The Use of Sunitinib as Maintenance Therapy in a Pediatric Patient With a Poorly Differentiated Thymic Carcinoma.

BACKGROUND: Thymic carcinomas are rare aggressive mediastinal tumors with a median survival of 2 years. OBSERVATION: We present a pediatric patient who was diagnosed with metastatic thymic carcinoma and showed continuous improvement of his primary mass and lung metastases with a regimen of cisplatin/docetaxel followed by long-term maintenance therapy with sunitinib for over 5 years. CONCLUSIONS: This report demonstrates a long-term positive treatment effect using chemotherapy followed by sunitinib in an advanced thymic carcinoma. We are not aware of other reports of pediatric patients with metastatic thymic carcinoma treated with sunitinib maintenance who maintained a durable response for this prolonged period of time.

Multidisciplinary management of endocrinopathies and treatment-related toxicities in patients with Bloom syndrome and cancer.

The treatment of malignancy in cancer predisposition syndromes that also confer exquisite sensitivity to standard chemotherapy and radiation regimens remains a challenge. Bloom syndrome is one such disorder that is caused by a defect in DNA repair, predisposing to the development of early-onset age-related medical conditions and malignancies. We report on two patients with Bloom syndrome who responded well to chemotherapy despite significant alterations to standard protocols necessitated by hypersensitivity. Both patients experienced severe toxicities and exacerbation of endocrine comorbidities during chemotherapy. A multidisciplinary team of oncologists and endocrinologists is best suited to care for this patient population.

Rituximab therapy for patients with Langerhans cell histiocytosis-associated neurologic dysfunction.

OBJECTIVE: Since patients with langerhans cell histiocytosis and neurologic dysfunction (LCH-ND) often have incomplete treatment responses we sought a new treatment regimen. Because of clinical benefit from rituximab in multiple sclerosis patients with neurodegeneration, we evaluated its use in patients with LCH-ND. PARTICIPANTS: Eight LCH-ND patients who had failed prior therapies. METHODS: Charts of the 8 patients treated with rituximab were reviewed. Signs/symptoms and MRI responses were assessed. RESULTS: Seven of eight patients experienced some clinical improvement: gait abnormalities and tremors in four children, proprioceptive deficits in 2, and dysarthria/dysphagia in 2. Five of eight patients demonstrated improvement in intellectual/behavioral/psychological symptoms. CONCLUSION: These findings suggest that prospective studies are warranted to define safety and efficacy of rituximab for patients with LCH-ND.

Nephrotic-range proteinuria in a child with retinoic acid syndrome.

BACKGROUND: All-trans retinoic acid (ATRA) is a vitamin A derivative that is used in combination with chemotherapy to treat acute promyelocytic leukemia (APL). A serious complication of ATRA is retinoic acid syndrome (RAS), which is characterized by an inflammatory reaction with capillary leakage and myeloid cell tissue invasion that presents with cardiopulmonary symptoms and occasionally acute kidney injury. CASE-DIAGNOSIS/TREATMENT: We report the case of a 3-year-old child with APL who developed transient nephrotic-range proteinuria (max urine protein:creatinine ratio 8.6) during two episodes of RAS while on ATRA therapy. ATRA was temporarily discontinued and the patient was treated with a 3-day course of dexamethasone during each episode. He maintained normal renal function throughout and the proteinuria completely resolved. CONCLUSIONS: This is the first reported occurrence of nephrotic-range proteinuria in a child treated with ATRA. Nephrologists should be aware that RAS is a serious complication of ATRA that may lead to proteinuria.

Solitary Pediatric Osteochondroma of the Spine With Cord Compression.

Osteochondromas typically arise in the appendicular skeleton, with axial lesions occurring less commonly. Osteochondroma of the spine resulting in cord compression and symptomatic myelopathy is relatively rare. Most cases are reported in adolescents and adults. Consequently, there is a scarcity of literature regarding its occurrence in the pediatric population. We report the case of a cervical osteochondroma of C4-6 with cord compression in a nine-year-old girl. Surgical excision with laminectomy and laminotomy successfully resolved all neurologic deficits. A literature review revealed 27 cases of pediatric osteochondromas with cord compression, suggesting that these lesions are not as rare in the pediatric population as previously thought.

Hemophagocytic Lymphohistiocytosis Gene Variants in Multisystem Inflammatory Syndrome in Children.

Multisystem inflammatory syndrome in children (MIS-C) affects few children previously infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In 2020, 45 children admitted to our hospital for MIS-C underwent genetic screening with a commercial 109-immune-gene panel. Thirty-nine children were diagnosed with MIS-C, and 25.4% of the 39 MIS-C patients harbored rare heterozygous missense mutations either in primary hemophagocytic lymphohistiocytosis (pHLH) genes (LYST, STXBP2, PRF1, UNC13D, AP3B1) or the HLH-associated gene DOCK8 (four variants). We demonstrate that foamy virus introduction of cDNA for the four DOCK8 variants into human NK-92 natural killer (NK) cells led to decreased CD107a expression (degranulation) and decreased NK cell lytic function in vitro for each variant. Heterozygous carriers of missense mutations in pHLH genes and DOCK8 may serve as risk factors for development of MIS-C among children previously infected with SARS-CoV-2.

Establishing a translational genomics infrastructure in pediatric cancer: the GREAT KIDS experience.

We have recently established a biobanking and sequencing pipeline at the University of Chicago dubbed Genomics for Risk Evaluation and Anticancer Therapy in Kids. We plan to intersect family and personal history of cancer and other diseases with multidimensional genomic profiling in order to: understand how genetics may have contributed to the development of cancer for each child, and investigate the spectrum of genomic alterations within a tumor spatially (e.g., primary site vs distant metastasis) and over time (e.g., diagnosis vs relapse). This review highlights some of the practical considerations involved in creating such a program including the capacity to use our platform for multi-institutional collaborations.