Molecular profiling identifies targeted therapy opportunities in pediatric solid cancer.

To evaluate the clinical impact of molecular tumor profiling (MTP) with targeted sequencing panel tests, pediatric patients with extracranial solid tumors were enrolled in a prospective observational cohort study at 12 institutions. In the 345-patient analytical population, median age at diagnosis was 12 years (range 0-27.5); 298 patients (86%) had 1 or more alterations with potential for impact on care. Genomic alterations with diagnostic, prognostic or therapeutic significance were present in 61, 16 and 65% of patients, respectively. After return of the results, impact on care included 17 patients with a clarified diagnostic classification and 240 patients with an MTP result that could be used to select molecularly targeted therapy matched to identified alterations (MTT). Of the 29 patients who received MTT, 24% had an objective response or experienced durable clinical benefit; all but 1 of these patients received targeted therapy matched to a gene fusion. Of the diagnostic variants identified in 209 patients, 77% were gene fusions. MTP with targeted panel tests that includes fusion detection has a substantial clinical impact for young patients with solid tumors.

Sequential renal and bone marrow transplants in a child with Fanconi anemia.

FA is an autosomal recessive disorder characterized by small stature and renal abnormalities. FA can lead to progressive bone marrow failure, myelodysplastic syndrome, or acute leukemia. Using a multidisciplinary team approach, we managed a 3-yr-old boy with FA who simultaneously developed renal and hematopoietic failure. Because renal function was insufficient to support the conditioning regimen for HCT, we performed a deceased donor renal transplant in December 2012 prior to HCT with the known risk of graft-versus-graft rejection of the donor kidney. Seven months later he underwent allogeneic HCT. He obtained myeloid engraftment on day +11 and peripheral blood chimerism demonstrated all donor by day +21. He developed asymptomatic CMV reactivation and despite antirejection medications, mild skin graft-versus-host disease. He has maintained excellent renal function and remains transfusion independent with full hematopoietic recovery. He has not experienced any renal rejection episodes nor developed donor-specific antibodies toward his renal donor. Peripheral blood chimerism remains completely HCT donor. He is clinically well, now greater than two and a half yr after renal transplant and two yr after HCT. The continuing close collaboration between the Pediatric Nephrology and Bone Marrow Transplant teams is a major factor in this successful outcome.

Disseminated oligodendroglial-like leptomeningeal tumor with anaplastic progression and presumed extraneural disease: case report.

We report the neuroimaging and histopathologic findings of a 12-year-old female patient with a disseminated oligodendroglial-like leptomeningeal tumor with anaplastic progression and presumed extraneural metastatic disease. These tumors may represent distinct pathology primarily seen in pediatric patients. Neuroimaging demonstrates diffuse, progressive enhancement of the leptomeninges often with interval development of intraparenchymal lesions on follow-up. Disease is typically confined to the central nervous system, though diffuse peritoneal disease was seen in our case, possibly through metastatic seeding of the abdomen via ventriculoperitoneal shunt.

Metastatic spiradenocarcinoma occurring in an 8-year-old boy.

We recently saw the case of an 8-year-old boy with histologic findings of spiradenocarcinoma. Malignant adnexal tumors in children are exceedingly rare, and cases of spiradenocarcinoma in children are absent in the literature. We report the case of an 8-year-old boy with metastatic spiradenocarcinoma. A biopsy 2 years before his presentation at our institution was interpreted as a benign lesion, but when the lesion regrew, a repeat biopsy was performed that demonstrated ominous findings, prompting a reexcision. This reexcision demonstrated an area with significant necrosis, many mitoses, and cellular pleomorphism apparently arising out of a sharply demarcated, adjacent, lower-grade area. The histologic features of this patient's biopsies were those of spiradenocarcinoma, potentially arising out of a preexisting spiradenoma, a finding that has not been documented previously in this age group. Staging studies demonstrated multiple bilateral pulmonary nodules, which were confirmed using thoracoscopic biopsy to be metastatic disease. His chemotherapy regimen has included several cycles of cisplatin and 5-flourouracil, with ongoing disease progression of pulmonary disease. It has been 16 months since he presented to our institution (>3 years since the appearance of his initial lesion). Imaging studies demonstrate a slowly increasing size and number of pulmonary lesions. The long-term prognosis is guarded.

Prediction of CD34(+) cell yield in hematopoietic cell products from children by peripheral blood CD34(+) cell counts.

BACKGROUND AIMS: Peripheral blood stem cells (PBSC) are increasingly used as an alternative to bone marrow in autologous transplantations. In adult patients, the peripheral blood CD34(+) cell count is a good predictor of CD34(+) cell yield in apheresis. However, the determinants of stem cell yield in the pediatric population have not been well established. METHODS: We retrospectively studied 396 apheresis procedures in 301 pediatric patients. Receiver operating characteristic (ROC) curves based on pre-apheresis peripheral blood CD34(+) cell counts were generated to facilitate prediction of the optimal timing of PBSC collection. The associations between CD34(+) cell yield and age and mobilization regimen were analyzed. RESULTS: Significant differences in CD34(+) cell yield among different age groups were observed. Furthermore, higher CD34(+) cell yields were obtained in patients receiving chemotherapy as part of the mobilization regimen than those without chemotherapy. A correlation was noted between the CD34(+) cell yield and blood surrogate markers, including white blood cell count, absolute neutrophil count and pre-apheresis peripheral blood CD34(+) cell count. Cut-off values of > 35 CD34(+) cells/µL in patients < 15 years old and > 45 CD34(+) cells/µL in patients ≥ 15 years old were strong predictors of an adequate PBSC collection in one apheresis session. For clinical use, ROC curves and tables were generated to assist advance planning for PBSC collection. CONCLUSIONS: The pre-apheresis peripheral blood CD34(+) cell count is most useful in predicting PBSC yield. Our new cut-off values have better operating characteristics for children than the conventional value of 20 CD34(+) cells/µL used for adults.