis, altered consciousness, and acute renal failure and were associated with 28-day mortality in univariate analysis. The most common carbapenem-resistant Gram-negative bacilli isolates were Klebsiella species (47%) and Escherichia coli (33%). All carbapenem-resistant isolates were sensitive to colistin, and 33% were sensitive to Tigecycline. The case-fatality rate was 14% (9/64) in our cohort. The overall 28 days mortality was significantly higher in patients with CR-BSI than in those with Carbapenem-sensitive Bloodstream Infection (28-day mortality: 43.8% vs. 4.2%, P =0.001). CONCLUSIONS: Bacteremia with CRO has higher mortality in children with cancer. Prolonged neutropenia, pneumoniae, septic shock, enterocolitis, acute renal failure, and altered consciousness were predictors of 28-day mortality in carbapenem-resistant septicemia.

Differentiated thyroid carcinoma in children: A retrospective analysis of 125 pediatric cases from a single institution in India.

BACKGROUND: Thyroid carcinoma (TC) is extremely rare in children. We assessed the clinicopathological features, outcomes, recurrence pattern, and associated risk factors of differentiated thyroid carcinoma (DTC). METHODS: Children aged ≤14 years, pathologically diagnosed as DTC at a tertiary cancer institute between January 1998 and December 2015 were retrospectively analyzed. Survival outcomes were estimated using the Kaplan-Meier method. RESULTS: During 18 years, 125 children with DTC were treated with a male:female ratio of 1:2.3. The median age was 12 years (2-14 years). Anterior neck swelling was the commonest presentation (72.8%). Histopathology revealed papillary thyroid carcinoma (PTC) in 123 children (98.4%). Extrathyroidal extension was seen in 32 children (25.6%). Sixty-eight children (54.4%) had nodal metastases and seven had distant metastasis. Relapse developed in 12 children. All were salvaged with subsequent surgery and radioiodine therapy. Eight children had persistent disease and one had a second malignant neoplasm. The median follow-up period was 9 years 1 month (1-20 years). Five-year recurrence-free survival (RFS) was 94.8% and 5-year overall survival was 100%. Larger tumors (p-value = .001), extrathyroidal extension (p-value = .001), and nodal metastasis (p-value = .022) were significant predictors for RFS in univariate analysis. CONCLUSIONS: Pediatric DTC showed aggressive behavior characterized by a high rate of extrathyroidal extension and nodal and pulmonary metastasis. Persistent disease should be distinguished from recurrent disease as DTCs with metastatic disease remain stable for long time and usually respond well to radioiodine therapy. Our study reaffirmed favorable prognosis despite aggressive presentation and even after relapse.

Prevalence and Risk Factors for Metabolic Syndrome Among Childhood Acute Lymphoblastic Leukemia Survivors: Experience From South India.

BACKGROUND AND OBJECTIVES: Improved survival of childhood acute lymphoblastic leukemia (ALL) has diverted attention to the long-term consequences of the treatment; metabolic abnormalities being one of the most important issues. METHODS: Children diagnosed with ALL at age 14 years and younger at Regional Cancer Centre in South India who completed treatment and who were on follow-up for >2 years were enrolled in the study between April 1, 2018 and March 31, 2019. They were prospectively evaluated for the presence of metabolic syndrome (MS) and associated risk factors. RESULTS AND DISCUSSION: A total of 277 survivors of pediatric ALL were recruited during the study period. MS was present in 8.3% (n=23) and 6% (n=13) survivors by National Cholesterol Education Programme Adult Treatment Panel III (NCEPATP III) and International Diabetes Federation (IDF) criteria, respectively. The prevalence of overweight and obesity in the survivors was 9% and 13%. The prevalence of increased waist circumference, low high-density lipoprotein cholesterol, elevated triglycerides, elevated fasting glucose, and increased blood pressure were 10.5%, 28.9%, 24.9%, 2.5%, and 9%, respectively. Overweight/obese survivors were at an increased risk for developing MS (odds ratio=17.66; 95% confidence interval=6.2-50.16, P=0.001). Survivors who received cranial radiotherapy were at an elevated risk for having low high-density lipoprotein cholesterol (P=0.001). CONCLUSIONS: In our study, the prevalence of MS was higher in childhood ALL survivors, as compared with the general population. The study points to the need for regular screening of pediatric ALL survivors for early detection of MS, along with lifestyle modification in those with metabolic abnormalities, to curb the growing incidence of coronary artery disease.

Effect of Different Doses of Inhaled Corticosteroids on the Isolation of Nasopharyngeal Flora in Children with Asthma.

OBJECTIVE: To find the effects of inhaled corticosteroids and the impact of different doses of inhaled corticosteroids on the isolation of nasopharyngeal flora in asthmatic children aged 1-15 years. METHODS: The study included 75 children with asthma and 25 age-matched controls. Nasopharyngeal swabs were obtained. Bacteria were identified by standard techniques. RESULTS: Pathogenic organisms were isolated from 36% of asthmatic children and 20% of controls, the difference was not significant statistically (OR=2.25, 95% CI=0.75-6.67, P=0.13). There was no statistically significant association of using a high dose of inhaled corticosteroids with the isolation of pathogenic organisms. Usage of biomass fuel for cooking in the household of asthmatic children increases the risk of colonization (OR=3.4, 95% CI= 1.26-9.10, P=0.03). CONCLUSIONS: Inhaled corticosteroids are safe in the treatment of asthma and there is no association between different doses of Inhaled corticosteroids and isolation of the pathogenic organism.