Pediatric immune thrombocytopenia (ITP) is a heterogeneous autoimmune disorder with variable clinical outcomes. While most children experience spontaneous remission, 10 to 20% progress to chronic ITP. Early prediction to chronicity remains a clinical challenge. This study aimed to develop and validate a logistic regression-based model integrating immune features to predict chronicity in ITP among children. In this prospective cohort study, we stratified 108 pediatric ITP patients into newly diagnosed with remission (n = 48), progressors (n = 13), and chronic ITP (n = 47). We analyzed peripheral blood using multicolor flow cytometry for 79 immune subsets. We recorded clinical variables including bleeding symptoms, platelet count, and recent infections/vaccinations. We performed multivariable logistic regression using immune parameters alone and in combination with clinical features. Model performance was assessed via 5-fold cross-validation and validated on the progressor cohort. Patients with Chronic ITP Exhibited a Distinct Immunological Feature Characterized by Reduced CD4/CD8 Ratio, na & iuml;ve Th and na & iuml;ve Tc Cell and Increased Effector Memory, Tc Cell Percent, Senescent T Cell (CD57+, PD1+), B Memory and Class Switched Memory B Cells. The Immune-Only Model Identified Reduced na & iuml;ve Cytotoxic T Cells [CD8(+)CD27(+)CD45RA(+)] and Increased Double-Negative B Cells [CD19(+)CD27(-)IgD(-)] as Key Predictors (Accuracy 71.6%, Area under the Receiver Operating Characteristic Curve (AUC) 0.761, p < 0.001), Correctly Classifying 8/13 (61.5%) Progressors. In the Combined Model, Increased Frequencies of Class-Switched Memory (CSW) B Cells [CD19 + CD27 + IgM-IgD-], Terminally Differentiated Effector Cytotoxic [CD8(+)CD28(-)] T Cells, more Specific Double Negative (DN) B Cells Population of CD21-/lowCD38-Cells[CD19 + CD21-/Low CD38-CD27-IgD-] and Clinically, Epistaxis and Absence of Abrupt Onset of Bleeding Were Associated with Chronicity, Improving Overall Accuracy 82.8%, (AUC 0.905, p < 0.001) and Correctly Classifying 10/13 (76.92%) Progressors. Integration of clinical features with detailed immune profiling enables early and accurate prediction of chronic ITP in children. These findings support its potential in selecting appropriate management strategies warranting validation in larger multicentric cohorts.

Background:Almost 90% of childhood cancers occur in lower income- and middle-income countries (LMICs) like India, leading to a growing population of cancer survivors. However, data on long-term outcomes and late effects are limited. The Indian Childhood Cancer Survivorship (C2S) Study was envisaged to build a nationwide survivor cohort and systematically capture treatment exposures and long-term outcomes. Methods:The C2S study is a prospective multicentric observational cohort initiated in 2016 under the Indian Pediatric Hematology Oncology Group (InPOG-LE-16-01). Children diagnosed with cancer before 18 years of age and in remission post-treatment were enrolled. Demographic, clinical, and treatment exposure data were collected at respective centres and monitored centrally. Follow-up was conducted every three months, assessing survival, relapse, and abandonment rates. Findings:As of December 2024, the study includes data from 20 centres across India with 5419 survivors being enrolled, with survival data available for 5140. Acute leukemia was the most common diagnosis (40.9%). Common therapeutic exposures included chemotherapy (94.7%), surgery (30.3%), and radiotherapy (26.3%). The 5-year overall survival (OS) and event-free survival (EFS) rates for the entire cohort were 94.5% (95% CI: 93.7-95.3)% and 89.9% (95% CI: 88.8-91.0)%, respectively. For the 2266 survivors with ≥2 years post-treatment follow-up, 5 y-OS and EFS were 98.2 (95% CI: 97.5-98.7)% and 95.7 (95% CI: 94.7-96.6)%, respectively. Interpretation:The C2S study represents the first structured attempt to build a nationwide childhood cancer survivors' cohort in India. This cohort will serve as a denominator for future research on late effects, support the development of survivorship guidelines, and inform policy planning in India and comparable LMIC settings. Funding:There was no dedicated funding for this study.

Venous thromboembolism in children has risen sharply, likely due to improved survival of critically ill patients, increased central line use etc. While LMWH has long been the standard of care, FDA approval of DOACs has introduced an effective and convenient alternative Hence, we conducted a retrospective review of pediatric VTE cases to evaluate usage patterns, limitations, and adverse effects. Retrospective observational study included children (< 18 years) with venous thromboembolism treated with rivaroxaban or dabigatran between January 2023 and October 2024. Patients were selected and dosed according to EINSTEIN-Junior and DIVERSITY trial criteria. Clinical, laboratory, and imaging data were reviewed and outcomes including thrombus resolution, treatment modifications, and adverse events were assessed at predefined follow-up intervals. Among 53 children with VTE, 26 (14 rivaroxaban, 12 dabigatran) were analysed. Most patients (69

India bears a high burden of thalassemia, underscoring the need for enhanced awareness, systematic screening, and standardized, high-quality care. In the absence of indigenous guidelines, gaps remain in knowledge and care delivery. To address this, the Pediatric Hematology Oncology Chapter of the Indian Academy of Pediatrics (IAP-PHO) is issuing evidence-based regional guidelines tailored to the Indian context. The primary objective of these guidelines is to establish nationally accepted standards for the diagnosis, comprehensive management, and prevention of thalassemia syndromes, incorporating the latest and locally relevant evidence. These evidence-based guidelines were developed through structured deliberations by 67 national experts under the IAP-PHO, incorporating iterative literature review, expert consensus, and context-specific considerations for India. The evidence quality (levels A-D, X) and strength of recommendation (strong, moderate, weak) are graded using the updated American Academy of Pediatrics framework. These guidelines provide a comprehensive, evidence-based framework for thalassemia care in India, encompassing prevention, diagnosis, transfusion and chelation, complication management, curative therapies and systems-based care, including day-care services and transition to adult care. Regular transfusion therapy with leukodepleted packed red cells to maintain pre-transfusion hemoglobin of 9.5–10.5 g/dL is the cornerstone of management in transfusion-dependent thalassemia (TDT), with individualized adjustment in special situations such as cardiac dysfunction. Iron chelation therapy should be initiated after 10–20 transfusions or when serum ferritin (SF) exceeds 1000 ng/mL; oral deferasirox is the preferred first-line agent. Combination therapy using deferasirox, and/or deferiprone and/or desferrioxamine is recommended when monotherapy with either deferasirox or deferiprone fails to reduce SF to < 2500 ng/mL or in the case of poor tolerance to one agent or when there is evidence of significant organ iron overload on T2*MRI (magnetic resonance imaging); de-escalation of chelation is recommended when SF approaches < 500 ng/mL. Comprehensive multidisciplinary care, incorporating systematic screening and timely interventions for cardiac, hepatic, endocrine, and skeletal complications, is strongly recommended. Early counseling for hematopoietic stem cell transplantation (HSCT) should be offered at diagnosis, with transplantation preferably performed at a younger age. Universal antenatal screening, cascade screening, and access to prenatal diagnosis, are critical to reducing disease burden. Emerging disease-modifying therapies may be considered in selected patients, with evolving pediatric data. Delivery of care through dedicated thalassemia day-care centers and structured transition to adult services is recommended to ensure continuity of care and best quality of life.

Abstract Introduction Congenital hepatoblastoma (CHB) is a rare subset of hepatoblastoma presenting in the neonatal period or early infancy, accounting for less than 10% of cases. Historically considered aggressive, outcomes have improved with multimodal therapy. Case-presentations We report four infants presenting within the first 2 months of life with abdominal mass, predominantly in the right upper quadrant, and markedly elevated alpha-fetoprotein levels. Antenatal imaging was normal in all cases. Imaging revealed hepatic masses ranging from 8.4 to 10.4 cm. All patients underwent early surgical resection with histopathological confirmation of CHB, followed by cisplatin-based chemotherapy. Three had pure fetal histology, and one had mixed epithelial and mesenchymal features. All patients remain alive and disease-free at follow-up ranging from 4.3 to 12.7 years. Conclusion CHB, though rare, has favorable outcomes with timely surgical resection and chemotherapy. A multidisciplinary approach is essential to optimize survival in these challenging neonatal cases. Learning points

Megaloblastic anemia, characterized by macrocytic anemia, is most commonly caused by nutritional vitamin B12 deficiency; however, inherited disorders of cobalamin absorption should be considered in children with adequate dietary intake. One such disorder is Imerslund-Gräsbeck syndrome (IGS), a rare autosomal recessive condition characterized by selective intestinal malabsorption of vitamin B12 due to mutations in the CUBN or AMN genes. We report a 7-year-old boy, born of a third-degree consanguineous marriage, who presented with generalized rash, easy fatigability, and recurrent oral ulceration. Examination revealed pallor and hyperpigmented knuckles without organomegaly. Growth parameters were between the 10th and 25th centiles. Investigations showed severe macrocytic anemia (hemoglobin 2.5 g/dL), leukopenia, thrombocytopenia, markedly reduced vitamin B12 levels (<50 pg./mL), and peripheral smear findings of macrocytosis with hypersegmented neutrophils. In view of adequate nutritional intake, further evaluation for malabsorption was undertaken. There was no clinical evidence of gastrointestinal malabsorption, and anti-intrinsic factor antibody testing was negative. Urinalysis demonstrated mild proteinuria. Genetic analysis identified a homozygous mutation in the AMN gene, confirming the diagnosis of IGS. The child started on parenteral vitamin B12 therapy with plans for lifelong supplementation at intervals guided by clinical response. IGS should be suspected in children with megaloblastic anemia despite adequate dietary intake, particularly in the presence of proteinuria, parental consanguinity, or a poor response to oral supplementation. Early diagnosis and timely initiation of lifelong vitamin B12 therapy are essential to ensure optimal hematological recovery, growth, and neurodevelopmental outcomes.

Vitamin B12 deficiency is a common yet frequently underrecognized nutritional disorder with important public health implications, particularly in low- and middle-income countries where maternal deficiency, vegetarian dietary practices, and food insecurity are prevalent. In children, deficiency may lead to irreversible neurodevelopmental impairment, growth failure, and hematological abnormalities, making early recognition essential. The clinical spectrum ranges from asymptomatic biochemical deficiency and isolated macrocytic anemia to developmental regression, seizures, movement disorders, peripheral neuropathy, and pancytopenia, with neurological manifestations often preceding hematological changes. Diagnosis requires integration of clinical features with laboratory evaluation, including complete blood count, peripheral smear, serum vitamin B12 estimation, and functional biomarkers such as methylmalonic acid and homocysteine, which improve diagnostic accuracy in borderline or atypical cases. Molecular testing has expanded the identification of inherited disorders affecting vitamin B12 absorption and metabolism, enabling timely lifelong management. Prompt replacement therapy is the cornerstone of treatment and should not be delayed when clinical suspicion is high. Oral supplementation is effective for most dietary deficiencies, whereas parenteral therapy is indicated for severe anemia, neurological involvement, malabsorption, or inherited cobalamin disorders. Early treatment results in rapid hematological recovery, but delayed intervention may leave permanent neurological sequelae despite biochemical correction. Beyond individual patient care, strengthening maternal nutrition, targeted screening of high-risk populations, food fortification, and public awareness are critical strategies to reduce the burden of vitamin B12 deficiency and prevent avoidable disability. This review summarizes current evidence on the diagnosis and treatment of pediatric vitamin B12 deficiency and highlights practical approaches for improving clinical outcomes.

Diamond–Blackfan anaemia (DBA) is a rare inherited disorder marked by early-onset macrocytic anaemia and erythroid hypoplasia, resulting from mutations in ribosomal protein genes. Despite growing genetic insights, data on functional validation remain limited in India; here we report a novel RPS10 mutation with functional validation and provide genotype–phenotype correlation by integrating our findings with all previously reported RPS10 variants. A clinically suspected Diamond–Blackfan anaemia (DBA) case was evaluated through haematological profiling, bone marrow examination, and erythrocyte adenosine deaminase (eADA) activity measurement. Whole exome sequencing (WES) was followed by Sanger sequencing to identify and validate a novel pathogenic variant. Gene expression of ribosomal and regulatory genes was analysed by quantitative RT-PCR, and rRNA processing analysis was carried out to assess functional impact. The proband presented with severe macrocytic anaemia, reticulocytopenia, and erythroid hypoplasia consistent with Diamond–Blackfan anaemia (DBA). Whole exome sequencing identified a novel heterozygous nonsense variant in RPS10 (c.206G > A; p.Trp69Ter), and Sanger sequencing confirmed the variant as de novo. Gene expression analysis revealed significant upregulation of TP53 and downregulation of RPS10 and GATA1, indicating ribosomal dysfunction and activation of the p53 pathway. Additionally, the rRNA processing defect validated the pathogenicity of the novel RPS10 variant. This study identifies a novel de novo nonsense variant in RPS10 associated with Diamond–Blackfan anaemia, with supporting functional evidence of haploinsufficiency and p53 pathway activation. These findings expand the mutational spectrum of RPS10 and underscore the diagnostic value of integrating genomic and functional analyses in rare haematological disorders, while also contributing to ongoing efforts to delineate genotype–phenotype correlations in DBA.