The increasing intensity of high-risk neuroblastoma (HR NB) treatment over the last decades has resulted in improved survival at the expense of prolonging therapy and exposure to additional ...potentially toxic agents. Anemia and thrombocytopenia requiring transfusion are common during therapy for HR NB. Risks of cumulative red blood cell and platelet transfusions are incompletely defined in pediatric oncology patients, however, risks of transfusional iron overload are well described in other populations. This study aimed to determine the number of packed red blood cell (pRBC) and platelet transfusions throughout treatment for HR NB and how these numbers have changed with modern therapy. We performed a retrospective review of 92 patients with HR NB from June 2002 until September 2017. Patients received a median of 20 pRBC and 32 platelet transfusions. Our results demonstrated large numbers of transfusions with significantly increased blood product exposures among patients who received intensified therapy, either with additional induction chemotherapy, tandem autologous stem cell transplants, or dinutuximab plus cytokines with isotretinoin. Similar volumes of pRBC transfusions have been associated with iron overload in other populations and warrant further discussion of guidelines for long-term follow up of HR NB patients.
Conventional treatment for nasopharyngeal carcinoma (NPC) frequently fails and is accompanied by severe long-term side effects. Since virtually all undifferentiated NPCs are associated with ...Epstein-Barr virus (EBV), this tumor is an attractive candidate for cellular immunotherapy targeted against tumor-associated viral antigens. We now demonstrate that EBV-specific cytotoxic T-cell (CTL) lines can readily be generated from individuals with NPC, notwithstanding the patients' prior exposure to chemotherapy/radiation. A total of 10 patients diagnosed with advanced NPC were treated with autologous CTLs. All patients tolerated the CTLs, although one developed increased swelling at the site of pre-existing disease. At 19 to 27 months after infusion, 4 patients treated in remission from locally advanced disease remain disease free. Of 6 patients with refractory disease prior to treatment, 2 had complete responses, and remain in remission over 11 to 23 months after treatment; 1 had a partial remission that persisted for 12 months; 1 has had stable disease for more than 14 months; and 2 had no response. These results demonstrate that administration of EBV-specific CTLs to patients with advanced NPC is feasible, appears to be safe, and can be associated with significant antitumor activity.
Background/Objectives
Standard supportive care during induction therapy for high‐risk neuroblastoma (HR‐NBL) includes primary prophylactic granulocyte colony‐stimulating factor (G‐CSF) aimed at ...limiting duration of neutropenia, reducing infection risk, and minimizing treatment delays. Preclinical models suggest that G‐CSF promotes maintenance of neuroblastoma cancer stem cells and may reduce the efficacy of chemotherapy. This study's objective was to determine the safety and feasibility of administering induction chemotherapy without routine use of prophylactic G‐CSF.
Design/Methods
Children with newly diagnosed HR‐NBL received six‐cycle induction chemotherapy regimen without prophylactic G‐CSF in four cycles. G‐CSF was administered for stem cell mobilization after cycle 3 and granulocyte‐monocyte colony‐stimulating factor after cycle 5 prior to surgical resection of primary disease. The primary outcome measure was the incidence of grade 3 or higher infection. We hypothesized that the per patient infection rate would be comparable to our institutional baseline rate of 58% in patients with HR‐NBL receiving induction chemotherapy with prophylactic growth factor support. The trial used an A'Hern single‐stage design.
Results
Twelve patients with HR‐NBL received 58 cycles of chemotherapy on study. Three patients completed the entire six‐cycle regimen with no infections. Nine patients experienced grade 3 infections (bacteremia four, urinary tract infection two, skin/soft tissue infection three). No patients experienced grade 4 infections or required intensive care treatment for infection.
Conclusion
A greater than expected number of serious bacterial infections were observed during administration of induction chemotherapy for HR‐NBL without primary prophylactic G‐CSF. These results support continued prophylactic administration growth factor during induction chemotherapy.
To explore the relationships between interleukin-6 (IL-6) and soluble IL-6 receptor (sIL-6R) levels and disease extent and clinical outcome in childhood neuroblastoma.
Pretreatment peripheral blood ...(PB; n=53) and bone marrow (n=18) samples from patients with neuroblastoma were assayed by ELISA for IL-6 and sIL-6R. PB values were compared with healthy pediatric controls (n=28).
PB IL-6 levels were significantly elevated in patients with high-risk disease compared with those with low and intermediate risk disease (23.9 versus 4.3 pg/mL; P<0.001) and the normal control group (23.9 versus 3.3 pg/mL; P<0.001). Similarly, bone marrow IL-6 levels were higher in high-risk patients when compared with low- and intermediate-risk patients (15 versus 0 pg/mL; P<0.02). Other factors correlated with higher IL-6 levels were age of >18 months, bony metastases, and unfavorable histology. sIL-6R levels were not significantly correlated with disease stage. Patients with detectable PB IL-6 at diagnosis had significantly lower event-free survival rates (P<0.008). sIL-6R levels <2.5 x 10(4) pg/mL were also associated with a significantly worse event-free survival (P=0.016).
Elevated PB IL-6 levels correlated with features of high-risk neuroblastoma and poor prognosis in this population. Decreased PB sIL-6R levels correlated with the presence of metastatic disease. Further study of these markers in children with neuroblastoma seems warranted.
Abstract Background Open biopsy has been the mainstay for definitive diagnosis of neuroblastoma in pediatric patients. However, needle core biopsy may represent a faster, less invasive, and safer ...alternative to open biopsy in children. The purpose of this study was to compare safety and efficacy between needle core and open biopsy in the diagnosis of patients with intermediate- and high-risk neuroblastoma at our institution. Methods We retrospectively reviewed the medical records of children with intermediate- and high-risk neuroblastoma who underwent open or needle core biopsies from 2002 to 2010. Data collected included patient demographics, tumor size, sample adequacy for diagnosis and risk stratification (histology and cytogenetics), length of hospital stay, time to initiate chemotherapy after biopsy, need for repeat biopsy, and both intraoperative and postoperative complications. Mann-Whitney U and Fisher's exact tests were used for statistical analysis. Results During the study period, 7 patients underwent needle core primary biopsies (5 intermediate-risk primary tumors and 2 high-risk primary tumors), and 4 patients underwent needle core biopsy for metastatic tumors, whereas 21 patients had open biopsies (10, intermediate risk; 11, high risk). Median age at biopsy and median tumor size were similar in both groups. There was no significant difference in adequacy of biopsy, need for repeat biopsy, time to initiate chemotherapy, length of stay, or minor complications. The rate of major complications differed significantly between the 2 groups with 0% after needle core biopsy vs 48% after open biopsy ( P = .027). Conclusions In children, needle core biopsy is comparable in efficacy with open biopsy in the diagnosis of intermediate- and high-risk neuroblastoma with significantly lower rates of major postoperative complications. These findings warrant a larger scale evaluation of diagnostic needle core biopsies in pediatric patients with solid tumor.
The Inaugural Symposium on Childhood Cancer Health Disparities was held in Houston, Texas, on November 2, 2016. The symposium was attended by 109 scientists and clinicians from diverse disciplinary ...backgrounds with interests in pediatric cancer disparities and focused on reviewing our current knowledge of disparities in cancer risk and outcomes for select childhood cancers. Following a full day of topical sessions, everyone participated in a brainstorming session to develop a working strategy for the continued expansion of research in this area. This meeting was designed to serve as a springboard for examination of childhood cancer disparities from a more unified and systematic approach and to enhance awareness of this area of need.
The chemokine receptor, CXCR4, has been implicated in the mechanism of tumor cell metastasis to bone and bone marrow. Neuroblastoma, a cancer of children, is well known for its potential to ...metastasize to these sites. The goal of this study was to investigate whether the degree of expression of CXCR4 on cells from neuroblastoma primary tumors was related to the pattern of metastatic involvement.
Archived neuroblastoma primary tumor samples and clinical data were collected from 26 patients with newly diagnosed neuroblastoma. Expression of CXCR4 (12g5 antibody) was evaluated on formalin-fixed paraffin-embedded tumor tissues using standard immunohistochemical techniques. Each tumor was graded (grade 1 through 4) based on the proportion of cells that were positive for the 12g5 antibody. Tumor grades for CXCR4 expression were compared with clinical data from each patient.
Higher grades of expression (grade 3 and 4) were found in tumors from patients with high-stage disease (
P < .01) and in patients with bone and bone marrow metastases (
P ≤ .01). Clinical outcome in patients with tumors highly expressing CXCR4 was significantly worse (
P < .01) than in those patients with low-grade CXCR4.
CXCR4 expression in neuroblastoma primary tumors is significantly correlated with the pattern of metastatic spread.
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