Leukocyte adhesion deficiency (LAD) syndrome is a group of inborn errors of immunity characterized by a defect in the cascade of the activation and adhesion leading to the failure of leukocyte to migrate to the site of tissue injury. Three different types of LAD have been described. The most common subtype is LAD type 1 (LAD1) caused due to defects in the ITGβ2 gene. LAD type 2 (LAD2) is caused by mutations in the SLC35C1 gene leading to a generalized loss of expression of fucosylated glycans on the cell surface and LAD type 3 (LAD3) is caused by mutations in the FERMT3 gene resulting in platelet function defects along with immunodeficiency. There is a paucity of data available from India on LAD syndromes. The present study is a retrospective analysis of patients with LAD collated from 28 different centers across India. For LAD1, the diagnosis was based on clinical features and flow cytometric expression of CD18 on peripheral blood leukocytes and molecular confirmation by Sanger sequencing. For patients with LAD3 diagnosis was largely based on clinical manifestations and identification of the pathogenic mutation in the FERMT3 gene by next-generation Sequencing. Of the total 132 cases diagnosed with LAD, 127 were LAD1 and 5 were LAD3. The majority of our patients (83%) had CD18 expression less than 2% on neutrophils (LAD1°) and presented within the first three months of life with omphalitis, skin and soft tissue infections, delayed umbilical cord detachment, otitis media, and sepsis. The patients with CD18 expression of more than 30% (LAD1+) presented later in life with skin ulcers being the commonest manifestation. Bleeding manifestations were common in patients with LAD3. Persistent neutrophilic leukocytosis was the characteristic finding in all patients. 35 novel mutations were detected in the ITGβ2 gene, and 4 novel mutations were detected in the FERMT3 gene. The study thus presents one of the largest cohorts of patients from India with LAD, focusing on clinical features, immunological characteristics, and molecular spectrum.

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Introduction The recent advances in cancer treatment have resulted in significant improvement in the outcome of pediatric cancers. However, febrile neutropenia (FN) is the most important cause of mortality and morbidity in pediatric cancer patients and is a crucial limiting factor for the outcome. The greatest threat that we are facing is the emergence of pan drug-resistant (PDR) organisms. Objectives To study bacterial organisms causing bloodstream infections (BSI) during febrile neutropenia episodes, their antibiotic sensitivity pattern, impact on treatment outcome during the intensive phase of chemotherapy, and the association between prior administration of antibiotics and emergence of multidrug-resistant organisms (MDR). Materials and Methods This retrospective study was conducted in patients between the age group of 0 to 18 years who were treated for malignancies in the division of pediatric oncology at a tertiary center from August 2017 to December 2020. Blood cultures were collected under aseptic precautions, and they were processed as per the Clinical and Laboratory Standard Institute Guideline (CLSI) 2017. Results A total of 122/159 (76.7%) patients were diagnosed to have hematological malignancies, and 37/159 (23.3%) patients were found to be suffering from solid tumors. A total of 309 episodes of FN were documented and 386 cultures were sent, out of which 87/386 (22.53%) cultures were positive for bacteria and 2/386 (2.2%) for fungi. Gram-negative isolates were seen in 51/87 (58.62%) cultures and Gram-positive in 36/87 (41.37%) cultures. Burkholderia cepacia and coagulase-negative Staphylococci (CONS) were the commonest found Gram-negative and Gram-positive bacteria, respectively. MDR bacterial strains were seen in 44/87 (50.57%) cultures and PDR strains in 8/87 (9.2%) cultures. Resistance was higher with Klebsiella species and CONS. There were six mortalities during the induction phase of acute leukemia treatment, out of which 4/6 (66.66%) were due to MDR infections, 1/6 (16.6%) due to fungal infection and chemotherapy refractoriness each. Conclusion Proven bacterial infections were determined in 22.53% of febrile neutropenia episodes. Most BSI in patients with febrile neutropenia were caused by Gram-negative bacteria. Indiscriminate use of higher antibiotics before referral led to the emergence of MDR organisms, thus compromising the outcome. Our study emphasizes the fact that antibiotic stewardship is a crucial task to counter MDR bacteremia-related morbidity and mortality in neutropenic children.

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BACKGROUND: Acute lymphoblastic leukemia(ALL) has survival rates of greater than 90% in developed nations. However various sociodemographic factors adversely affect outcome rates in low and middle income countries(LMIC). OBJECTIVE: To study induction outcome of ALL and various factors affecting it. METHODS: This was a prospective cohort study which enrolled 73 children up to age of 18 years with newly diagnosed ALL registered in our newly-established pediatric oncology division over duration of 2.5 years. Sociodemographic and clinical data was collected. Outcome was assessed using morphological remission, minimal residual disease(MRD) and mortality rate. RESULTS: Of the142 children with malignancies registered, 73 were ALL.Mean age was 7.09±4.07 years, male to female ratio 1.15:1. 15(44.12%) had severe acute malnutrition (SAM) and 14(41.17%) had moderate acute malnutrition (MAM). 27(69.23%) children were undernourished. 62(84.93%) were B-ALL, 11(15.07%) T-ALL. 28.77% had WBC counts greater than 50X109/L. t(12;21) was the most common cytogenetic abnormality. 65.76% of the patients belonged to lower socioeconomic status. There were 10 dropouts. 59(93.65%) patients completed induction of which 100% attained morphological remission and 54(91.53%) were MRD negative. There were 4 mortalities, 2(50%) due to sepsis and 2(50%) due to hemophagocytic lymphohistiocytosis(HLH). 41(65.08%) children had morbidities during induction, febrile neutropenia being the commonest. CONCLUSIONS: Successful induction outcome rates at par with high income countries(HIC) can be achieved even in resource-limited settings of LMIC with support from government schemes and NGOs. Decentralized cancer care centres can effectively pave the way in reducing cancer mortality in children of lower socioeconomic status residing in rural areas.