Compound Heterozygous DOCK8 Mutations in a Patient with B Lymphoblastic Leukemia and EBV-Associated Diffuse Large B Cell Lymphoma.

Mutations in Dedicator of cytokinesis 8 (DOCK8) are a rare cause of combined immunodeficiency associated with atopy, infectious susceptibility, and risk for malignancy. We describe a 22-year-old male with a diagnosis of B cell lymphoblastic leukemia followed by Epstein-Barr virus (EBV)-associated diffuse large B cell lymphoma (DLBCL) with compound heterozygous mutations in DOCK8 and normal intracellular DOCK8 protein expression. Here, B cell lymphoblastic leukemia followed by EBV-associated DLBCL led to the discovery of DOCK8 deficiency. For instances of high clinical suspicion despite normal DOCK8 protein expression, additional functional testing is critical to make a diagnosis. Understanding the spectrum of DOCK8 mutants and their phenotypes will improve our understanding of DOCK8 deficiency.

Significant morbidity and mortality attributable to rothia mucilaginosa infections in children with hematological malignancies or following hematopoietic stem cell transplantation.

Rothia mucilaginosa is a gram-positive coccus that poses a diagnostic challenge and often requires DNA pyrosequencing for diagnosis as it can be easily mistaken for coagulase-negative staphylococci on initial culture results. While it is often times normal human oral and upper respiratory tract microbiota, it can be a virulent pathogen in immunocompromised patients. Most commonly, it causes bacteremia (catheter and non-catheter related) and meningitis in these patients. Our objective was to report the incidence of R. mucilaginosa infections in neutropenic children with hematological malignancies or following hematopoietic stem cell transplantation at a major children's hospital. We report 11 patients in this cohort who developed clinically significant R. mucilaginosa infections, including three deaths directly attributable to this microorganism. Three patients developed significant neurological involvement, accounting for two of the deaths, and one patient died of disseminated infection. Except for one, all patients had severe neutropenia, central line catheters, and mucosal breakdown at the time of infection. Patients who succumbed never achieved neutrophil recovery. In conclusion, R. mucilaginosa can lead to life-threatening infections in immunocompromised hosts, especially in profoundly neutropenic patients.

Relapsed hepatoblastoma confined to the lung is effectively treated with pulmonary metastasectomy.

BACKGROUND: In children diagnosed with hepatoblastoma (HB), the lungs are the most common site of metastasis at both initial presentation and relapse. Previous studies have encouraged pulmonary metastasectomy to achieve a disease-free state after resection of the primary hepatic lesion. However, there is no consensus about how to manage recurrent pulmonary metastasis. PROCEDURE: A retrospective, multi-institutional review was performed from 2005 to 2014 to identify HB patients ≤18years of age who had disease recurrence associated with pulmonary metastases alone. RESULTS: Ten patients between the ages of 8 and 33months were identified. Pulmonary metastatic recurrence was detected by measuring alpha-fetoprotein (AFP) levels and/or with CT scans of the chest. All patients subsequently underwent pulmonary metastasectomy without post-operative complications. At last follow-up, 8 patients were alive and had normal AFP levels. The 8 survivors had a median follow-up from therapy completion of 18.5months. Two patients who presented with extrapulmonary recurrence subsequently died of treatment refractory disease. CONCLUSIONS: This review supports surgical resection as a safe and, in the context of multimodal therapy, efficacious approach to manage HB patients who present with isolated pulmonary relapse.