Nuanced Management of a Skull Base Tumor in the Setting of Relapsed Acute Lymphoblastic Leukemia.

Introduction Relapsed acute lymphoblastic leukemia (ALL) involving the central nervous system (CNS) is a significant issue that contributes to both morbidity and mortality. Given the poor outcomes in patients with CNS relapse, understanding how ALL involving intracranial relapse presents and is treated is critical. Here, we present a complex case of relapsed recurrent ALL in a pediatric patient. Case Report An 11-year-old patient presented with double relapse of ALL in the form of an extensive skull base lesion and again with leptomeningeal disease. For the skull base lesion, she was treated nonsurgically with chemotherapy and radiation, which led to a remarkable reduction in the size of the lesion. However, she was found to have early recurrence with leptomeningeal enhancement resulting in hydrocephalus 5 months after completing therapy. A shunt was placed successfully. Currently, she is being managed with monthly intrathecal chemotherapy with cerebrospinal fluid sampling and bone marrow biopsies every 2 months. Discussion We report the significant effect of chemotherapy and radiotherapy in reducing the size of the extensive skull base lesion, saving the patient from the risks associated with surgery. This patient's initial relapse, with a large skull base lesion that had intracranial involvement, is an unusual presentation of relapsed ALL. The additional early recurrence of leptomeningeal disease further makes this case unique and the management even more nuanced. Here, we demonstrate a multidisciplinary approach for the successful treatment of our patient, which can help guide the management of similar patients in the future.

Case Report: Treatment of the rare B-cell lymphoblastic lymphoma with scalp lesion using rotation flap.

Introduction: Leukemia is the most frequently occurring cancer in children, and lymphoblastic lymphoma (LBL) is a rare subtype. LBL are lymphoid neoplasms of B or T cell origin and are primarily treated with chemotherapy. Although cure rates among children are excellent, these patients must be monitored for relapse. Cutaneous lesions involving B-cell LBL (B-LBL) are extremely rare and here we present a patient with a worsening B-LBL scalp mass who required radical surgical excision. Case report: A 6-year-old female patient with a history of a nontender scalp mass discovered at approximately 2-3 years of age was evaluated for resection of the nodule due to its size and treatment history. The patient was originally diagnosed with follicular lymphoma by punch biopsy; excision was successfully performed on this 4 cm lesion and upon examination of the skin biopsy did we get a diagnosis of B-LBL. Reconstruction of the scalp was done through the rotation flap method. The patient's scalp healed well, and adjuvant chemotherapy was continued. There has been no reoccurrence. Discussion: Here we report the rarity of B-LBL cases involving extranodal involvement in the scalp. The most common reconstruction of scalp lesions has been using free flap from the anterolateral thigh (ALT) and latissimus dorsi (LD). Our case used the rotation flap, which has its functional and cosmetic benefits. The importance of monitoring this patient is emphasized due to the dangerous consequences of B-LBL relapse. Ultimately, our successful treatment and care of this rare case can be used as guidance for similar patients in the future.

v-SYMPHONY career development series: A collaboration to enhance professional awareness for pediatric hematology oncology trainees.

BACKGROUND: A recent survey of pediatric hematology oncology (PHO) physicians identified that a majority believe fellows are struggling to find jobs that align with their goals. Career development for trainees has historically been home institution-specific, limiting fellows' exposures to career path possibilities. The "virtual-Symposium of Pediatric Hematology/Oncology of New York (v-SYMPHONY)" instituted a tristate Career Development Series for PHO trainees to better address their needs and increase awareness of the variety of PHO career opportunities. PROCEDURE: The v-SYMPHONY Career Development Series incorporated three sessions: (a) institutional perspective, (b) individual perspectives, and (c) nuts and bolts of job search. Pre- and post-series surveys were administered to participants to measure impact. RESULTS: Forty-one fellows registered for the series and completed a pre-survey. Over half (54%) were in their third or later year of fellowship. Careers with a clinical focus were the most commonly desired career path (59%). Most had received career development advice only from faculty within their institutions (90%). Post-surveys were completed by 11 PHO fellows. Overall, 100% of respondents reported benefiting from the career sessions and recommended the series should be repeated annually. Over 90% learned new information to prepare for the job search. CONCLUSIONS: The v-SYMPHONY Career Development Series for PHO fellows across multiple institutions was established and was extremely well received by its participants. PHO fellows agreed that these sessions were beneficial in helping prepare them for the job search process. An annual regional Career Development Series is feasible and is strongly suggested to support PHO fellows.

Can you hear me now? Tools for cultivating a culture of respect, value, and appreciation within pediatric hematology, oncology, and cellular therapy.

The American Society of Pediatric Hematology/Oncology (ASPHO) conducted a workshop "Can you hear me now? Cultivating a culture of respect, value, and appreciation within pediatric hematology/oncology" at their annual meeting in May 2022 in hopes of exploring how the members can enhance wellness in a climate of increasing diversity. Initiatives in the past have focused on personal care, but it has been widely shown that administrative and institutional driven initiatives are essential to create an environment of wellness. In this interactive workshop, we discovered that 22% of participants felt their institution does not instill a culture of respect. We offered tools to the audience on multiple levels: graceful self-promotion, diversity and inclusion, and leadership perspective on creating a culture of respect to address the individual, local community, and top-down leadership approaches. Here, we offer a summary on the content of the workshop, and expand upon many of the discussion points that were raised during the workshop. We bring forth novel information on each topic individually from diverse points of view, specific to the field of pediatric hematology/oncology (PHO). We aim to highlight the importance of creating a diverse and respectful work environment in PHO in hopes of ensuring motivated, satisfied, and fulfilled healthcare providers who feel appreciated and valued.

Children and young adults hospitalized for severe COVID-19 exhibit thrombotic coagulopathy.

We report the clinical and laboratory coagulation characteristics of 27 pediatric and young adult patients (2 months to 21 years) treated for symptomatic COVID-19 at a children's hospital in the Bronx, New York, between March 1 and May 31, 2020. D-Dimer was > 0.5 µg/mL (upper limit of normal) in 25 (93%) patients at admission; 11 (41%) developed peak D-dimer > 5 µg/mL during admission. Seven (26%) patients developed venous thromboembolism: three with deep vein thrombosis and four with pulmonary embolism. Requirement of increased ventilatory support was a risk factor for thrombosis (P = 0.006). Three of eight (38%) patients on prophylactic anticoagulation developed thrombosis; however, no patients developed VTE on low-molecular-weight heparin prophylaxis titrated to anti-Xa level. Manifestation of COVID-19 disease was severe or critical in 16 (59%) patients. Four (15%) patients died of COVID-19 complications: all had comorbidities. Elevated D-dimer and increased VTE rate were observed in this young cohort, particularly in those with severe respiratory complications, suggesting thrombotic coagulopathy. More data are needed to guide thromboprophylaxis in this age group.

The Utility of 18FDG PET/CT Versus Bone Scan for Identification of Bone Metastases in a Pediatric Sarcoma Population and a Review of the Literature.

BACKGROUND: Outcome of patients with osteosarcoma (OS) and Ewing sarcoma (EWS) is dependent on presence of metastases. Imaging guidelines for OS and EWS include radiographs, computed tomography (CT), and magnetic resonance imaging for primary tumor evaluation and CT chest and bone scintigraphy (BS) for metastatic detection. 18Fluorodeoxyglucose (18FDG) positron emission tomography (PET)/CT has become more common for disease evaluation, yet there is no consensus for its use in this population. OBJECTIVE: We aimed to compare identification of osseous metastases using BS versus 18FDG PET/CT in our patient population. We hypothesized that 18FDG PET/CT is more likely to detect osseous metastases both at diagnosis and relapse. MATERIALS AND METHODS: We performed retrospective chart reviews of pediatric sarcoma patients treated at our institution from 2008 to 2019. Paired BS and 18FDG PET/CT scans were reviewed. Review of the literature was also performed. RESULTS: Thirty-three patients had paired BS and 18FDG PET/CT during diagnosis or treatment. Fifteen patients had distant osseous metastases. In the OS cohort, 8/16 patients had osseous metastases; 100% of these patients were detected on 18FDG PET/CT and 75% on BS. Thirty-one bony lesions were seen on imaging in OS patients; 100% of these were identified on 18FDG PET/CT but only 29% on BS. In the EWS cohort, 6/15 patients had osseous metastases; 100% of these patients were detected on 18FDG PET/CT and 50% on BS. Eighteen bony lesions were seen on imaging in EWS patients; 94% of these were identified on 18FDG PET/CT, but only 28% on BS. CONCLUSION: For patients in our institution with OS or EWS, osseous metastases were more likely detected using 18FDG PET/CT.

Characterization of COVID-19 disease in pediatric oncology patients: The New York-New Jersey regional experience.

PURPOSE: Pediatric oncology patients undergoing active chemotherapy are suspected to be at a high risk for severe disease secondary to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection; however, data to support this are lacking. We aim to describe the characteristics of coronavirus disease 2019 (COVID-19) in this population and also its impact on pediatric cancer care in the New York region during the peak of the pandemic. PATIENTS AND METHODS: This multicenter, retrospective study included 13 institutions. Clinical and laboratory information on 98 patients ≤21 years of age receiving active anticancer therapy, who tested positive for SARS-CoV-2 by nasopharyngeal swab polymerase chain reaction (PCR), was collected. RESULTS: Of the 578 pediatric oncology patients tested for COVID-19, 98 were positive, of whom 73 were symptomatic. Most experienced mild disease, 28 required inpatient management, 25 needed oxygen support, and seven required mechanical ventilation. There is a slightly higher risk of severe disease in males and obese patients, though not statistically significant. Persistent lymphopenia was noted in severe cases. Delays in cancer therapy occurred in 67% of SARS-CoV-2-positive patients. Of four deaths, none were solely attributable to COVID-19. The impact of the pandemic on pediatric oncology care was significant, with 54% of institutions reporting delays in chemotherapy, 46% delays in surgery, and 30% delays in transplant. CONCLUSION: In this large multi-institutional cohort, we observed that mortality and morbidity from COVID-19 amongst pediatric oncology patients were low overall, but higher than reported in general pediatrics. Certain subgroups might be at higher risk of severe disease. Delays in cancer care due to SARS-CoV-2 remain a concern.

Temporal and spatial mouse brain expression of cereblon, an ionic channel regulator involved in human intelligence.

A mild form of autosomal recessive, nonsyndromal intellectual disability (ARNSID) in humans is caused by a homozygous nonsense mutation in the cereblon gene (mutCRBN). Rodent crbn protein binds to the intracellular C-terminus of the large conductance Ca(2+)-activated K(+)channel (BK(Ca)). An mRNA variant (human SITE 2 INSERT or mouse strex) of the BK(Ca) gene (KCNMA1) that is normally expressed during embryonic development is aberrantly expressed in mutCRBN human lymphoblastoid cell lines (LCLs) as compared to wild-type (wt) LCLs. The present study analyzes the temporal and spatial distribution of crbn and kcnma1 mRNAs in the mouse brain by the quantitative real-time reverse transcriptase-polymerase chain reaction (qPCR). The spatial expression pattern of endogenous and exogenous crbn proteins is characterized by immunostaining. The results show that neocortical (CTX) crbn and kcnma1 mRNA expression increases from embryonic stages to adulthood. The strex mRNA variant is >3.5-fold higher in embryos and decreases rapidly postnatally. Mouse crbn mRNA is abundant in the cerebellum (CRBM), with less expression in the CTX, hippocampus (HC), and striatum (Str) in adult mice. The intracytoplasmic distribution of endogenous crbn protein in the mouse CRBM, CTX, HC, and Str is similar to the immunostaining pattern described previously for the BK(Ca) channel. Exogenous hemagglutinin (HA) epitope-tagged human wt- and mutCRBN proteins using cDNA transfection in HEK293T cell lines showed the same intracellular expression distribution as endogenous mouse crbn protein. The results suggest that mutCRBN may cause ARNSID by disrupting the developmental regulation of BK(Ca) in brain regions that are critical for memory and learning.

Preliminary development of a diabetic foot ulcer database from a wound electronic medical record: a tool to decrease limb amputations.

Our objective was to create a practical standardized database of clinically relevant variables in the care of patients with diabetes and foot ulcers. Numerical clinical variables such as age, baseline laboratory values, and wound area were extracted from the wound electronic medical record (WEMR). A coding system was developed to translate narrative data, culture, and pathology reports into discrete, quantifiable variables. Using data extracted from the WEMR, a diabetic foot ulcer-specific database incorporated the following tables: (1) demographics, medical history, and baseline laboratory values; (2) vascular testing data; (3) radiology data; (4) wound characteristics; and (5) wound debridement data including pathology, culture results, and amputation data. The database contains variables that can be easily exported for analysis. Amputation was studied in 146 patients who had at least two visits (e.g., two entries in the database). Analysis revealed that 19 (13%) patients underwent 32 amputations (nine major and 23 minor) in 23 limbs. There was a decreased risk of amputation, 0.87 (0.78, 1.00), using a proportional hazards model, associated with an increased number of visits and entries in the WEMR. Further analysis revealed no significant difference in age, gender, HbA1c%, cholesterol, white blood cell count, or prealbumin at baseline, whereas hemoglobin and albumin were significantly lower in the amputee group (p<0.05) than the nonamputee group. Fifty-nine percent of amputees had histological osteomyelitis based on operating room biopsy vs. 45% of nonamputees. In conclusion, tracking patients with a WEMR is a tool that could potentially increase patient safety and quality of care, allowing clinicians to more easily identify a nonhealing wound and intervene. This report describes a method of capturing data relevant to clinical care of a patient with a diabetic foot ulcer, and may enable clinicians to adapt such a system to their own patient population.