Background Adolescent and young adult (AYA) women with sickle cell disease (SCD) have increased pregnancy-related health risks and are prescribed potentially teratogenic medications, yet little is known about pediatric SCD provider contraceptive practices. We aimed to assess pediatric hematology providers’ beliefs, practices, motivators, and barriers for providing contraceptive care to female AYA with SCD. Methods Guided by the Health Belief Model (HBM), we developed a 25-question, web-based survey to assess providers’ practices. Survey links were distributed nation-wide to pediatric SCD and/or general hematology providers through their publicly available emails and by request to directors of U.S. accredited Pediatric Hematology-Oncology fellowship programs for distribution to their SCD providers. Data analysis included descriptive statistics, chi-square analysis, logistic regression. Results Of 177 respondents, 160 surveys meeting inclusion criteria were analyzed. Most providers reported counseling (77.5%) and referring female AYA patients for contraception (90.8%), but fewer reported prescribing contraception (41.8%). Counseling practices significantly differed in trainees versus established providers (54% vs. 85%, p<0.001) with a similar trend for prescribing (p=0.05). Prescription practices did not differ significantly by provider beliefs regarding potential teratogenicity of hydroxyurea. Key motivators included patient request and disclosure of sexual activity. Key barriers included inadequate provider training, limited visit time, and perceived patient/parent interest. Conclusion Provider contraceptive practices for female AYA with SCD varied, especially by provider status. Health beliefs regarding teratogenic potential of hydroxyurea did not correlate with contraceptive practices. Clinical guidelines, provider training, and patient/parent decision-making tools may be tested to assess whether provider contraceptive practices could be improved.

Background: Sickle cell disease (SCD) is characterized by both acute and chronic complications that affect the daily lives of patients and lower their quality of life. Objective: To describe the health-related quality of life (HRQoL) and the associated factors in children aged 8 to 17 with SCD attending the paediatric haematology clinic at Kamuzu Central Hospital (KCH) in Lilongwe, Malawi. Methods: A mixed methods cross sectional study was conducted at KCH. Patient data was collected with the aid of a standardized case report form. HRQoL was assessed using PedsQL™ Sickle Cell Disease Module by child’s report. Associations between HRQoL scores and independent variables were evaluated by a linear regression model. In-depth interviews were then carried out and the qualitative data was analyzed using content thematic analysis. Results: A hundred and sixty-three children with SCD were enrolled, 52.1% were females. Their median age was 11.2±2.7 years. The mean global HRQoL score of the children was 62±17.3. The highest scores were in the treatment domain (72.5±15.1) while the lowest scores were in the emotions domain (55.2±28.7). The mean pain score was 58.8±16.3. The factors associated with low HRQoL scores were pain (β-coefficient -6.97 CI (-3.07,-15.58); p value 0.034) and low haemoglobin levels (β-coefficient 2.29 CI (0.65-3.91); p value 0.006 ). Conclusion: The HRQoL of this population is low. Pain and low hemoglobin were significantly associated with low HRQoL scores. A biopsychosocial model of heath care delivery and health campaigns are recommended to improve the HRQoL of the children.

Monolobated Megakaryocytes in Diamond Blackfan Anemia withRPL5 Mutation at Disease Presentation Mimicking Myelodysplastic Syndrome

Type of manuscript : CorrespondenceTitle : Stomatocytes - a whistleblower for future familial cardiovascular events- unraveling the diagnosis of Sitosterolemia in an Indian family. Running title : Hemolytic manifestation of sitosterolemia in an Indian familyAuthors : Richa Chauhan¹, Manas Kalra², Surbhi Singh ¹*, Anupam Sachdev², Jyoti Kotwal¹Affiliation : Departments of Hematology¹ and Pediatric hemato-oncology2, Sir Gangaram Hospital, New DelhiAuthor’s contribution: The manuscript is original and all authors have contributed equally to manuscript preparation.Text word count : 1091Number of Figures : 01Keywords : macrothrombocytopenia, stomatocytosis, sitosterolsDisclosure statement : NoneFunding : NilConflicts of interest : There is no conflicts of interest.

OBJECTIVES In the etiology of childhood cancers, many genetic and environmental factors play a role. One of these factors is cigarette smoking and the main source of tobacco smoke exposure of children is parental smoking. However, establishing a causal relationship between parental smoking and childhood cancers has proven challenging due to difficulties in accurately detecting tobacco smoke exposure METHODS To address this issue, we used hair cotinine analysis and a questionnaire to get information about tobacco smoke exposures of pediatric cancer patients and healthy children. 104 pediatric cancer patients and 99 healthy children participated in our study. Parental smoking behaviours (pre-conceptional, during pregnancy and current smoking) and environmental tobacco smoke (ETS) exposures of children are compared. RESULTS We have found no differences between two groups by means of maternal smoking behaviours. However, the rates of paternal pre-conceptional smoking and smoking during pregnancy were significantly low in cancer patients (p<0,05). These data suggests that social desirability bias among fathers of cancer patients may have contributed to this discrepancy. According to questionnaire cancer patients had significantly lower ETS exposures than healthy children (p<0,05). However, ETS exposure assessment through cotinine analysis demonstrated that cancer patients had higher exposure to ETS compared to healthy children (p<0.001). CONCLUSION Our findings provide evidence supporting the potential role of smoking as a risk factor for childhood cancers. This study also revealed that questionnaires could cause biases. We suggest that cotinine analysis along with validated questionnaires can be used to prevent biases in studies of tobacco smoke in the etiology of childhood cancers.

In March 2023, over 800 researchers, clinicians, patients, survivors, and advocates from the pediatric oncology community met to discuss the progress, plans, and future priorities of the National Cancer Institute’s Childhood Cancer Data Initiative. We present here the status of the initiative’s efforts in building its data ecosystem to provide access to childhood cancer data; updates on the Molecular Characterization Initiative; plans for implementing a Coordinated National Initiative for Rare Cancers in Children and Young Adults; and efforts to establish a framework for computable consent.

Children’s Oncology Group’s 2023 Blueprint For ResearchDouglas S. Hawkins,1 Lia Gore2Department of Pediatrics, Seattle Children’s Hospital, University of Washington, Seattle, WADepartment of Pediatrics, University of Colorado School of Medicine and Center for Cancer and Blood Disorders, Children’s Hospital Colorado,, Aurora, CO

Background: Clinical informatics tools to integrate data from multiple sources have the potential to catalyze population health management of childhood cancer survivors at high risk for late heart failure through the implementation of previously validated risk calculators. Methods: The Oklahoma cohort (n=365) harnessed data elements from Passport for Care (PFC) and the Duke cohort (n=274) integrated cancer registry and electronic health record data, using standard query language, to automatically extract chemotherapy exposures for survivors <18 years old at diagnosis. The Childhood Cancer Survivor Study (CCSS) late cardiovascular risk calculator was implemented and risk groups for heart failure were compared to the Children’s Oncology Group (COG) Long-Term Follow-up Guidelines. Results: The Oklahoma and Duke cohorts both observed good overall concordance between the CCSS and COG risk groups for late heart failure with weighted Kappa statistics of 0.70 and 0.75, respectively. Low-risk groups showed excellent concordance (Kappa >0.9). Moderate and high-risk groups showed moderate concordance (Kappa 0.44-0.60 across both cohorts). In the Oklahoma cohort, adolescents at diagnosis were significantly less likely to receive guideline-adherent care for echocardiogram surveillance compared with survivors <13 years old at diagnosis (OR 0.22; 95% CI 0.10-0.49). Conclusions: Clinical informatics tools represent a feasible approach to leverage discrete data elements regarding key treatment exposures from PFC or the EHR to successfully implement previously validated late cardiovascular risk prediction models on a population health level. Real-world evidence on the concordance of CCSS, COG, and IGHG risk groups promises to refine current guidelines and identify inequities in guideline-adherent care.

Title: Vaccine Preventable Illness After Blinatumomab Therapy: A Case ReportAuthors: Katie Voelz MD1,2, Anthony Salvatore DO1, Sudarshawn Damodharan DO1,2 & Cathy Lee-Miller MD1,21Department of Pediatrics, University of Wisconsin School of Medicine & Public Health, Madison, WI, USA2Division of Pediatric Hematology, Oncology and Bone Marrow Transplant, University of Wisconsin School of Medicine & Public Health, Madison, WI, USACorrespondence:Cathy Lee-MillerUniversity of Wisconsin School of Medicine & Public Health1111 Highland Ave, WIMR 4105Madison, WI 53705Email: calee4@wisc.eduWord Count: Main Text: 848Manuscript contains 1 TableShort running Title: Vaccine-preventable, ALL, immunotherapyKeywords: Blinatumomab, ALL, vaccination, pediatrics

Atypical hemolytic uremic syndrome (aHUS) is an infrequently encountered complement-mediated thrombotic microangiopathy (TMA) usually associated with germline variants in genes of the complement system. Clinical findings of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI) with severe hypertension arise due to aberrant complement protein activation in the circulation and significant endothelial damage. Transplant-associated thrombotic microangiopathy has been increasingly recognized after high dose carboplatin, etoposide, and melphalan-chemotherapy followed by autologous hematopoietic stem cell rescue for treatment of children with neuroblastoma (NB). We report the case of a 13-month-old boy with metastatic neuroblastoma who developed aHUS during the first cycle of induction chemotherapy. Germline testing revealed a Complement factor H (CFH) gene mutation, Cys357Arg, which is currently classified as a variant of uncertain significance (VUS), although likely pathogenic based on molecular modeling as well as this patient’s clinical presentation. The patient has been successfully managed with complement blockade therapy with no recurrence of disease. We review presentations of neuroblastoma with hypertension, along with AKI and thrombocytopenia, to raise awareness about the potential for aHUS in patients with newly diagnosed NB.

Prolonged Remission in Multiple Relapsed MLL-rearranged Infant B-ALL with Inotuzumab OzogamicinAkhila Lattupally MD1, Adonis Lorenzana MD1, Gregory Anthony Yanik MD2, Danielle Bell MD1,31. Ascension St. John Children’s Hospital, Detroit, Michigan, United States.2. C.S. Mott Children’s Hospital – University of Michigan, Ann Arbor, Michigan, United States.3. Children’s Hospital of Michigan, Detroit, Michigan, United States.Corresponding Author: Akhila Lattupally MDAddress: 22101 Moross Rd, PB2, Suite 70, Detroit, Michigan 48236Phone: 469-468-7978Fax: 313-343-4756Email:Akhila.Lattupally@ascension.orgWord Count: Main text: 841 wordsNumber of Tables: 0 Number of Figures: 0 Number of Supporting Information Files: 0Running Title: Remission in Infant ALL with Inotuzumab Ozogamicin.Keywords: Infant Leukemia, ALL Relapse, Immunotherapy

Background : Combining immune checkpoint inhibitors (ICI) with chemotherapy may improve treatment response in children with solid tumors. We sought to determine the feasibility of combining v incristine, i rinotecan, and t emozolomide with the ICI a tezolizumab in children with relapsed or refractory s olid tumors (VITAS). Methods: Patients ≥ 6 months and ≤ 18 years old with a relapsed or refractory solid tumor, no prior ICI, and evaluable disease per RECIST v1.1 were eligible for the Phase I cohort (NCT04796012). Patients received atezolizumab 15 mg/kg on day 1, vincristine 1.5 mg/m 2 on day 1, irinotecan 50 mg/m 2 on days 1-5, and temozolomide 100 mg/m 2 on days 1-5 in 21-day cycles. Primary endpoint was the number of patients with dose-limiting toxicities (DLT) in the first two cycles of therapy. Results : Six patients (median age: 14 years) with rhabdomyosarcoma (n=3), osteosarcoma (n=2), and Ewing sarcoma (n=1) received therapy and were evaluable for toxicity. Patients received a median of 7 (range: 2 to 20) cycles of treatment. No patients experienced a DLT. One patient experienced Grade 2 immune-related colitis. Four patients experienced Grade ≥ 3 adverse events (decreased neutrophil count, febrile neutropenia, weight loss, anorexia). One patient with rhabdomyosarcoma had a sustained partial response through 16 cycles. One patient with relapsed pulmonary osteosarcoma has ongoing stable disease through 20 cycles. Conclusions : Atezolizumab combined with vincristine, irinotecan, and temozolomide was feasible and well tolerated in children with solid tumors. Efficacy of this regimen is now being assessed in relapsed and refractory rhabdomyosarcoma in an ongoing Phase II cohort.

Background: While intravenous fluid (IVF) therapy in patients with sickle cell disease (SCD) admitted for a vaso-occlusive episodes (VOE) can help reduce red blood cell sickling, clinical practice varies across institutions. We examined the relationship between IVF therapy and hospital length of stay (HLOS), as well as adverse events, such as acute chest syndrome (ACS), pediatric intensive care unit (PICU) transfer and 28-day readmission. Methods: This is a single-center retrospective analysis of SCD VOE hospitalizations between January 2015 and April 2020. Patients with SCD, age 0-30, with consecutive hospitalizations for VOE were included. For the first 3 days of each admission, an “IVF ratio” was calculated by dividing actual IVF rate administered by weight-based maintenance IVF (mIVF) rate. Results: A total of 617 hospitalizations for 161 patients were included. Mean HLOS was 5.7 days, (SD 3.9), and mean IVF volume over the first 3 days of admission was 139.6 ml/kg/day (SD 57.8). Multivariate analysis showed that for each additional 0.5 times the mIVF rate, HLOS increased by 0.53 days (P<0.001; 95% CI: 0.609–0.989), but there was no significant association between IVF therapy and adverse events. History of chronic pain was associated with increased odds of readmission (OR, 6.4; 95% CI: 3.93 – 10.52). Conclusions: Despite the theoretical potential for IVF therapy to slow down the sickling process, our findings suggest that increased IVF therapy was associated with prolonged HLOS, which places a burden on patients, families, and the health system.

Title Successful treatment with haploidentical PBSCT with post-transplant cyclophosphamide in a child with relapsed neuroblastoma after autologous PBSCT

A document by Thangaraj Abiramalatha. Click on the document to view its contents.

Precursor B-cell Acute Lymphoblastic Leukemia in a pediatric patient with Bainbridge-Ropers Syndrome

A document by Anees Ahmed. Click on the document to view its contents.

Introduction There is lack of diagnostic and treatment resources with variable access to childhood cancer treatment in low- and middle-income countries (LMIC), which may lead to subsequent poor survival. The primary aim of this study is to determine the prevalence and types of T&CM used in Cameroon. Secondarily, we explored determinants of T&CM use, associated costs, perceived benefits and harm, and disclosure of T&CM use to medical team. Method A prospective, cross-sectional survey amongst parents and carers of children younger than 15 years of age who had a cancer diagnosis and received cancer treatment at three Baptist Mission hospitals between November 2017 and February 2019. Results Eighty participants completed the survey. Median patient age was 8.1 years (IQR4.1 – 11.1). There was significant availability (90%) and use (67.5%) of T&CM, while 24% thought T&CM would be good for cancer treatment. Common T&CM remedies included herbs and other plant remedies or teas taken by mouth, prayer for healing purposes and skin cutting. Living more than 5 hours away from the treatment center (p=0.030), anticipated costs (0.028), and a habit of consulting a traditional healer when sick (p=0.006) were associated with the use of T&CM. T&CM was mostly paid for in cash (36.3%) or provided free of charge (20%). Of importance was the fact that nearly half (44%) did not want to disclose the use of TM to their doctor. Conclusion Pediatric oncology patients used T&CM before and during treatment but would be unlikely to disclose to the child’s health care team.