Posterior Mediastinal Tumor Presenting With Compressive Myelopathy- Uncommon Site For A Rare Tumor Mohanaraj Ramachandran, Padmalatha Kadamba, Namita Ravikumar, Komal Chippalkatti, Rama Mohan Reddy, Harisha Karibasappa, Dinesh Raju, Arjun Srivatsa, Sai Prasad TR, Prasad Narayanan, Harish Pathalingappa

Letters to the editorSomato-cognitive coordination therapy in a brain tumor survivor with attention-deficit/hyperactivity disorder symptoms and motor coordination impairmentsMasanobu Takeuchi, MD, PhD 1，Ayumi Kato, MD, PhD2，Masahiko Hara, MD, PhD 3Department of Pediatrics, Yokohama City University Hospital, Yokohama, JapanDepartment of Diagnostic Radiology, Yokohama City University Hospital, Yokohama, JapanDepartment of Neurology and Clinical Rehabilitation, mediVR Rehabilitation Center Tokyo, Tokyo, JapanCorrespondenceMasanobu Takeuchi3-9 Fukuura, Kanazawa, Yokohama, Kanagawa 236-0004, JapanPhone: (+81)-45-787-2800Fax: (+81)-45-787-2800mtake@yokohama-cu.ac.jpTotal Word counts: 831 wordsFigure: 1 FigureReference: 10 ReferencesKey words: Somato-cognitive coordination therapy, Attention-deficit/hyperactivity disorder, brain tumor survivor, cerebral blood flow

Since 2000, centers across Central America have shared treatment guidelines for Wilms tumor, using histology (anaplasia present or absent) and tumor stage to stratify patients into low, intermediate, and high-risk groups. Weekly virtual tumor board meetings involving local and international experts were held to ensure consistent treatment assignments. We analyzed data from 367 children with unilateral tumor treated per these guidelines. Five-year abandonment-sensitive event-free and overall survival estimates were: low-risk 82% ±3.8% and 86% ±3.6%, intermediate-risk 50% ±3.4% and 60% ±3.4%, and high-risk 36% ±7.6% and 45% ±7.9%. Survival outcomes were suboptimal, primarily due to advanced disease in fragile children at presentation and abandonment of treatment.

TITLE: Clinical Improvement without Increased Platelet Count with Eltrombopag in X-Linked ThrombocytopeniaAuthors:Mahmut Yasar Çeliker (Corresponding author)Director of Pediatric Oncology ProgramDivision of Pediatric Hematology and Oncology Department of Pediatrics Maimonides Children’s Hospital 977 48th Street, Brooklyn, NY, 11219Phone: +1 718-283-6652Fax: +1 718-635-5973Email: Mceliker@maimo.orgAbena Odurowaa YeboahDepartment of Pediatrics Maimonides Children’s Hospital 977 48th Street, Brooklyn, NY, 11219Ludovico GuariniPediatric Hematology and Oncology Division of Pediatric Hematology and Oncology Department of Pediatrics Maimonides Children’s Hospital 977 48th Street, Brooklyn, NY, 11219

A document by Mohanaraj Ramachandran. Click on the document to view its contents.

Background: Surgery remains the cornerstone of treatment for rhabdomyosarcoma (RMS) in children. However, there is considerable variation in surgical management practices worldwide, highlighting the need for standardized clinical practice guidelines (CPG). Methods: The CPG development involved assembling a multidisciplinary group, prioritizing ten key topic areas, conducting evidence searches, and synthesizing findings. Recommendations were voted on using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) methodology. Recommendations: The panel recommended regional lymph node evaluation for patients with paratesticular RMS who are more than 10 years old and extremity RMS. Other suggestions included pre-treatment re-excision for incompletely resected RMS, preoperative radiation therapy for unresectable tumors, maintaining a 0.5 cm resection margin, and tumor bed marking with surgical clips. The panel also suggests resection of residual metastatic disease following chemotherapy, resection of relapsed disease, and the least invasive approach for managing patients presenting with obstruction. Conclusion: This CPG provides evidence-based surgical management recommendations for RMS that can be adapted to diverse resource settings.

Harlequin syndrome is characterized as ipsilateral loss of vasomotor and sudomotor function with contralateral hyperhidrosis and flushing in response to heat, exercise, or emotional stimuli caused by disruption to the sympathetic cervical chain. Here, we present a case of Harlequin syndrome in a 1-year-old male with subsequent identification of paraspinal neuroblastoma. Though Horner syndrome, another form of dysautonomia, has been associated with neuroblastoma, this is the first documentation of Harlequin syndrome with neuroblastoma in the English medical literature. Familiarity with the underlying anatomy and pathophysiology should be understood to prevent misdiagnosis in patients with potential early signs of neuroblastoma.

Background And Aims: Invasive fungal infections (IFI) in children with newly diagnosed acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) are poorly characterized, especially in lower-middle income countries (LMICs). This study aims to identify the incidence, risk factors and outcomes of IFI in a pediatric cohort with ALL/LBL. Methods: We retrospectively analysed pediatric patients diagnosed with ALL/LBL between January and December 2023 at a tertiary cancer center in India. Patients were risk-stratified and treated per the modified ICiCLe protocol. IFIs were classified as proven, probable and possible according to the revised EORTC/MSG consensus definition. Results: Among 407 patients, 392 (96%) had ALL. The overall incidence of IFI was 24%, with probable/proven infections in 12%. Mold infections predominated (79 cases, 77%), followed by yeast infections (21 cases, 21%). In comparison to patients without IFIs, those with IFIs were more likely to have received dexamethasone (30% vs 20%; p=0.009) and anthracycline (28% vs 14%; p=0.001) during induction. Chemotherapy interruptions occurred in 56% of IFI cases, impacting treatment continuity. The 6-week mortality rate of patients with IFI was 15%, rising to 26% in probable/proven cases. Coexisting bacterial infection was associated with increased mortality (odds ratio: 19.2[95%CI: 3.5-105]; p=0.001). Conclusion: IFIs are common in newly diagnosed ALL/LBL patients in LMICs, particularly during early phases of therapy. These infections are associated with considerable mortality, often compounded by concomitant bacterial sepsis. Given these findings, consideration of antifungal prophylaxis is warranted to mitigate morbidity and mortality due to IFIs.

Background: Thrombopoietin receptor agonists (TPO-RAs) have demonstrated efficacy in treating clinically significant thrombocytopenia, including chemotherapy-induced thrombocytopenia (CIT) in adults. However, data regarding their safety and efficacy in pediatric, adolescents, and young adult (AYA) patients with hematologic malignancies are limited. Methods: We retrospectively identified 15 pediatric and AYA patients aged 25 years or younger with hematologic malignancies treated with a TPO-RA at UCSF Benioff Children’s Hospitals between 2015 and 2023. Platelet counts and transfusion requirements were compared before and after TPO-RA therapy. Results: The median age at TPO-RA initiation was 16 years (range: 7-25 years). Nine patients (60%) had a history of bleeding or comorbidity that predisposed to severe bleeding risk. Eleven patients received romiplostim and four patients received eltrombopag. The median platelet count significantly increased from 24 x 10 9/L at baseline to 54 x 10 9/L after 3 weeks of any TPO-RA therapy (p =0.029). Monthly platelet transfusion requirements significantly decreased from a median of 15 to two units after TPO-RA therapy (p=0.007). Fourteen of the 15 patients (93%) achieved a sustained platelet count >50,000/µL within eight weeks, with a median time to response of 3 weeks. No TPO-RA-related adverse events were observed. Conclusion: TPO-RAs were effective in managing refractory thrombocytopenia in pediatric and young adult patients being treated for hematologic malignancies, with a favorable safety profile, even among patients with multiple comorbidities. These findings warrant further investigation through prospective clinical trials to confirm efficacy and establish clinical guidelines for this population.

Systemic Inflammatory Response Post Alemtuzumab and Low-Dose Total Body Irradiation in Pediatric Patients with Sickle Cell Disease: A Case SeriesRozalyn Chok1, Katherine Girgulis2, Robert S Nickel3,4, Gregory MT Guilcher2*.Division of Hematology, Oncology, Stem Cell Transplantation, and Regenerative Medicine, Lucile Packard Children’s Hospital, Stanford University, Stanford, California, United States.Section of Oncology/BMT, Alberta Children’s Hospital, University of Calgary, Calgary, Alberta, Canada.Division of Hematology and Division of Blood and Marrow Transplantation, Children’s National Hospital, Washington, District of Columbia, United States.Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, United States.*Correspondence to:Gregory Guilcher, MD, Section of Oncology/BMT, University of Calgary, Alberta Children’s Hospital, 28 Oki Drive Trail NW, Calgary, AB, T3B 6A8. Email: greg.guilcher@ahs.caText word count: 786 wordsRunning title: SIRS Post TBI in SCD PatientsKeywords: Sickle Cell Disease, Total Body Irradiation, Alemtuzumab, Hematopoietic Stem Cell TransplantFigures: 0Tables: 2

A document by Summer Xu. Click on the document to view its contents.

Introduction: Leptomeningeal disease (LMD) in diffuse midline gliomas can lead to devastating symptoms such as severe pain, urinary incontinence, and tetraparesis, with limited treatment options. In the present study, we determined whether the detection of H3F3A K27M-mutant droplets in cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) could serve as a reliable biomarker for the detection of LMD in diffuse midline gliomas. Methods: Twenty-four CSF samples were obtained from 21 diffuse midline glioma patients. Histological confirmation of H3F3A K27M mutation was obtained in 9 (42.8%) cases. ctDNA was extracted from CSF, and H3F3A K27M-mutant and wildtype droplets were detected using digital droplet PCR (ddPCR). LMD was diagnosed by CSF cytology and/or pre- and post-contrast head and whole spine MR imaging. Results: The number of H3F3A K27M-mutant droplets (median 7 [range 0-297] vs median 0 [range 0-2]; p <.0001) and variant allele frequency (VAF) (median 50.0% [range 7.5-87.5%] vs median 0.0% [range 0.0-40.0%]; p <.0001)) were significantly higher in the LMD/early LMD group compared to no LMD group. In two cases (Case 4 and Case 11) without clinical evidence of LMD, multiple H3F3A K27M-mutant droplets were detected in the CSF ctDNA. In those cases, extensive spinal dissemination was detected 175 and 176 days after the initial liquid biopsy. One case (Case 15) with high Schlafen11 (SLFN11) expression in the tumor responded well to treatment for LMD and survived for 532 days after the diagnosis of LMD. Conclusion: This study provides evidence that detecting H3F3A K27M-mutant droplets in CSF ctDNA is diagnostic for LMD and is more sensitive than traditional methods such as CSF cytology and MR imaging.

Clinical Relapse versus Treatment failureThe case for surveillance for reappearance of minimal measurable disease in pediatric patients with higher risk B-ALL.Paul S. Gaynon1 and Linwei Li21. University of Southern California, Keck School of Medicine, Los Angeles CA 900892. University of Texas, Rio Grande Valley School of Medicine, Edinburg, TX 78541Despite impressive progress in childhood acute lymphoblastic leukemia, an urgent clinical need remains. Patients still relapse and outcomes after relapse have changed little between 1996- 2006 and 2004 – 2014.1 Despite progress with late marrow relapse (1st remission (CR1) > 36 months), treatment of early relapse (CR1 < 36 months) remains unsatisfactory,2 especially in patients deemed higher risk at diagnosis, such as adolescents and young adults (AYA’s).3Progress to date derives from improved primary therapy. Further improvements in primary therapy have an ever-increasing price. Going from 50% to 70%, a 40% reduction in relapses, 5 patients need to be treated to prevent one relapse. Similarly, going from 75% to 85%, again a 40% reduction relapses, 10 patients need to be treated to prevent one relapse. With improving outcomes with primary therapy, we are facing an increasing number needed to treat for further improvement.4 All patients need to bear the burden of a novel intervention to benefit an ever smaller percentage. Not all interventions are successful.Recent experience suggests that we are reaching the limits of “intensification” of therapy, despite improvements in supportive care.5 For some patients such AYA’s, we may have surpassed tolerable limits. Querying the Pediatric Health Information system database, Gupta et al found a higher incidence of intensive care unit stays and increased toxicities in almost every organ system for AYA’s.6 Serious complications may prevent delivery of best care, resulting in relapse.Personalized molecularly targeted medicine is complicated by the vast interpatient diversity of ALL7 and intra-patient oligoclonality.8 Inhibition of a single driver pathway is unlikely sufficient for cure.9We have, however, newer modalities, such as inotuzumab,10,11 blinatumomab,12,13and chimeric antigen re-arranged (CAR) T-cells14,15that target large subsets of B-ALL. Blinatumomab has demonstrated value in relapsed B-ALL.12,13 Emerging experience has shown that blinatumomab and CAR T-cells work better at lower disease burdens.14-17 In 2017, blinatumomab was licensed for children and adults with B-ALL in 1st or second remission with measurable residual disease > 0.1%.18The presence of 25% marrow lymphoblasts blasts has long been the threshold for clinical marrow relapse. 19 Earlier reports showed that early detection of overt clinical relapse provides no clinical benefit.20,21 However, treatment fails, i.e., blast proliferation exceeds blast kill, prior to clinical relapse. We now have reliable technologies to identify low levels of re-appearing leukemia.22 Serial assessment of MRD and prompt intervention has yet to be tested systematically.In B-ALL, flow cytometry has largely overcome our inability to distinguish lymphoblasts from hematogones and recovery myeloblasts. Current flow cytometric or polymerase chain reaction technologies allows reliable detection of re-appearing lymphoblasts at levels 2 log10 below 1%.22 Next generation sequencing (NGS) allows detection 4 log10 below 1% and restaging of some patients called mistakenly classified MRD positive because of low numbers of low specificity targets.23 A new international consensus proposes that the confirmed presence of 1% lymphoblasts after the third month of therapy constitutes relapse or induction failure, if not preceded by a remission.24Flow cytometry, PCR, NGS, FISH, cytogenetics, and /or RT-PCR when relevant may be employed.Reappearance of MRD greater than some number predicts relapse in adult25 and pediatric trials.26Cheng et al report that reappearance of MRD reliably predicted relapse in their 30 patient cohort.27Early intervention may have clinical value. Wang et al reported on 1030 children who achieved MRD negative remission. One hundred fifty had MRD reappearance at a median time of 11 months. At 5 years, the EFS was 88.5% for continuously negative MRD and 38.4% for reemergent MRD. Eighty-five MRD reemergent patients subsequently relapsed at a median of 4.1 months. Reappearance of MRD was the most powerful adverse prognostic factor in multivariate analyses. An MRD cutoff of 0.15% gave the best discrimination. After reemergent MRD, 113 continued chemotherapy at their families’ choice and 37 underwent HSCT in CR1. The 2-year overall survival was 89% for HSCT and 46% for continued chemotherapy (p< 0.001); the cumulative incidence of relapse was 23% and 64% (p< 0.001).28MRD surveillance is not yet standard in pediatric ALL. However, MRD surveillance is already included in adult ALL guidelines.29,30 “Bone marrow aspirate can be considered as clinically indicated at a frequency of up to 3 to 6 months for at least 5 years.” 30In the past marrow sampling has been required as marrow and peripheral blood are unpredictably discordant in B-ALL. 31 Marrow aspiration is painful, and children often receive anesthesia. Marrow aspirates include a variable proportion of peripheral blood affecting the precision of MRD estimates. NGS may allow peripheral blood sampling.NGS has further lowered the limits of quantification to 10-6 and raised the possibility of peripheral blood monitoring in B-ALL.31 Rau et al found that end induction peripheral blood (PB) NGS was positive in nearly all cases marrow MRD by flow was positive at 0.01%. Muffly et al found that clinical relapse followed reappearance of peripheral blood NGS with a median of 90 days after HSCT and 60 days following CAR T therapy. Peripheral blood NGS surveillance of higher risk B-ALL patients seems worthy of investigation.Clinical features, molecular features, and response to therapy allow us to identify patients at greater or lesser risk of relapse.32 The adolescent and young adult population seems apt for a trial of such a strategy. Favorable cytogenetics are uncommon, and the marrow relapse rate is substantial.33 The burden of current therapy is already extreme and the efficacy of conventional salvage therapy poor.12Estimating a 20% relapse rate between 10 months and 36 months and q3month sampling, 8/10 patients would have 72 negative assays, and two relapsing patients might have 9 assays, for a total of 81 assays with about 1/40 being positive.Serial PB sampling adds little to the burden of treatment. Detection of confirmed treatment failure at an MRD level, allows immediate use of blinatumomab or CAR T-cells with a high probability to proceed to transplant MRD negative. Another round of toxic cytotoxic chemotherapy, much like the therapy that already failed, might be avoided. “If not now, when.”References1. Rheingold SR, Bhojwani D, Ji L, et al. Determinants of survival after first relapse of acute lymphoblastic leukemia: a Children’s Oncology Group study. Leukemia. 2024.2. Rheingold SR, Ji L, Xu X, et al. Prognostic factors for survival after relapsed acute lymphoblastic leukemia (ALL): A Children’s Oncology Group (COG) study. In: American Society of Clinical Oncology; 2019.3. Freyer DR, Devidas M, La M, et al. Postrelapse survival in childhood acute lymphoblastic leukemia is independent of initial treatment intensity: a report from the Children’s Oncology Group. Blood. 2011;117(11):3010-3015.4. Hasan H, Goddard K, Howard AF. Utility of the number needed to treat in paediatric haematological cancer randomised controlled treatment trials: a systematic review. BMJ open. 2019;9(2):e022839.5. van Binsbergen AL, de Haas V, van der Velden VHJ, de Groot-Kruseman HA, Fiocco MF, Pieters R. Efficacy and toxicity of high-risk therapy of the Dutch Childhood Oncology Group in childhood acute lymphoblastic leukemia. Pediatric blood & cancer. 2022;69(2):e29387.6. Gupta A, Damania RC, Talati R, O’Riordan MA, Matloub YH, Ahuja SP. Increased Toxicity Among Adolescents and Young Adults Compared with Children Hospitalized with Acute Lymphoblastic Leukemia at Children’s Hospitals in the United States. Journal of adolescent and young adult oncology. 2021;10(6):645-653.7. Chang TC, Chen W, Qu C, et al. Genomic Determinants of Outcome in Acute Lymphoblastic Leukemia. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2024:Jco2302238.8. Pieters R, Mullighan CG, Hunger SP. Advancing Diagnostics and Therapy to Reach Universal Cure in Childhood ALL. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2023;41(36):5579-5591.9. Kleppe M, Levine RL. Tumor heterogeneity confounds and illuminates: assessing the implications. Nature medicine. 2014;20(4):342-344.10. Dhillon S. Inotuzumab Ozogamicin: First Pediatric Approval.Paediatric drugs. 2024;26(4):459-467.11. O’Brien MM, Ji L, Shah NN, et al. Phase II Trial of Inotuzumab Ozogamicin in Children and Adolescents With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia: Children’s Oncology Group Protocol AALL1621. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2022;40(9):956-967.12. Brown PA, Ji L, Xu X, et al. Effect of Postreinduction Therapy Consolidation With Blinatumomab vs Chemotherapy on Disease-Free Survival in Children, Adolescents, and Young Adults With First Relapse of B-Cell Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. Jama. 2021;325(9):833-842.13. Hogan LE, Brown PA, Ji L, et al. Children’s Oncology Group AALL1331: Phase III Trial of Blinatumomab in Children, Adolescents, and Young Adults With Low-Risk B-Cell ALL in First Relapse. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2023;41(25):4118-4129.14. Lamble AJ, Myers RM, Taraseviciute A, et al. Preinfusion factors impacting relapse immunophenotype following CD19 CAR T cells.Blood advances. 2023;7(4):575-585.15. Park JH, Rivière I, Gonen M, et al. Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia. The New England journal of medicine. 2018;378(5):449-459.16. Gökbuget N, Dombret H, Bonifacio M, et al. Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia. Blood. 2018;131(14):1522-1531.17. Queudeville M, Stein AS, Locatelli F, et al. Low leukemia burden improves blinatumomab efficacy in patients with relapsed/refractory B-cell acute lymphoblastic leukemia. Cancer. 2023;129(9):1384-1393.18. Jen EY, Xu Q, Schetter A, et al. FDA Approval: Blinatumomab for Patients with B-cell Precursor Acute Lymphoblastic Leukemia in Morphologic Remission with Minimal Residual Disease. Clinical cancer research : an official journal of the American Association for Cancer Research. 2019;25(2):473-477.19. Mastrangelo R, Poplack D, Bleyer A, Riccardi R, Sather H, D’Angio G. Report and recommendations of the Rome workshop concerning poor-prognosis acute lymphoblastic leukemia in children: biologic bases for staging, stratification, and treatment. Medical and pediatric oncology. 1986;14(3):191-194.20. Rogers PC, Bleyer WA, Coccia P, et al. Yield of unpredicted bone-marrow relapse diagnosed by routine marrow aspiration in children with acute lymphoblastic leukaemia. A report from the Children’s Cancer Study Group. Lancet (London, England). 1984;1(8390):1320-1322.21. Rubnitz JE, Hijiya N, Zhou Y, Hancock ML, Rivera GK, Pui CH. Lack of benefit of early detection of relapse after completion of therapy for acute lymphoblastic leukemia. Pediatric blood & cancer. 2005;44(2):138-141.22. Contreras Yametti GP, Ostrow TH, Jasinski S, Raetz EA, Carroll WL, Evensen NA. Minimal Residual Disease in Acute Lymphoblastic Leukemia: Current Practice and Future Directions. Cancers. 2021;13(8).23. Svaton M, Skotnicova A, Reznickova L, et al. NGS better discriminates true MRD positivity for the risk stratification of childhood ALL treated on an MRD-based protocol. Blood. 2023;141(5):529-533.24. Buchmann S, Schrappe M, Baruchel A, et al. Remission, treatment failure, and relapse in pediatric ALL: an international consensus of the Ponte-di-Legno Consortium. Blood. 2022;139(12):1785-1793.25. Raff T, Gökbuget N, Lüschen S, et al. Molecular relapse in adult standard-risk ALL patients detected by prospective MRD monitoring during and after maintenance treatment: data from the GMALL 06/99 and 07/03 trials. Blood. 2007;109(3):910-915.26. Paganin M, Fabbri G, Conter V, et al. Postinduction minimal residual disease monitoring by polymerase chain reaction in children with acute lymphoblastic leukemia. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2014;32(31):3553-3558.27. Cheng S, Inghirami G, Cheng S, Tam W. Simple deep sequencing-based post-remission MRD surveillance predicts clinical relapse in B-ALL.Journal of hematology & oncology. 2018;11(1):105.28. Wang Y, Xue YJ, Jia YP, Zuo YX, Lu AD, Zhang LP. Re-Emergence of Minimal Residual Disease Detected by Flow Cytometry Predicts an Adverse Outcome in Pediatric Acute Lymphoblastic Leukemia. Frontiers in oncology. 2020;10:596677.29. Gökbuget N, Boissel N, Chiaretti S, et al. Management of ALL in adults: 2024 ELN recommendations from a European expert panel.Blood. 2024;143(19):1903-1930.30. Network NCC. Acute Lymphoblastic Leukemia (Version 2.2024) 2024.31. Pierce E, Mautner B, Mort J, et al. MRD in ALL: Optimization and Innovations. Current hematologic malignancy reports. 2022;17(4):69-81.32. Hunger SP, Loh ML, Whitlock JA, et al. Children’s Oncology Group’s 2013 blueprint for research: acute lymphoblastic leukemia.Pediatric blood & cancer. 2013;60(6):957-963.33. Burke MJ, Devidas M, Chen Z, et al. Outcomes in adolescent and young adult patients (16 to 30 years) compared to younger patients treated for high-risk B-lymphoblastic leukemia: report from Children’s Oncology Group Study AALL0232. Leukemia. 2022;36(3):648-655.

Background: Sinusoidal obstruction syndrome (SOS), a serious complication after hematopoietic cell transplant (HCT), is associated with multi-organ dysfunction (MOD) and a high mortality rate. In severe cases, continuous kidney replacement therapy (CKRT) is initiated to manage fluid overload (FO) and acute kidney injury. Studies that evaluate the use of CKRT in this population are lacking. The aim of our study was to assess the outcome of critically ill children with severe SOS post HCT who received CKRT. We also sought to assess factors associated with survival and liberation post CKRT. Procedure: Retrospective review of all children admitted to the intensive care unit (ICU) with SOS post HCT who received CKRT from January 2010 to August 2022. Results: Among the 53 children who received CKRT post HCT, 13 had severe SOS. The median age was 6 years; 62% were males, and most (77%) received allogeneic HCT. In this cohort, 92% required respiratory support and 85% required vasopressor support. The ICU survival rate was 62%. Survivors experienced lower cumulative FO on the 2 days following CKRT initiation (-4.2% in survivors versus -0.5% in non-survivors, p=0.07). Higher urine output on D1 and D2 after discontinuation of CKRT was associated with successful liberation. Conclusions: In this study of post-HCT children with SOS and MOD who received CKRT, 62% survived until ICU discharge. This survival rate is encouraging as it approximates the survival rates of general pediatric cohorts treated with CKRT. Reducing FO after initiation of CKRT can improve survival in these children.

Background: Autosomal recessive severe congenital neutropenia (SCN) has been associated with homozygous variants in the HAX1(HCLS1 Associated Protein X-1) gene. In this rare disease, ovarian insufficiency has been reported only in nine female patients in the literature. There is insufficient data on the gonadal function of patients with SCN due to HAX1 gene variant ( HAX1-SCN ) in childhood and the age of onset of premature ovarian insufficiency (POI) is unknown. The aim of this cross-sectional study was to evaluate the gonadal functions and pubertal development in pediatric patients with HAX1-SCN. Methods: Forty-five patients, including 24 females (median age 11.3 years, 1.5–31 years, 13 pubertal and 11 prepubertal), and 21 males (median age 9.5 years, 3–18.8 years, 7 pubertal and 14 prepubertal), followed in 7 centers, were included. POI is defined as a menstrual disturbance with increased follicle stimulating hormone (FSH) and low anti-Mullerian hormone (AMH). We classified prepubertal female patients as impending POI when they had low AMH and high FSH values, indicating impaired ovarian function. Results: A homozygous single nucleotide insertion (position 130-131insA) leading to a premature stop codon; p.Trp44*(c.132G>A) variant in HAX1 gene was detected in 42 (93.3%) affected individuals. Other homozygous variants were p.Arg86*(c.256C>T) and p.Glu60Aspfs*25(c.180delA). We detected elevated serum FSH levels in 10/11 (90.9%) of prepubertal female patients, supporting the diagnosis of impending POI, and in 12/13 (92.3%) of pubertal female patients, classifying them as POI. All female patients had low AMH levels. Male patients did not exhibit gonadal insufficiency. Conclusions: This is the first and largest case series covering early childhood to evaluate patients with HAX1-SCN for gonadal functions. It has been observed that pubertal girls develop POI, prepubertal girls are at increased risk for gonadal failure and male patients are not affected. Our results suggest that HAX1 has an important role in ovarian maturation and/or function. The genotype-phenotype relationship of these patients and the effect of clinical features of SCN on gonadal function should be further investigated.

Background: Paediatric palliative care (PPC) is considered an essential component of the management of children and adolescents with cancer. The International Society of Paediatric Oncology Global Mapping Programme surveyed hospital-based paediatric oncology facilities across Africa from 2018-2020 to document PPC and provision of PPC services. Procedure: An electronic and paper survey were widely distributed to elicit the presence of components of PPC: PPC teams, bereavement counselling services, patient support groups, and spiritual and religious support. Results were correlated with the countries’ Gini coefficient, World Bank income status indicators and Human Development Index. Results: Hospital-based paediatric oncology facilities in 16/54 African countries reported having all four PPC services while those in 11 countries reported having none of the four PPC services. No clear correlations were found between provision of such services and selected economic factors. Conclusions: This study demonstrates that hospital-based paediatric oncology facilities with limited resources caring for children and adolescents can provide PPC. Adoption of the World Health Organisation’s conceptual framework for palliative care and knowledge transfer between African facilities on the integration of PPC into paediatric oncology care, would benefit the increasing numbers of children and adolescents with cancer across the continent.

Impact of Duffy-Associated Neutrophil Count on Maintenance Chemotherapy Management in a Child with Acute Lymphoblastic LeukemiaDerek K. Zachman1,2, Jonathan G. Bardahl1, Laurie A. Graves1, and Lars M. Wagner11Division of Pediatric Hematology-Oncology, Duke University Medical Center, Durham NC2Corresponding author:2301 Erwin Road, Durham NC 27710Phone: 919-684-3401, Fax: 919-668-4447dkz3@duke.eduWord Counts: 828Number of Figures/Tables/Supporting Documents: 1 FigureRunning Title: Duffy Associated Neutrophil Count in Pediatric LeukemiaKeywords: pediatric oncology, acute lymphoblastic leukemia, Duffy-associated neutrophil countAbbreviations:

IntroductionTAM is characterized by a transient proliferation of abnormal myeloid cells in the bone marrow, leading to an excess of immature cells circulating in the peripheral blood [2]. TAM diagnosis is associated with the presence of GATA1 mutations, but other features such as blasts on peripheral blood smear, flow cytometry immunophenotype or cytogenetics can be indicative of TAM. This patient’s case is unusual due to the GATA1 mutation-negative status. The GATA1 gene encodes a transcription factor crucial for normal hematopoiesis and mutations in this gene are associated with myeloid disorders including TAM [3]. TAM leads to a wide range of hematologic abnormalities and clinical complications including hyperviscosity syndrome with potential for thrombosis, hydrops fetalis, pericardial effusion, respiratory distress, hypereosinophilia, pseudohyperkalemia, hyperbilirubinemia with liver failure, multi-organ failure and potential for death [1,2,5,14]. Patients with TAM require timely diagnosis as well as close follow up, as 20-30% of these patients subsequently develop myeloid leukemia associated with Down Syndrome (ML-DS) before the age of four [4]. GATA1 mutations have, to date, been discovered in nearly all patients with TAM and ML–DS [7]. The absence of aGATA1 mutation in this case raises the question of an alternative molecular mechanism contributing to the development of TAM and extreme thrombocytosis in this patient.