Background and Aims:Chemotherapy with alternating cycles of vincristine-doxorubicin-cyclophosphamide and ifosfamide-etoposide, along with primary tumor treatment with surgery or radiotherapy or both, constitute the usual treatment of Ewing sarcoma. The AEWS0031 study demonstrated survival benefits after interval-compressed chemotherapy without significant toxicity. The aim of this study was to assess the tolerability of dose-intensified chemotherapy in developing countries like India.Methods:This was a retrospective analysis of children younger than 18 years of age with newly diagnosed Ewing sarcoma who came for treatment from December 2017 to December 2022. Children received vincristine (2 mg/m2), doxorubicin (75 mg/m2), and cyclophosphamide (1.2 g/m2) alternating with ifosfamide (9 g/m2), etoposide (500 mg/m2) for 17 cycles, with filgrastim (5 mu g/kg; maximum 300 mu g) between cycles. Primary tumor treatment was provided with surgery or radiotherapy or both. Local treatment was given between weeks 12 to 16. Toxicity was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. Radiologic response assessment was carried out with restaging CT or MRI scans after 6 to 8 cycles of chemotherapy in nonmetastatic and metastatic settings, respectively.Results:Thirty-one children were enrolled. Twenty-three children received all 17 cycles of chemotherapy. The median cycle interval was 18 days and 41% of children received chemotherapy at the 2-week interval. Grade 4 febrile neutropenia was observed in 32% of cycles but no treatment-related mortality was reported. Anemia and thrombocytopenia requiring transfusion support were recorded in 28 (5.6%) and 69 cycles (13.9%) of chemotherapy, respectively. There were 2 events of grade 4 cardiac toxicities in the form of cardiomyopathy and arrhythmia requiring intensive care management. After surgery, good necrosis was achieved in 61% of cases. Three children had a relapse with an event-free survival (EFS) of 87%.Conclusion:Intensified chemotherapy administered every 2 weeks intervals in Ewing sarcoma, is tolerable with adequate supportive care in resource-constrained settings.

Introduction Biallelic mismatch repair deficiency or constitutional mismatch repair deficiency (CMMRD) is a rare and aggressive pediatric cancer predisposition syndrome that occurs as a result of homozygous (biallelic) pathogenic variants in mismatch repair genes. The primary malignancies that occur in CMMRD are mainly hematological and brain malignancies. Most published data are from the western populations and the Middle East. Data from India are limited to case reports. We performed an analysis to determine the prevalence of CMMRD in the Indian population.

The survival rates for pediatric patients with primary refractory or high-risk relapsed B-cell acute lymphoblastic leukemia (r/r B-ALL), treated with chemotherapy-based protocols and followed by allogeneic hematopoietic cell transplantation (HCT), range from 15% to 30%.1 These outcomes are even more unfavorable in countries with evolving healthcare insurance systems due to treatment-related mortality and financial toxicity.2 The long-term event-free survival for such high-risk relapse of B-ALL is dependent on achieving minimal residual disease (MRD) negativity prior to HCT.3 In the past decade, there have been significant advancements in targeted antibody-based immunotherapies for managing r/r B-ALL.4-11 Blinatumomab (Blina) is a T-cell engager that provides an antileukemic effect by targeting cytotoxic T cells to CD19-expressing cancer cells. Several studies have revealed the excellent efficacy of Blina in low-burden disease.4-8 However, recipients of Blina with high tumor burden have low response rates and are at risk of severe cytokine release syndrome (CRS).9 Whereas, Inotuzumab ozogamicin (InO) targets CD22, which is conjugated to calicheamicin, a potent cytotoxic agent and works well even for high-burden disease with response rates as high as 80%.10, 11 To optimize the use of these novel immunotherapies in r/r B-cell ALL, we designed a disease-burden-adapted protocol of InO followed by Blina for high-burden (minimal residual disease (MRD) > 5%) CD22+ CD19+ disease and Blina only for low-burden (MRD ≤ 5%) CD19+ disease. This is a retrospective analysis of 39 patients with r/r B-cell ALL patients aged 1–18 years treated in three centers from January 2018 to August 2023. Patients were treated with a chemotherapy-based protocol from January 2018 to April 2021 and on a disease-burden-adapted immunotherapy protocol from May 2021 to August 2023. End-of-induction (EOI) MRD of >5% with high-risk cytogenetics or age >16 years and all patients with end-of-consolidation (EOC) MRD > 0.1% irrespective of age or cytogenetics were considered primary refractory. Very early relapse (<18 months from diagnosis; marrow or isolated extramedullary), early relapse (18–36 months from diagnosis or until 6 months off therapy; marrow or isolated extramedullary), and late relapse (≥36 months from diagnosis or >6 months off therapy; marrow or isolated extramedullary) with postrelapse induction MRD of ≥0.1% and second relapse with any level of disease were considered as high-risk. A fractionated dose of InO as 1.8 mg/m2 per course was administered intravenously over 1 h on Days 1, 8, and 15 of 28-day cycle as previously described.10, 11 Blina was given as a 28-day continuous intravenous infusion. The first 7 days of the first cycle were administered at 5 mcg/m2/day, and subsequently, the dose was increased to the maximum tolerated dose, up to a maximum of 15 mcg/m2/day. Flow cytometric immunophenotypic analysis of the bone marrow was done on CD45/side scatter plots for diagnosis and follow-up MRD. In view of Blina and InO therapy, previously described alternate gating strategies were used.12 Bone marrow MRD assessments were conducted after each course of immunotherapy and after HCT at 1-, 2-, 3-, 6-, and 12-month intervals. Treatment responses were classified as complete response if MRD was negative, good response if MRD was detectable to less than 0.01%, partial response if the disease burden reduced but was more than 0.01%, and no response or progressive disease depending on whether the disease burden was stable or progressive. Patients were followed up in the clinic until November 2023. Adverse events including neurotoxicity, cytokine release syndrome, veno-occlusive disease (VOD), and tumor lysis syndrome were graded using the CTCAE, version 5. Overall survival was measured as time from immunotherapy to death, and event-free survival was measured as time from immunotherapy to relapse or death. We also compared the overall survival of high-risk relapsed leukemia patients in the cohort who received immunotherapy with that of high-risk relapsed leukemia patients from January 2018 to April 2021, predating the immunotherapy protocol. The Kaplan–Meier method was used to generate survival curves. This analysis was performed in line with the principles of the Declaration of Helsinki. Bai Jerbai Wadia Hospital Ethics Committee approved retrospective analysis (Ethics No. IEC/BJWHC/AP/2024/025). Nineteen consecutive patients with r/r B-cell ALL were treated with the disease-burden-adapted immunotherapy protocol from May 2021 to August 2023. All patients were consented for immunotherapy. The median age of the cohort was 12 years (range: 2–17 years), and two-thirds of patients were ≥10 years of age. Five were females and 14 were males. Seven patients had high-risk cytogenetics (three low hypodiploidy and one each of ABL1, iAMP21, IKZF1 deletion, and MLL-rearrangement). The demographic, leukemia characteristics, and treatment details of patients are shown in Table 1. Eight patients were primary refractory (4 = induction failure, 4 = consolidation failure). All primary refractory patients were referred from different hospitals across the country. Eleven patients had high-risk relapsed leukemia (2 = very early, 4 = early relapse, 2 = late relapse with post-relapse induction MRD of ≥0.1%, 3 = second relapse). Patients with relapsed leukemia received either three previous chemotherapy protocols (n = 5), two previous chemotherapy protocols (n = 5), or one previous chemotherapy protocol (n = 1). Ten patients received chemotherapy-based relapse induction for the latest relapse, and all had postinduction residual disease. Five of 19 patients (26%) had an extramedullary disease, three were central nervous system positive, and two had testicular involvement. Twelve patients (5 = primary refractory; 7 = relapsed) with MRD ranging from 0.008% to 4.21% received Blina alone (Figure 1A). The median number of Blina cycles was 2 (range: 1–3). All 12 patients achieved MRD-negative remission after the first cycle. Seven patients (3 = primary refractory; 4 = relapsed) with high-burden disease ranging from 5.34% to 78% received one cycle of InO (Figure 1A). Six patients responded to InO; three patients became MRD-negative, and three patients achieved a good response. All six patients received consolidation with Blina and achieved MRD-negative status. One patient progressed on InO and, as a result, received palliative care. Eighteen patients (95%) achieved MRD-negative status with the disease-burden-adapted protocol. Sixteen patients (84%) have undergone allogeneic HCT. Seven patients received grafts from haploidentical donors, six underwent matched unrelated donor HCT, and three received HCT from matched sibling donors. One patient, lacking an HLA-matched donor, underwent an autologous transplant due to high-risk pretransplant factors, such as chronic parvoviremia, intestinal adenovirus shedding, and obesity. Another patient, also without an HLA-matched donor, chose maintenance chemotherapy because of chronic parvoviremia and intestinal adenovirus shedding. Fifteen patients (77%; 95% CI: 49.5–90.6) were alive and in continuous MRD-negative CR with a median postimmunotherapy follow-up of 424 days (range: 117–914; Figure 1B,C). Nine (82%) of 11 patients who received disease-burden-adapted protocol for relapsed leukemia were disease-free at a median follow-up of 317 days (range: 117–853). In contrast, one of 20 patients (5%) were disease-free in the preimmunotherapy high-risk relapsed leukemia cohort with a median survival of 93 days (Figure 1D; p < 0.0001). The comparison of the preimmunotherapy cohort versus the cohort treated with disease-burden-adapted protocol is shown in Supporting Information S1: Figure 1. Nine (50%) patients developed mild CRS with Blina (7 = grade 1, 2 = grade 2). Two (12%) patients experienced grade 1 neurotoxicity that recovered after transient discontinuation of Blina. One patient treated with InO had grade 1 CRS. Six patients who received InO have undergone HCT to date and only one experienced mild VOD during HCT, which responded to fluid restriction and diuretics. No patients experienced immunotherapy-related grade 3 or grade 4 toxicity. There were four deaths in the immunotherapy cohort. The causes of death included disease progression on InO in one patient, post-HCT CD19-negative relapse in another patient, and the other two patients succumbed to transplant-related mortality; one died of acute respiratory distress syndrome and another patient succumbed to early disseminated adenoviremia. Patients diagnosed with refractory ALL inherently exhibit resistance to chemotherapy and those with relapsed ALL acquire resistance during chemotherapy exposure.13 The alternative mechanism of targeting B-cell antigens with antibody-based immunotherapies provides greater opportunities for precision medicine. Clinical trials have shown that using Blina as a bridging regimen before HCT for relapsed B-cell ALL can improve disease-free survival rates.4-8 At a median follow-up of 2 years, the disease-free survival rates for patients who received Blina ranged from 55% to 65%.4, 8 The observations that Blina works better in the MRD setting than in hematological remission, and up to 80% of patients with high tumor burden respond to InO, formed the basis of the protocol.4-11 Notably, no serious side effects were observed in this protocol. Our protocol of consolidating InO response with Blina may also reduce the risk of VOD by allowing more time between InO administration and transplant. Furthermore, exclusive use of Blina in low-burden disease could have abrogated the risk of severe CRS or neurotoxicity. In parallel to the development of antibody-based immunotherapies, advances in cell-based immunotherapies have occurred.14, 15 Cell-based immunotherapies require significant laboratory expertise and are expensive. In addition, at least 50% of patients relapse after CAR T-cell therapies and not all CAR T-cell therapies yield similar results.14, 16, 17 Allogeneic HCT as a consolidative therapy after CAR T cells offsets the potential benefits of autologous CAR T cells. In contrast, antibody-based therapies are off-the-shelf, manufacture-controlled, and do not require infrastructure, making them a more viable option in regions with emerging healthcare insurance systems. To conclude, the disease-burden-adapted protocol is a promising strategy for treating r/r pediatric B-ALL as a bridging regimen before HCT. The report underscores the importance of making these immunotherapies accessible on a global scale through collaborative efforts involving governments, nongovernmental organizations, and pharmaceutical initiatives. While the analysis is retrospective, its findings highlight the efficacy and safety of this strategy allowing a greater number of patients to reach potentially curative HCT. We acknowledge Amgen's Blincyto Humanitarian compassionate access program that helped to treat patients with relapsed-refractory B-cell acute lymphoblastic leukemia. Prashant Hiwarkar conceived the study and analyzed the data. Sanaa Khan, Krishnan VP, Lashkari Harshaprasad, and Purva Kanvinde acquired the data. Sanaa Khan, Krishnan VP, and Prashant Hiwarkar wrote the manuscript. Kunal Sehgal did flow cytometry analysis. Sanaa Khan, Krishnan VP, Yamini Krishnan, Gazel Sainulabdin, Somdipa Pal, Rincy Mathews, Darshan Kataria, Minnie Bodhanwala, Bharat Agarwal, Ambreen Pandrowala, and Prashant Hiwarkar were actively involved in patient care; all authors revised and approved the final manuscript. The authors declare no conflict of interest. This research received no funding. The data sets generated and/or analyzed during the current study are not publicly available because patients and/or legal guardians have not consented to data sharing but are available from the corresponding author upon reasonable request. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Chronic recurrent multifocal osteomyelitis (CRMO), also known as chronic non-bacterial osteomyelitis (CNO), is an autoimmune inflammatory bone disorder mainly affecting children and adolescents. The clinical presentation varies from mild, self-limiting unifocal bone inflammation, which is more common, to multifocal recurrent disease. CRMO can be misdiagnosed as multifocal bone Langerhans cell histiocytosis (LCH), infections, lymphoma, or metabolic bone disease. Clinical features are highly variable and not very specific. Most children experience vague aches and pains over prolonged periods but remain generally well and do not exhibit growth failure. In this article, we describe a case series of three children who presented with multifocal bone disease and were initially referred for LCH; however, detailed investigations confirmed the diagnosis of CRMO. The treatment options included non-steroidal anti-inflammatory drugs, corticosteroids, and disease-modifying anti-rheumatic drugs. Other treatment options included anti-tumor necrosis factor agents and bisphosphonates, similar to those used for autoimmune bone diseases. CRMO should be considered a differential diagnosis in children presenting with chronic, vague, and recurrent bony symptoms with or without systemic symptoms.

Background: Primary malignancies of the thyroid gland are less frequent in the first two decades of life and accounts for only 0.5-3% of all malignant neoplasms in children and adolescents.Methods: A retrospective analysis was undertaken on children less than 18 years of age who were diagnosed with thyroid malignancy from 1st June 2018 to 31st May 2022. The electronic health records were reviewed to determine patient demographics, pathological characteristics, interventions (surgery and radioactive iodine therapy [RAI]) and follow up.Results: Eighteen patients were less than 18 years of age at the time of diagnosis. Mean age at diagnosis was 14.7 years (6-18 years). Majority were females and in post pubertal age group. Among our cohort 83.4% had stage 1 disease, whereas 16.6% had stage II disease. Lung involvement was noted in 16.6%. Risk stratification revealed that 44.6% of the children were in the high-risk group and 38.8% in the intermediate- risk group. Fifteen patients (83.3%) underwent I-131 therapy. Follow up period ranged from 2-51.7 months with a median follow up period of 22.15 months. Complete remission was noted in 15 patients (83.3%). Out of the children with metastatic lung disease, 1 had progressive disease, 2 had stable disease. Overall survival was 100%.Conclusion: Majority of our children in our retrospective data presented with nodal and distant metastasis. With the current advances in the treatment of thyroid malignancies, a good survival was noted even in children with pulmonary metastasis.

Science and technology are in a rapid development stage as a result of the advancement and progress of the times, and it is clear that the contemporary civilization has entered the era of Artificial Intelligence (AI). This research focuses on AI applications in the context of Industry 4.0 concept. This current work discusses AI acceptance in the manufacturing industry and its promotion in intelligence optimization. The Virtual model concept is presented to improve the rationale of various interfaces. The communication and information intelligence AI algorithms are examined in depth. The concept of a smart city and AI applications, as well as how AI plays a role in its implementation have been discussed.

Pediatric Blood & CancerVolume 70, Issue 6 e30252 LETTER TO THE EDITOR Somatic CBL mutation presenting as juvenile myelomonocytic leukemia with vasculitis Varsha Mishra, Varsha Mishra Department of Blood and Marrow Transplantation, Bai Jerbai Wadia Hospital for Children, Mumbai, IndiaSearch for more papers by this authorV. P. Krishnan, V. P. Krishnan orcid.org/0000-0003-4469-6866 Department of Blood and Marrow Transplantation, Bai Jerbai Wadia Hospital for Children, Mumbai, IndiaSearch for more papers by this authorMukesh Desai, Mukesh Desai Department of Inborn errors of Immunity, Bai Jerbai Wadia Hospital for Children, Mumbai, IndiaSearch for more papers by this authorHirva Manek, Hirva Manek Department of Radiology, Bai Jerbai Wadia Hospital for Children, Mumbai, IndiaSearch for more papers by this authorAmbreen Pandrowala, Ambreen Pandrowala Department of Blood and Marrow Transplantation, Bai Jerbai Wadia Hospital for Children, Mumbai, IndiaSearch for more papers by this authorMinnie Bodhanwala, Minnie Bodhanwala orcid.org/0000-0002-3301-3858 Department of Pediatrics, Bai Jerbai Wadia Hospital for Children, Mumbai, IndiaSearch for more papers by this authorPrashant Hiwarkar, Corresponding Author Prashant Hiwarkar [email protected] Department of Blood and Marrow Transplantation, Bai Jerbai Wadia Hospital for Children, Mumbai, India Correspondence Prashant Hiwarkar, Department of Blood and Marrow transplantation, Bai Jerbai Wadia Hospital for Children, Mumbai 400012, India. Email: [email protected]Search for more papers by this author Varsha Mishra, Varsha Mishra Department of Blood and Marrow Transplantation, Bai Jerbai Wadia Hospital for Children, Mumbai, IndiaSearch for more papers by this authorV. P. Krishnan, V. P. Krishnan orcid.org/0000-0003-4469-6866 Department of Blood and Marrow Transplantation, Bai Jerbai Wadia Hospital for Children, Mumbai, IndiaSearch for more papers by this authorMukesh Desai, Mukesh Desai Department of Inborn errors of Immunity, Bai Jerbai Wadia Hospital for Children, Mumbai, IndiaSearch for more papers by this authorHirva Manek, Hirva Manek Department of Radiology, Bai Jerbai Wadia Hospital for Children, Mumbai, IndiaSearch for more papers by this authorAmbreen Pandrowala, Ambreen Pandrowala Department of Blood and Marrow Transplantation, Bai Jerbai Wadia Hospital for Children, Mumbai, IndiaSearch for more papers by this authorMinnie Bodhanwala, Minnie Bodhanwala orcid.org/0000-0002-3301-3858 Department of Pediatrics, Bai Jerbai Wadia Hospital for Children, Mumbai, IndiaSearch for more papers by this authorPrashant Hiwarkar, Corresponding Author Prashant Hiwarkar [email protected] Department of Blood and Marrow Transplantation, Bai Jerbai Wadia Hospital for Children, Mumbai, India Correspondence Prashant Hiwarkar, Department of Blood and Marrow transplantation, Bai Jerbai Wadia Hospital for Children, Mumbai 400012, India. Email: [email protected]Search for more papers by this author First published: 14 February 2023 https://doi.org/10.1002/pbc.30252Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. REFERENCES 1Aoki Y, Matsubara Y. Ras/MAPK syndromes and childhood hemato-oncological diseases. Int J Hematol. 2013; 97(1): 30-36. 10.1007/s12185-012-1239-y CASPubMedWeb of Science®Google Scholar 2Lipka DB, Witte T, Toth R, et al. RAS-pathway mutation patterns define epigenetic subclasses in juvenile myelomonocytic leukemia. Nat Commun. 2017; 8(1): 2126. 10.1038/s41467-017-02177-w PubMedWeb of Science®Google Scholar 3Hecht A, Meyer JA, Behnert A, et al. Molecular and phenotypic diversity of CBL-mutated juvenile myelomonocytic leukemia. Haematologica. 2022; 107(1): 178-186. 10.3324/haematol.2020.270595 CASPubMedWeb of Science®Google Scholar 4Caye A, Strullu M, Guidez F, et al. Juvenile myelomonocytic leukemia displays mutations in components of the RAS pathway and the PRC2 network. Nat Genet. 2015; 47(11): 1334-1340. 10.1038/ng.3420 CASPubMedWeb of Science®Google Scholar 5Becker H, Yoshida K, Blagitko-Dorfs N, et al. Tracing the development of acute myeloid leukemia in CBL syndrome. Blood. 2014; 123(12): 1883-1886. 10.1182/blood-2013-10-533844 CASPubMedWeb of Science®Google Scholar 6Seaby EG, Gilbert RD, Andreoletti G, et al. Unexpected findings in a child with atypical hemolytic uremic syndrome: an example of how genomics is changing the clinical diagnostic paradigm. Front Pediatr. 2017; 5: 113. 10.3389/fped.2017.00113 PubMedWeb of Science®Google Scholar 7Saettini F, Coliva TA, Vendemini F, et al. Abnormal B-cell maturation and increased transitional B cells in CBL syndrome. Front Pediatr. 2022; 10:935951. 10.3389/fped.2022.935951 PubMedWeb of Science®Google Scholar 8Locatelli F, Niemeyer CM. How I treat juvenile myelomonocytic leukemia (JMML). Blood. 2015; 125(7): 1083-1090. 10.1182/blood-2014-08-550483 CASPubMedWeb of Science®Google Scholar Volume70, Issue6June 2023e30252 ReferencesRelatedInformation

Background Transplantation-associated thrombotic microangiopathy (TA-TMA) is an endothelial injury syndrome linked to the overactivation of complement pathways. It manifests with microangiopathic hemolytic anemia, consumptive thrombocytopenia, and microvascular thrombosis leading to ischemic tissue injury. Mannose residues on fungi and viruses activate the mannose-binding lectin complement pathway, and hence activation of the lectin pathway could be one of the reasons for triggering TA-TMA. Narsoplimab, a human monoclonal antibody targeting MASP-2 is a potent inhibitor of the lectin pathway. We describe the transplant course of a pediatric patient who developed TA-TMA following Candida-triggered macrophage activation syndrome and was treated with Narsoplimab. The data collection was performed prospectively. Case presentation The six-year-old girl underwent a human leucocyte antigen (HLA) haploidentical hematopoietic stem cell transplant using post-transplant Cyclophosphamide for severe aplastic anemia. In the second week of the transplant, the patient developed macrophage activation syndrome necessitating treatment with steroids and intravenous immunoglobulin. Subsequently, USG abdomen and blood fungal PCR revealed the diagnosis of hepatosplenic candidiasis. Candida-triggered macrophage activation syndrome responded to antifungals, steroids, intravenous immunoglobulin, and alemtuzumab. However, the subsequent clinical course was complicated by thrombotic microangiopathy. The patient developed hypertension in the 2nd week, followed by high lactate dehydrogenase (1010 U/L), schistocytes (5 per hpf), low haptoglobin (< 5 mg/dl), thrombocytopenia, and anemia in the 3rd week. Ciclosporin was stopped, and the patient was treated with 10 days of defibrotide without response. The course was further complicated by the involvement of the gastrointestinal tract and kidneys. She had per rectal bleeding with frequent but low-volume stools, severe abdominal pain, and hypoalbuminemia with a rising urine protein:creatinine ratio. Narsoplimab was started in the 5th week of the transplant. A fall in lactate dehydrogenase was observed after starting Narsoplimab. This was followed by the resolution of gastrointestinal symptoms, proteinuria, and recovery of cytopenia. The second episode of TA-TMA occurred with parvoviraemia and was also successfully treated with Narsoplimab. Conclusion Lectin pathway inhibition could be useful in treating the fatal complication of transplant-associated thrombotic microangiopathy.

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.

Immature platelet fraction (IPF) is a quantification of immature platelets in the circulation reflecting the state of thrombopoiesis in the marrow. Normal reference range for IPF has been established in adults. Reference intervals in neonates are highly dependent on gestational age of the neonate. Complete blood counts (CBC) with IPF of all neonates admitted in neonatal intensive care unit (NICU) were analyzed using Mindray BC-6800 Auto Hematology analyzer. Platelet count of less than 150 × 10^9/L was assigned as thrombocytopenia. Neonates were divided into four groups as per the corrected gestational age (CGA) on the day of CBC analysis: 28–32 weeks, 32–34 weeks, 34–37 weeks, and >37 weeks according to World Health Organization (WHO) classification. Mean, standard deviation, and 95% confidence interval for IPF was calculated in each group and reference range for IPF was derived. Mean IPF in neonates with normal platelet count was term––3.58 (95% CI 3.29 to 3.87), late preterm Neonates (34–37 weeks)––4.14 (95% CI 3.82 to 5.0), moderate preterm neonates (32–34 weeks)––4.14 (95% CI 3.46 to 4.82), and in Very Preterm neonates (28–32 weeks)––IPF of 5.51 (95% CI 3.95 to 7.07). We aimed to establish a reference range for IPF in neonates of different gestational age groups. The IPF values in neonates were comparable between hematology analyzers in neonates with normal platelet counts.