Title PageTitle : Pancytopenia in a child with cystic fibrosis and severe copper deficiency: Insight from bone marrow evaluationAuthors : Maggie D. Seblani1,2; Susanna A. McColley2,3,4; Shunyou Gong5; Lee M. Bass2,6; Sherif M. Badawy1,2Affiliations : 1 Division of Hematology, Oncology and Stem Cell Transplant, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USA; 2 Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; 3 Division of Pulmonary and Sleep Medicine, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USA; 4 Stanley Manne Children’s Research Institute, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, Illinois, USA; 5 Division of Pediatric Pathology, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL; 6 Division of Gastroenterology, Hepatology and Nutrition, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL.Correspondence: Sherif M. Badawy, MD, MS, MBBCh, 225 E. Chicago Ave., Box #30, Chicago, IL, 60611, office: 312-227-4836, fax: 312-227-9376, e-mail: [email protected] count: 498Number of Tables, Figures, and Supplemental files : 1Running title: Bone marrow findings with severe copper deficiencyKeywords: pancytopenia, anemia, leucopenia, neutropenia, thrombocytopenia, copper deficiency, ring sideroblasts, copper supplement, cystic fibrosis, malabsorptionConflict of Interest: Author has no conflicts of interest to disclose.

Introduction/Objectives: We evaluated the length of time immunocompromised children (ICC) remain positive for SARS-CoV-2, identified factors associated with viral persistence and determined cycle threshold (CT) values of children with viral persistence as a surrogate of viral load. Methods: We conducted a retrospective cohort study of ICC at a pediatric hospital from March 2020-2021. Immunocompromised status was defined as primary, secondary or acquired due to medical comorbidities/immunosuppressive treatment. The primary outcome was time to first-of-two consecutive negative SARS-CoV-2 Polymerase chain reaction (PCR) tests at least 24 hours apart. Testing of sequential clinical specimens from the same subject was conducted using the Centers for Disease Control (CDC) 2019-nCoV Real-Time RT-PCR Diagnostic Panel assay. Descriptive statistics, Kaplan-Meier curve median event times and log-rank-sum tests were used to compare outcomes between groups. Results: Ninety-one children met inclusion criteria. Median age was 15.5 years (IQR 8-18 yrs), 64% were male, 58% were white, and 43% were Hispanic/Latinx. Most (67%) were tested in outpatient settings and 58% were asymptomatic. The median time to two negative tests was 42 days (IQR 25.0,55.0), with no differences in median time by illness presentation or level of immunosuppression. Seven children had >1 sample available for repeat testing, and 5/7 (71%) children had initial CT values of <30, (moderate to high viral load); 4 children had CT values of <30 3-4 weeks later, suggesting persistent moderate to high viral loads. Conclusions: Most ICC with SARS-CoV-2 infection had mild disease, with prolonged viral persistence >6 weeks and moderate to high viral load.

Background Mature aggressive B-cell lymphoma are heterogenous malignancies that make up more than half of all diagnosed Non-Hodgkin lymphoma in children and adolescents. The overall survival rate increased over the last decades to 80–90%, due to fine tuning of polychemotherapy. However, new therapeutic implications are needed to further increase the overall survival. Current clinical trials analyze the therapeutic effect of rituximab in pediatric patients, while the mechanism of action in vivo is still not fully understood. Methods Effector molecules important for tumor defense were analyzed before and at day five after rituximab treatment via flow cytometry. Serum rituximab levels were measured with an ELISA. Results We evaluated patient parameters that may affect treatment response in relation to rituximab administration and serum rituximab levels. We indeed found a reduction of FcγRII levels after rituximab treatment in monocyte subtypes, while FcγRI expression was significantly increased, pointing to exhaustion of FcγRII mediated B cell depletion and compensation via FcγRI mediated trogocytosis. Serum levels of proinflammatory marker proteins S100A8/A9 and S100A12 significantly decreased after treatment to normal levels from an overall proinflammatory state before treatment. CD57, perforin and granzyme B expression decreased after treatment, probably due to exhaustion of NK cells. Conclusion The highlighted effects of rituximab treatment on patient’s immune response help understanding the biology behind tumor defense mechanisms and effector function. After subsequent studies, these novel insights might be translated into patient care and could contribute to improve treatment of pediatric patients with mature aggressive B-cell lymphoma.

Background: Clear cell sarcoma (CCS), epithelioid sarcoma, and synovial sarcoma are rare tumors historically identified as high risk for lymph node metastasis. Nodal metastasis in adults with these subtypes has been described. This study investigates incident nodal metastasis and associated survival in children with these subtypes. Procedure: Using the National Cancer Database (2004-2015), we created a retrospective cohort of 1303 patients (aged ≤25 years) who underwent local control therapy for CCS, epithelioid sarcoma, and synovial sarcoma. Kaplan-Meier curves estimated overall survival (OS) by subtype. Stratifying on subtype, Cox regressions assessed OS by lymph node sampling status and nodal metastasis. Results: There were 103 (7.9%) patients with CCS, 221 (17.0%) with epithelioid sarcoma, and 979 (75.1%) with synovial sarcoma. Lymph node sampling was more frequent in patients with CCS (56.3%) and epithelioid sarcoma (52.5%) versus synovial sarcoma (20.5%, p<0.001). Synovial sarcoma metastasized to lymph nodes less frequently than CCS or epithelioid sarcoma (2.2% vs. 14.6% and 15.0%, p<0.001). Across all subtypes, lymph node metastasis was associated with inferior OS (HR 2.10, CI 1.44-3.07, p<0.001). Lymph node sampling was associated with improved OS in CCS (HR 0.35, CI 0.15-0.78, p=0.010), inferior OS in synovial sarcoma (HR 1.60, CI 1.13- 2.25, p=0.007), and no statistical association with OS in epithelioid sarcoma. Conclusions: Lymph node metastasis is rare in children with synovial sarcoma. Lymph node sampling procedures were not consistently performed for patients with CCS or epithelioid sarcoma, but improved OS supports routine lymph node sampling in children with CCS.

Bone tumors are a group of histologically diverse diseases which occur across all ages. Two of the commonest, osteosarcoma (OS) and Ewing sarcoma (ES), are regarded as characteristic AYA cancers with an incidence peak in AYAs. They are curable for some but associated with unacceptably high rates of treatment failure and morbidity. The introduction of effective new therapeutics for bone sarcomas is slow, and to date, complex biology has been insufficiently characterized to allow more rapid therapeutic exploitation. This review focuses on current standards of care, recent advances that have or may soon change that standard of care and challenges to the expert clinical research community that we suggest must be met.

Background Consultation of specialty palliative care remains uncommon in pediatric stem cell transplant (SCT) despite growing evidence that early integration of palliative care improves outcomes in patients with advanced cancers or undergoing SCT. Little is known about how multidisciplinary pediatric SCT teams perceive palliative care and its role in SCT. Procedure We conducted semi-structured interviews of members of a multi-disciplinary SCT team to understand their perceptions of palliative care, how specialty palliative care is integrated into SCT, and to identify barriers to increased integration. Eligible participants included physicians, nurses, nurse practitioners, social workers, and child life specialists. Data was analyzed using thematic analysis. Results Four major themes were identified. First, SCT team members held a favorable perception of the palliative care team. Second, participants desired increased palliative care integration in SCT. Third, participants believed that the palliative care team had insufficient resources to care for the large number of SCT patients which led to the SCT team limiting palliative care consultation. And, finally, the lack of a standardized palliative care consultation process prevented greater integration of palliative care in SCT. Conclusions SCT team members held a favorable perception of palliative care and saw a role for greater palliative care integration throughout the SCT course. We identified modifiable barriers to greater palliative care integration. SCT teams who desire greater palliative care integration may adapt and implement an existing model of palliative care integration in order to improve standardization and increase integration of specialty palliative care in SCT.

A retrospective analysis of recurrent pediatric ependymoma reveals extremely poor survival ind ineffectiveness of current treatments across central nervous locations and molecular subgroups. Tryggve Lundar MD, PhD1,2, Bernt Johan Due-Tønnessen MD,PhD1Radec Fric MD,PhD1Department of Neurosurgery, Oslo University Hospital1and University of Oslo2Correponding author:Tryggve LundarDepartment of NeurosurgeryOslo University HospitalPostboks 4950 Nydalen, Oslo, NorwayEmail: [email protected] word count: 474Short running title: GTR can improve outcome after relapse of pediatric ependymomaKey words: Pediatric ependymoma, relapse, repeat surgical resection (GTR)Number of tables: 0Number of figures: 0Letter to the EditorPediatr Blood CancerDear Editor,RE: Ritzmann TA, Rogers HA, Paine SML, Storer LCD, Jacques TS, Chapman RJ, Ellison D, Donson AM, Foreman NK, Grundy RG.A retrospective analysis of recurrent pediatric ependymoma reveals extremely poor survival ind ineffectiveness of current treatments across central nervous locations and molecular subgroups.Pediatr Blood Cancer 2020;67:e28426https://doi.org/10.1002/pbc.28426Congratulations to the authors with their detailed analysis of further management and outcome in pediatric patients who experience recurrence within a few years after initial treatment for ependymomas.Initial treatment for posterior fossa ependymomas (PFE) is maximal surgical resection (Gross total resection-GTR; if possible) followed by local radiotherapy or chemotherapy in small children. For supratentorial ependymomas (STE) GTR is also recommended (if possible) with or without postoperative radiotherapy.The management at relapses is, however, without consensus. The authors confirm the grave prognosis for these children. In the beginning of the discussion they state: Although primary surgery and irradiation reduced relapse risk variability in different intracranial locations, once a patient recurred these interventions gave, at best, short-term benefits, confirming the need for better therapies.This of course true – better therapies are urgently needed. They point to the lack of consensus regarding treatment at relapse, but recent guidelines have recommended the use of reirradiation and further surgery. In the conclusion they underline that recurrent pediatric ependymoma is highly aggressive with extremely poor outcome.This negative statement, is to some extent, in conflict with the results given under 3.5.2. At relapse: GTR at first relapse was associated with sustained improved EFS (25% vs 0% 10-year survival).This statement is in accord with Vinchon et al1 : Total resection is the only curative treatment for RIE (recurrent intracranial ependymoma) and is often possible, especially when the initial resection was total.How often GTR is within reach at local relapes may be a difficult matter. We have, however, observed several patients who underwent GTR after recurrence, and are tumor-free today after many years of further follow-up(up to 27 years) without any additional treatment2. We recognize that these patients are few compared to the majority of pediatric ependymoma patients who do not grow-up to be well functioning adults. It is, however, important for these small patients and their caretakers to have a hope for cure even after relapse. The role of GTR if possible may be under-communicated.Kind regardsTryggve LundarBernt Johan Due-TønnessenRadek Fric

Background: Postoperative hypocalcemia is a frequent complication after thyroid surgery. Hypoparathyroidism may develop as transient (TtHP), with normalization within six months from surgery, or permanent (PtHP) if the patient requires replacement therapy. The present study analyzes rates and factors associated with the development of TtHP or PtHP following thyroid surgery in a pediatric population. Procedure: A retrospective multicenter study analyzing 363 patients was carried out. We recorded gender, age, tumor size, type of surgery, lymph node dissection, histology. Calcium levels were acquired daily for 72 hours after discharge. Subsequent sample collection was customized on the patient’s hypocalcemia severity. Results: We analyzed 363 patients aged ≤18 years (mean age 14.2 years) who underwent thyroid surgery clustered into age groups (≤15 or >15). Patients mean follow-up was 5.8 years (1-11yrs). At histology 310 (85%) were papillary carcinoma, 32 (9%) were follicular carcinoma, 6 (2%) presented diffuse sclerosing variant of papillary thyroid carcinoma whilst 15 (4%) had familial medullary carcinoma. TtHP developed in 36 (9,9%), PtHP in 20 (5.5%) cases. TtHP was more frequent in younger patients (p=0,009). Both PtHP and TtHP were increased in case of larger tumors (≥2 cm) (p=0,001). All TtHP and PtHP were in TT group. PtHP rate was increased if lymph node dissection was carried out (p<0.001). Conclusions: The risk of hypoparathyroidism is related to younger age, tumor size, TT and lymph node dissection therefore surgeons should tailor surgery as much as possible to avert such complication.

Cobalamin deficiency during treatment of pediatric precursor B-cell lymphoblastic leukemiaHiromi Kinoshita1), Atsuko Watanabe2), Yoshitada Taji1), Moe Yoshimura2), Atsuhiko Ota2), Takashi Fukushima2), Ryuhei Tanaka2), Yasuhiro Ebihara1, 3)1) Clinical Laboratory, 2)Department of Pediatric Hematology/Oncology, 3)Department of Laboratory Medicine, Saitama Medical University International Medical Center, Saitama, JapanCorresponding author: Yasuhiro Ebihara, MD, Department of Laboratory Medicine, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka-shi, Saitama 350-1298, JapanTEL: +81-42-984-4384; FAX: +81-42-984-4384E-mail:[email protected] countMain text: 500Figure: 1Supplementary Table: 1Running title: Cobalamin deficiency in pediatric BCP-ALLKeywords: cobalamin deficiency, pediatric B-cell precursor acute lymphoblastic leukemia, erythroid dysplasia, nutritionTo the editor,There has been considerable progress in supportive therapy and care strategies for patients with cancer, but nutritional problems may still arise during treatment 1. Herein, we report on a 4-year-old boy who was diagnosed with B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Complete remission was achieved and maintained. Eight months later, he underwent late intensification treatment, which contained three cycles of methotrexate 500 mg/m2. BM examination scheduled before he went into the maintenance phase showed erythroid dominance and apparent dysplasia, including megaloblastic change, multinuclearity, karyorrhexis, and nuclear budding, and a few Howell-Jolly bodies were noted in the cytoplasm of some erythroid cells (Figure 1). Myelodysplastic syndrome (MDS) was suspected because he had received several anti-leukemic drugs that could induce treatment-related MDS. These morphological changes are seen in folate and/or cobalamin deficiency, which might be mistaken for MDS or acute leukemia 2, 3. The laboratory investigations (Table S1) revealed a decreased serum cobalamin level of 145 pg/mL, indicating that the erythroid dysplasia was due to cobalamin deficiency. Oral replacement therapy of mecobalamin, 500 µg/day, was started. Ten days later, BM examination revealed that the erythroid dysplasia had mostly disappeared. The final diagnosis was erythroid dysplasia caused by cobalamin deficiency. The patient subsequently underwent maintenance treatment and has remained in CR.A characteristic feature of cobalamin deficiency is nuclear-cytoplasm asynchrony in erythroid maturation, whereby maturation of the nucleus is delayed relative to that of the cytoplasm because cobalamin is essential for DNA synthesis 4, 5. Cobalamin deficiency is very rare in childhood, and is seen mainly in children with inadequate intake, breast-feeding infants with a cobalamin-deficient mother, and those with congenital malabsorption4, 5. The occurrence of cobalamin deficiency in the middle of the ALL treatment is extremely rare for the pediatric patients who can take orally and developing normally. In pediatric ALL patients, the existence of cobalamin deficiency before treatment was reported 6,7, but there is almost no report about cobalamin deficiency during treatment. We could not find any factors which might induce cobalamin deficiency. However, it was possible that the repeated episodes of BM suppression, the recovery from which required more cobalamin for maturation of blood cells, and accumulation of anorexic episodes a caused by administration of anti-leukemic drugs and treatment complications might have led to a gradual decrease in his serum cobalamin level, culminating in cobalamin deficiency. Cobalamin deficiency requires parenteral or oral replacement therapy 4, 8. It is reported that response to replacement is rapid (within 5 days) and megaloblastic anemia can be corrected in 6-8 weeks 4,5. However, the erythroid dysplasia in BM resolved almost completely after 10 days of cobalamin replacement, and improvement in both peripheral blood (Table S1) and BM were clearly achieved in our patient. Although there have been reports of improved laboratory data in peripheral blood 2,4, 5, there are few descriptions on findings in BM 9. Although there has been considerable progress in supportive therapy and care strategies for children with cancer, their nutritional status should be monitored carefully during treatment.

SUCCESSFUL USE OF CRUSHED FORMULATION OF DABRAFENIB AND TRAMETINIB IN A PEDIATRIC GLIONEURAL TUMORTania Mamdouhi1, Anshul Vagrecha2, Alan A. Johnson1,3, Carolyn Fein Levy1,2, Mark Atlas 1,2, Julie I. Krystal 1,2 1 Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY2 Department of Pediatrics, Division of Hematology/Oncology and Cellular Therapy, Cohen Children’s Medical Center, New Hyde Park, NY3 Department of Radiology, Division of Neuroradiology, Long Island Jewish Medical Center, New Hyde Park, NYCorresponding Author : Julie Krystal. Cohen Children’s Medical Center, 269- 01 76th Avenue, Suite 255, New Hyde Park, NY 11040. [email protected]. Phone 718-470-3460. Fax 718-343-4642.Tables: 0Figures: 1Supporting Information Files : 0Short running title: Use of crushed formulation of dabrafenib and trametinibKeywords : Dabrafenib, Trametinib, BRAF, crushedData Availability: The data that support the findings of this study are available from the corresponding author upon reasonable request.

BACKGROUND: Neurocognitive deficits are an important late effect in survivors of acute lymphoblastic Leukemia(ALL). Data from low middle income countries is scarce and highly influenced by biological and cultural variations. Such data would be useful for highlighting the importance of early intervention in an already disadvantaged population. PROCEDURE: 70 consecutive survivors of childhood ALL were evaluated for neurocognitive deficits by the Indian adaptation of Wechsler Intelligence Scale for Children-Fourth Edition(WISC-INDIA). Prevalence of neurocognitive deficits was calculated based on Full Scale Intelligence Quotient(FSIQ) and scores in discrete domains like Verbal Comprehension, Perceptual Reasoning, Working Memory and Processing Speed were calculated and compared to baseline characteristics, chemotherapy and radiation dose received. RESULTS: The mean FSIQ was 86.1 ± 20.5, with significant neurocognitive deficit(FSIQ <90) being prevalent in 50%(95% CI 38% to 62%) of the cohort. The proportion of survivors with deficits in individual domains of verbal comprehension, perceptual reasoning, working memory and processing speed were 49%, 50%, 47% and 44% respectively. The odds of having deficits in neurocognitive function was higher when a child belonged to lower socioeconomic strata, had parents with less than primary school education and whose birth order was higher(All p<0.05). Age at diagnosis, current age at assessment, receiving lower or higher dose of radiotherapy, high dose methotrexate or cytarabine did not have a direct impact on neurocognitive function. CONCLUSIONS AND RELEVANCE: The current need is to develop country specific neurocognition assessment tools to initiate early screening and develop culturally appropriate preventive and rehabilitative interventions.

Background: Ineffective erythropoiesis (IE) is the most prominent feature of transfusion-dependent beta-thalassemia (TDT), which leads to extramedullary hemopoiesis. The rejection rate in allogeneic hematopoietic stem cell transplantation (HSCT) is clearly superior in heavily transfused patients (pts) with TDT accompanied by prominent IE. Therefore, a pre-transplantation treatment bridging to HSCT is often used to reduce allosensibilization and IE. Ruxolitinib (RUX) is a JAK-1/JAK-2-inhibitor and has showed its efficacy to suppress IE and the immune system. A previously published study on RUX in adult pts with TDT has revealed that this treatment significantly reduces spleen size and is well tolerated. Procedure: Ten pts (5-14 y.o.) with TDT and an enlarged spleen were enrolled. The dose of RUX was adjusted for age: for pts younger < 11 years: 40 - 100 mg/m2 and for pts >11 years: 20 - 30 mg/m2. HSCT was performed in 8 out of the 10 pts. Results: After the first 3 months of RUX therapy the spleen volume decreased in 9 out of the 10 cases by 9.1 – 67.5% (M = 35.4%) compared to the initial size (р = 0.003). The adverse events of RUX included infectious complications, moderate thrombocytopenia as well as headache and were successfully managed by reducing the dose. The outcomes of HSCT were favorable in 7 out of the 8 cases. Conclusion: RUX is promising as a short-term pre-HSCT treatment for pediatric pts with TDT and pronounced IE.

Background/Objectives: Adolescents and young adults (AYA) with sickle cell disease (SCD) face challenges related to the disease and its treatment. The Transition Readiness Assessment Questionnaire (TRAQ) is a self-report tool for assessing transition readiness for youth with special health care needs (YSHCN), including SCD. This study uses the TRAQ to understand transition readiness in patients with SCD treated at the Boston Medical Center, evaluates associations between TRAQ scores and transition outcomes (e.g., EDr, EDu), and compares TRAQ scores in this population with other YSHCN. Methods: We reviewed electronic medical records of AYA with SCD who completed the TRAQ in the pediatric hematology clinic between January 1, 2019, and March 1, 2020, and categorized healthcare encounters to calculate EDu and EDr. We used t-tests and ANOVA models to analyze mean TRAQ scores, sex, age, genotype, EDu, and EDr. Results: The sample was 45 AYA patients with SCD between 13 and 22 years old. The mean TRAQ score for the overall patient sample was 3.67. Mean TRAQ scores did not significantly vary by sex or genotype but did significantly increase with age. TRAQ scores were lower in the SCD population than in other YSHCN. TRAQ scores did not correlate to EDu or EDr. Conclusions: AYA patients with SCD have lower transition readiness than other populations of YSHCN. The age of 18 may not be the most reliable attribute of readiness, though older patients do have higher readiness. The relationship between TRAQ scores, EDr, and EDu is not clear and requires further evaluation.

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Objective: To characterize viscoelastic testing profiles of children with multisystem inflammatory syndrome in children (MIS-C). Methods: This single-center retrospective review included 30 patients diagnosed with MIS-C from January 1 to September 1, 2020. Thromboelastography (TEG) with platelet mapping was performed in 19 (63%) patients and compared to age- and gender- matched controls via Student’s t-test and Wilcoxon rank sum test. Pearson’s and Spearman correlation were used to assess relationships between TEG parameters and inflammatory markers. Results: Patients with MIS-C had abnormal TEG results compared to controls, including decreased K time (1.1 vs. 1.7 min, P<0.01), increased alpha angle (75.0 vs. 65.7 degrees, P<0.01), increased maximum amplitude (70.8 vs. 58.3 mm, P<0.01), and decreased Ly-30 (1.1 vs. 3.7%, P=0.03); consistent with increased clot formation rate and strength, and slower fibrinolysis. TEG maximum amplitude was moderately correlated with erythrocyte sedimentation rate (r=0.60, P=0.02), initial platelet count (r=0.67, P<0.01), and peak platelet count (r=0.51, P=0.03). TEG alpha angle was moderately correlated with peak platelet count (r=0.54, P=0.02). 17 (57%) patients received aspirin (ASA) and anticoagulation, 5 (17%) received only ASA, and 3 (10%) received only anticoagulation. No patients had a thrombotic event. 6 (20%) patients had a bleeding event, none of which was major. Conclusions: Patients with MIS-C had evidence of hypercoagulability on TEG. Increased erythrocyte sedimentation rate and platelets were associated with higher clot strength. Treatment with ASA or anticoagulation was well tolerated. Further multi-center study is required to characterize the rate of thrombosis and optimal thromboprophylaxis algorithm in this patient population.

Background It is important to ensure access to hydroxyurea (HU) for patients with sickle cell anemia (SCA) living in rural areas without easy access to experts in sickle cell management. The UAB Pediatric Sickle Cell program’s satellite clinics reduce the barrier of transportation to the university-based clinic. However, as compared to the university clinic, these satellite clinics do not offer immediate access to HU dosing laboratory results. Therefore, a nurse clinician calls families with HU dose adjustments after the completion of the clinic visit. This study evaluated the impact of telehealth dosing adjustments on HU laboratory and clinical response as compared to university-based patients. Methods A one year retrospective chart reviewed was performed to evaluate HU laboratory and clinical response based on clinic location and socioeconomic status for patients with SCA. We identified the number of clinic and acute care visits for one year and calculated the mean CBC and HbF values for each patient. Results We identified 107 academic center participants with SCA prescribed HU and 65 satellite clinic participants. We identified no difference in HbF, Hb, MCV, or ANC by clinic location. We also identified no difference in hospital admissions based on clinic location. Finally, mean socioeconomic indicators by zip code were lower in satellite clinic patients but not associated with a difference in HbF response. Conclusions The use of telehealth did not negatively impact laboratory response to HU. Future studies should identify novel approaches to improve access to HU among patients with SCA living in rural areas.

Multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2 infection with clinical features of Kawasaki-like disease was reported in various pediatric centers in late April 2020. Currently, cases have increased throughout the world with a range of manifestations from less to greater severity. However, hemophagocytosis has not been described in patients with MIS-C. We describe two infants diagnosed with MIS-C who presented Macrophage Activation Syndrome (MAS) with hemophagocytosis documented in the bone marrow. MIS-C can be complicated with MAS, the key features for diagnosis are splenomegaly, hypofibrinogenemia, hypertriglyceridemia and bone marrow hemophagocytosis. Cytokine storm and MAS in MIS-C may represent part of the spectrum of the disease and HScore could be of value in order to give timely and aggressive treatment.

Background: Children with hematologic malignancies, especially those who receive intensive chemotherapy, are at high risk for invasive mold infections (IMI) that confer substantial mortality. Randomized controlled trials support the use of anti-fungal prophylaxis with anti-mold activity as an optimal strategy for risk reduction in this population, but studies outlining the practical application of evidence-based recommendations are lacking. Procedure: We conducted a 15-year, single-institution retrospective review of children with hematologic malignancies treated with chemotherapy to determine the incidence of proven or probable IMI diagnosed between 2006 and 2020 and to identify the host and disease factors associated with IMI risk. We then compared the incidence and type of IMI and related factors before and after 2016 implementation of an evidence-based, risk-adapted anti-fungal prophylaxis algorithm that broadened coverage to include molds in patients at highest risk for IMI. Multivariable linear regression was used to determine factors related to IMI risk. Results: We identified 61 cases of proven or probable IMI in 1,456 patients diagnosed with hematologic malignancies during the study period (4.2%). Implementation of an anti-fungal prophylaxis algorithm reduced the IMI incidence in this population from 4.8% to 2.9%. After multivariable analysis, both Hispanic ethnicity and cancer diagnosis prior to 2016 were significantly associated with risk for IMI. Conclusion: An evidence-based, risk-adapted approach to anti-fungal prophylaxis for children with hematologic malignancies is an effective strategy to reduce incidence of IMI.