ABSTRACT:Chronic myeloid leukemia is a myeloproliferative neoplasm which can present in chronic phase, accelerated phase, or blast crisis. Most of the children present in chronic phase. Tyrosine kinase inhibitors are used as a targeted therapy. Few children progress to blast crisis on therapy. The blast crisis occurs in the marrow. Very few cases are reported in adults with isolated central nervous system (CNS) blast crisis. Here we are reporting a rare case of isolated CNS relapse in a child.

Ghosal hematodiaphyseal dysplasia (GHDD) is an autosomal recessive disorder characterized by diaphyseal dysplasia of long bones, bone marrow fibrosis, and steroid-responsive anemia. Patients with this disease have a mutation in the thromboxane-AS1 (TBXAS1) gene located on chromosome 7q33.34. They present with short stature, varying grades of myelofibrosis, and, hence cytopenias. Patients with the above presentation were evaluated through clinical presentation, X-ray of long bones, bone marrow examinations, and confirmed by genetic testing. In this article, we present two cases: The first case is a 3-year-old boy who presented with progressive pallor and ecchymotic patches for a year. On investigation, he had bicytopenia and bone marrow fibrosis. His anemia was steroid responsive and was finally diagnosed as GHDD. The second case is a 20-month-old girl who presented with blood in stools, developmental delay, anemia, and increased intensity of long bones on X-ray. Since other investigations were normal, suspicion of GHDD was raised, and a genetic workup was conducted which suggested mutation in TBXAS1 gene, confirming the diagnosis of GHDD. Children with refractory anemia and cortical thickening on skeletogram should always be evaluated for dysplasias. Timely treatment with steroids reduces transfusion requirements and halts bone damage, thus leading to better growth and improved quality of life.

Novel silicate nanoplatelets that induce osteogenic differentiation of human mesenchymal stem cells (hMSCs) in the absence of any osteoinductive factor are reported. The presence of the silicate triggers a set of events that follows the temporal pattern of osteogenic differentiation. These findings underscore the potential applications of these silicate nanoplatelets in designing bioactive scaffolds for musculoskeletal tissue engineering.

Background: Langerhans cell histiocytosis (LCH) is a rare clonal malignancy of the monocyte-macrophage system. Patients with lesions in “risk organs” have significantly higher risk of mortality than patients with lesions limited to “non-risk” sites. The influence of early response to therapy on long-term survival in this heterogeneous multi-system disease was analyzed. Methods: During a 7-year period, we retrospectively analyzed the findings in 24 consecutive patients who required systemic chemotherapy for LCH [single system with multifocal bone involvement and multisystem involvement with or without risk organ (RO) involvement]. All patients were started on vinblastine and prednisolone. Progressive disease was treated with salvage protocols or targeted therapy. Positron emission tomography-computed tomography (PET-CT)/conventional CT based response assessment was performed at week 6 of chemotherapy, and if needed after week 12 of chemotherapy. Results: MFO bone, MS ROneg, and MS ROpos LCH was observed in 3, 4, and 17 patients, respectively. Age range of patients varied from 1 month–7 years (median = 18 months). The EFS and OS were 100% and 100% for MFO bone, 50% and 100%, respectively, for MS ROneg and 35% and 52%, respectively, for MS ROpos. OS was 93% and 100% for CR attained at 6 and 12 weeks respectively regardless of the risk status (P < 0.01). Conclusion: Rapid early response, that is, complete remission at 6 and 12 weeks was associated with significantly improved overall survival. In slow responders, early salvage with alternative regimens or targeted therapy may result in better outcomes.

Objectives: Acute Lymphoblastic Leukemia (ALL) in children presents with varied manifestations. At times, they may mimic symptoms and signs of Systemic onset Juvenile Idiopathic Arthritis (SoJIA). We analyzed children with ALL who were initially diagnosed as SoJIA thus leading to delay in diagnosis and treatment of ALL. Material and Methods: Retrospective study of records of 18 children diagnosed as ALL at our center between the period of January 2016 and December 2020, and who were initially diagnosed as SoJIA. Results: All 18 children presented with fever and joint pains involving large joints such as knee, ankle, wrist, and elbow. Seven (38.8%) cases had associated hepatosplenomegaly and three (16%) had lymphadenopathy at the time of presentation. Ten out of 18 children (55.6%) had normal peripheral complete blood counts. The duration from the time of onset of symptoms to diagnosis of ALL ranged from 15 days to 7 months in these cases. Four children had received steroids as treatment of SoJIA before they were diagnosed with ALL. Conclusion: Possibility of ALL must be ruled out in all cases suspected of having SoJIA, as leukemias may not always present with typical signs like hepatosplenomegaly, lymphadenopathy, or cytopenias. It will prevent delay in diagnosis and treatment of ALL. Administration of steroids to these patients for SoJIA, adversely affects post-ALL treatment outcomes.

Sitosterolemia is a rare autosomal recessive disease of plant sterol metabolism. Bhattacharyya and Connor first described this disease in 1974 [1]. To date, there are only about 100 known cases worldwide [2]. We describe two patients diagnosed with sitosterolemia at our center. Patient A is a 12-year-old male, presented with complaints of short stature, abdominal distension, and gradually progressive paleness since 2 months. He had pallor and hemolytic facies, and both weight (25 kg) and height (130 cm) were less than the 3rd centile and had spleno-hepatomegaly. His investigations (Table 1) were suggestive of a chronic hemolytic anemia. Since the child had giant platelets on peripheral smear and spherocytes were not seen, diagnosis of hereditary spherocytosis seemed unconvincing. So genetic work-up by next-generation sequencing (NGS) was done which revealed mutation in ABCG8 gene, suggestive of sitosterolemia. On review, his peripheral smear showed some stomatocytes (Fig. 1). Patient B is a 12-year-old child who was referred to us for splenectomy. The child had splenomegaly and bicytopenia, diagnosed during work-up for a short febrile illness. There were stomatocytes in his peripheral smear too, and sterol levels were borderline high (Table 2); hence, genetic studies were sent, which revealed compound heterozygous variants in the ABCG5 gene, suggestive of sitosterolemia type 2. Both patients belong to Asian background with no family history suggestive of an inherited red cell disorder. They are under regular follow-up for monitoring diet, counts, and changes of early atherosclerosis. If dietary changes are not adequate, we will consider ezetimibe for them.