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BCR::ABL1-like pre-B-ALL comprises a myriad of genetic lesions making molecular diagnosis challenging and expensive. Its frequency and outcome are less studied in resource-constraint settings.154 pre-B-ALL cases (0-12 years) were enrolled as group 1 (37 cases of B-other-ALL) and group 2 (117 patients with recurrent translocations/ hyperdiploidy). Group 1 was evaluated for BCR::ABL1-like genetic lesions and copy-number abnormalities (CNAs) as per our published PACE approach supplemented with targeted RNA sequencing.BCR::ABL1-like frequency was 5.2% (8 of 154) and 22% (8 of 37) with the PACE approach alone in the whole and B-other-ALL cohort, respectively. The addition of targeted RNA-sequencing had led to the frequency increasing to 9% (14 of 154) and 38% (14 of 37) in the whole and B-other-ALL cohort, respectively. P2RY8::CRLF2, IGH::CRLF2, and RCSD1::ABL1 were noted in 8 (57.1%), 4 (28.6%), and 2 (14.3%) patients, respectively. CNAs were noted in 56.7% (21 of 37) of patients. The BCR::ABL1-like group had a significantly higher initial WBC count of ≥ 50,000/mmThe sensitivity of detecting BCR::ABL1-like lesions had increased significantly from 22% using the PACE approach alone to 38% in B-other-ALLs with the integrated approach. Although outcomes were not statistically different, a higher percentage of relapses were noted in the B-other-ALL group.

Introduction: Current study is a 4 year experience in diagnosis and screening of bone marrow failure cases using a targeted sequencing panel. Methods: A total of 171 cases underwent targeted NGS and were categorized as suspected inherited bone marrow failure syndrome (IBMFS) group (106/62%) and idiopathic aplastic anemia (IAA) group (65/38%) based on clinical and laboratory criteria. Results: 110 (64%) were pediatric (0-12 years) and 61 (36%) adolescent and adults (13-47 years). In suspected IBMFS group, 47 (44%) were positive for a pathogenic variation while in IAA group, 8 (12%) revealed a silent germline pathogenic variation. Whole exome sequencing performed in 15/61 suspected IBMFS group cases, revealed a clinically important variation in 3 (20%) cases. The targeted panel helped in establishing a diagnosis in 44% (27/61) of phenotypically heterogenous unclassified bone marrow failure syndrome cases and also led to amendment of clinical diagnosis in 5 (4.7%) of genotyped cases. Conclusion: Overall targeted NGS panel yield was comparable to western data, however, this was achievable at 1/5th the cost, making it a cost-effective panel for resource constraint settings.

Patients with non-transfusion dependent thalassemia (NTDT) develop variable degrees of iron overload. Possible genes which may be implicated in causing iron overload are hepcidin (HAMP) and hemojuvelin (HFE). There is variable data assessing the role of c.-582Y A > G HAMP gene and H63D hotspot in HFE-1 gene in causing iron overload, while role of HFE-2 gene is undetermined. Twenty-five patients with NTDT (≥ 10 years) were assessed for iron overload. Genetic analysis for β-globin, α-globin, HAMP, HFE-2 and C282Y and H63D hotspots in HFE-1 genes was performed. T2*MRI demonstrated elevated LIC in 48% patients. No mutations were detected in HAMP gene or HFE-1 hotspots. Four single nucleotide variations (SNV) were detected in HFE-2 gene in 4 (20%) patients, including a novel SNV, p.Gln315Arg in 2 patients in heterozygous state. This is a likely pathogenic mutation; however, in heterozygous state, it did not lead to iron overload. HAMP and HFE-2 gene variations were infrequently seen in this pilot study, with no significant impact on iron overload. Presence of SNV p.Gln315Argin HFE-2 gene needs to be evaluated in larger sample sizes in our population to determine the incidence in homozygous state and its association with iron overload. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12288-021-01442-9.

In current study, copy number alteration (CNA) status and CNA risk profiles of IKZF1plus, UK-ALL CNA risk groups and MRplus score, were evaluated for clinical and prognostic impact in a cohort of 493 B-ALL cases diagnosed and treated under ICICLE trial at two major oncology centres of Northern India. Overall CNA frequency was 59% with 60% of cases showing 2-loci deletion. CDKN2A/B deletion was the most common CNA (36.3%), while IKZF1 deletion and IKZF1plus profile were noted in 19.5% and 13.4% of cases respectively. IKZF1 deletions and other CNA risk profiles were all signifcantly associated with poor/high risk clinical and genetic profile parameters (p

Introduction Children with cancer are immunocompromised due to the disease per se or anticancer therapy. Children are believed to be at a lower risk of severe coronavirus disease 2019 (COVID-19) disease. Objective This study analyzed the outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children with cancer. Materials and Methods A retrospective analysis was performed on patients (≤ 14 years) with cancer attending the pediatric oncology services of our institute who tested positive for the SARS-CoV-2 infection and those who had COVID-19 disease between August 2020 and May 2021. Real-time reverse transcriptase-polymerase chain reaction performed on the nasopharyngeal swab identified the SARS-CoV-2 infection. The primary endpoints were clinical recovery, interruption of cancer treatment, and associated morbidity and mortality. Results Sixty-six (5.7%) of 1,146 tests were positive for the SARS-CoV-2 infection. Fifty-two (79%) and 14 (21%) patients had hematolymphoid and solid malignancies. Thirty-two (48.5%) patients were asymptomatic. A mild-moderate, severe, or critical disease was observed in 75% (18/24), 12.5% (3/24), and 12.5% (3/24) of the symptomatic patients. The “all-cause” mortality was 7.6% (5/66), with only one (1.5%) death attributable to COVID-19. Two (3%) patients required ventilation. Two (3%) patients had a delay in cancer diagnosis secondary to COVID-19 infection. Thirty-eight (57.6%) had a disruption in anticancer treatment. Conclusion Children with cancer do not appear to be at an increased risk of severe illness due to SARS-CoV-2 infection. Our findings substantiate continuing the delivery of nonintensive anticancer treatment unless sick. However, SARS-CoV-2 infection interrupted anticancer therapy in a considerable proportion of children.

Disorders associated with multiple vertebral segmentation defects may have additional rib anomalies in form of absence or hypoplastic ribs, fanning of ribs, etc. Spondylocostal dysostosis is genetic disorder with abnormal vertebral segmentation and rib anomalies. Diagnosis is often delayed because of non-familiarity with the characteristic features. There are six genes identified for spondylocostal dysostosis, of which SCDO5 is responsible for autosomal dominant form of the disorder. Retrospective study was conducted in Genetic and Metabolic unit of a tertiary hospital in north India over a period of 9 years. Twenty patients with a clinical diagnosis of congenital scoliosis were identified, and reviewed. Three patients were discussed in an earlier report and 11 subsequent patients, are described in this case series here. The median age at presentation was 34 months. The patients showed hemivertebrae, vertebral fusion, fusion of ribs, fanning of ribs. Hydrocephalus/ventriculomegaly was found in three cases and diastematomyelia was identified in one case. Other associated anomalies included corpus callosal agenesis, club foot and capillary malformation. One parent showed rib/spinal defects in two cases. Further studies are needed to characterise the phenotype and genetic basis of scoliosis in Indian patients.