Thomas W. McLean

Religiosity is Associated With the Use of Complementary Medical Therapies by Pediatric Oncology Patients

Purpose To determine the prevalence of complementary and alternative medicine (CAM) use in pediatric oncology patients, the types of CAM used, and the factors associated with the use of CAM. Patients and Methods A questionnaire regarding CAM use was administered to patients/families seen in the pediatric oncology clinic at Wake Forest University Baptist Medical Center over a 12-month period. Results Based on 195 completed questionnaires, 91 (47%) patients reported use of CAM since diagnosis. Among CAM users, the most commonly used CAM therapies were faith healing, megavitamins/minerals, massage, other dietary supplements, relaxation techniques, and herbal medicines/teas. Forty-one percent of CAM users had not discussed CAM use with their physician(s). In bivariate analysis, CAM use was not associated with age at the time of survey, time since diagnosis, sex, race, parental education, or family income. A trend was noted between CAM use and older age at diagnosis. Families who reported themselves to be “very” religious were more likely to use CAM than those that are “somewhat” or “not at all” religious. Conclusions Use of CAM is common among pediatric oncology patients and often is not discussed with the treating physician(s). Patients from very religious families are more likely to use CAM.

Pediatric genitourinary tumors.

Purpose of review We will review the 2007/2008 literature on pediatric genitourinary tumors. Recent findings Newly identified constitutional epigenetic defects in Wilms tumor genes extend the understanding of Wilms tumor risk in children lacking syndromic features, and add to the complexity of the pathogenesis of these tumor suppressor genes. Pediatric renal cell carcinoma has distinct molecular characteristics and clinical associations from the adult counterpart. The pathway from PAX3-FKHR translocation to the development of rhabdomyosarcoma tumors has been further elucidated. Summary Therapeutic strategies continue to be driven by developments in molecular diagnostics in pediatric genitourinary tumors.

Recent Steroid Therapy Increases Severity of Varicella Infections in Children With Acute Lymphoblastic Leukemia

Objective. The varicella-zoster virus (VZV) continues to be a dangerous pathogen to immunocompromised children. Children with acute lymphoblastic leukemia (ALL) are treated with intermittent steroid therapy. This study was undertaken to examine the relationship between steroid therapy for ALL and severity of varicella infection. Methods. We performed a retrospective review of patients who were on Pediatric Oncology Group Protocol 9201 and had a history of varicella infection. Pediatric Oncology Group 9201 is a phase III study for the treatment of children with lesser risk ALL diagnosed between 1992 and 1999. Cases of varicella were coded 1 to 5 on the basis of severity: grade 1 caused minimal to no symptoms, grade 2 caused mild to moderate symptoms that did not require hospitalization, grade 3 caused symptoms severe enough to require hospitalization and intravenous acyclovir, grade 4 caused severe disease that had complications or that required intensive care, and grade 5 resulted in death. Results. Of 697 enrolled patients, 110 (15.8%) developed primary varicella; 59% of these were male. For analysis, disease grade was dichotomized into nonsevere (grades 1 and 2) and severe (grades 3, 4, and 5). Of the 110 patients, 56 had nonsevere disease; 54 had severe disease, including 2 deaths. Of the patients whose varicella was diagnosed within 3 weeks of receipt of prednisone, 70% had severe infection, whereas only 44% of those who had not received prednisone within 3 weeks had severe infection. The odds ratio for having a severe infection within 3 weeks of prednisone versus >3 weeks is 2.9 (95% confidence interval: 1.1–7.9). By multivariate analysis, older age at ALL diagnosis, years from ALL diagnosis to VZV diagnosis, and VZV diagnosis within the 4-week period of interest (during or within 3 weeks of prednisone therapy) all were independently associated with an increased risk for severe infection. Conclusions. This study represents the largest study to date of varicella in children with ALL and provides convincing evidence that prednisone therapy during the VZV incubation period significantly increases the risk for developing severe varicella infection. In addition, older age is associated with more severe infection. Despite the varicella vaccine and a dropping incidence of primary infections, VZV remains a dangerous pathogen for pediatric patients with ALL. With the possible exception of induction therapy, patients who are on ALL therapy and are exposed to varicella should have steroid therapy delayed until after the VZV incubation period. These findings may have implications for other diseases that are treated with corticosteroids.

Late events in pediatric patients with Ewing sarcoma/primitive neuroectodermal tumor of bone: the Dana-Farber Cancer Institute/Children's Hospital experience.

The outcome for 82 pediatric patients with Ewing sarcoma (ES) and primitive neuroectodermal tumor (PNET) of bone is reported; the patients were treated at the Dana-Farber Cancer Institute (DFCI) and Childrens Hospital (CH) in Boston, MA (USA) from 1971-1988. The charts of all patients with ES/PNET of bone treated during this period were reviewed for disease status, therapy, sites of relapse, information on second malignancies, and survival status. Eighty-two patients with ES/PNET of bone treated at DFCI/CH were identified. The 10-year event-free survival (EFS) rates were 12% (95% confidence interval [CI] 0, 27%) and 38% (95% CI 26, 51%) for patients with and without metastases, respectively (P = 0.002); the overall survival (OS) rates were 17% (95% CI 1, 33%) and 48% (95% CI 35, 61%) for patients with and without metastases (P = 0.001). Median follow-up for surviving patients is 10.2 years. Primary site in the pelvis also was associated with a poor outcome for patients with no metastatic disease (P = 0.006 OS, P = 0.03 EFS). Thirty-one patients survived in first remission at least 5 years from diagnosis, and of these, five experienced relapse of original disease, and five experienced secondary malignancies. Pediatric patients treated for ES/PNET of bone remain at risk for life-threatening events into the second decade of follow-up. After 5 years, the risk of second malignant neoplasm is at least as high as the risk of late relapse. Prolonged follow-up of patients with ES and PNET of bone is indicated.

Hemophagocytic Lymphohistiocytosis Complicating Influenza A Infection

During the influenza A (H3N2) season of 2003–2004, several influenza-related complications and deaths were reported in children. Hemophagocytic lymphohistiocytosis complicating influenza A infection is very rare. We report a 3-year-old girl who presented with severe pneumonia and hemophagocytic lymphohistiocytosis associated with influenza A infection. Clinicians should be aware of hemophagocytic syndrome as a serious complication of influenza A infection.

Mutations in the transcriptional repressor REST predispose to Wilms tumor

Wilms tumor is the most common childhood renal cancer. To identify mutations that predispose to Wilms tumor, we are conducting exome sequencing studies. Here we describe 11 different inactivating mutations in the REST gene (encoding RE1-silencing transcription factor) in four familial Wilms tumor pedigrees and nine non-familial cases. Notably, no similar mutations were identified in the ICR1000 control series (13/558 versus 0/993; P < 0.0001) or in the ExAC series (13/558 versus 0/61,312; P < 0.0001). We identified a second mutational event in two tumors, suggesting that REST may act as a tumor-suppressor gene in Wilms tumor pathogenesis. REST is a zinc-finger transcription factor that functions in cellular differentiation and embryonic development. Notably, ten of 11 mutations clustered within the portion of REST encoding the DNA-binding domain, and functional analyses showed that these mutations compromise REST transcriptional repression. These data establish REST as a Wilms tumor predisposition gene accounting for ∼2% of Wilms tumor.

Catheter-related bacteremia due to Roseomonas species in pediatric hematology/oncology patients

Roseomonas is a newly described genus of pink‐pigmented, gram‐negative bacteria. Human infections caused by Roseomonas species are very rare. We report two cases of central venous catheter‐related bacteremia associated with Roseomonas species (one case with R. gilardii and one with R. fauriae), and review the clinical spectrum of previously reported cases in the literature. Clinicals should be aware that Roseomonas species may cause serious infections in children. Pediatr Blood Cancer 2006, 46:514–516.

Spontaneous tumor lysis syndrome in a child with T-cell acute lymphoblastic leukemia†

We report a 5‐year‐old female who presented with unexplained acute renal failure (ARF) and hyperuricemia and who was subsequently diagnosed of T‐cell acute lymphoblastic leukemia (ALL). Peripheral smear was initially unremarkable. She required hemodialysis. Two weeks later, peripheral smear showed 40% blasts and bone marrow demonstrated T‐cell ALL. Our case was the fifth and the youngest case of ALL with spontaneous tumor lysis syndrome. However, in contrast to previous reports in ALL or acute myeloid leukemia, our patient did not have blasts noted on periphereal blood smear and her white blood cell count and serum lactate dehydrogenase level were normal on admission, a time when dialysis‐dependent ARF and severe hyperuricemia were present. Occult hematologic malignancy should be considered in cases of ARF and hyperuricemia of unknown etiology even when peripheral hematologic findings are not informative. Pediatr Blood Cancer 2010;54:773–775.

Langerhans cell histiocytosis and hypercalcemia : Clinical response to indomethacin

Purpose: Hypercalcemia is a known complication of childhood malignancies but has never been reported to be associated with Langerhans cell histiocytosis (LCH) in a pediatric patient. Patients and Methods: We describe an infant with multisystem LCH who developed hypercalcemia on two occasions. After being placed on indomethacin, the hypercalcemia did not recur despite disease progression. Conclusion: Hypercalcemia may complicate LCH. If it is demonstrated, indomethacin should be considered as a treatment.

Spontaneous regression of langerhans cell histiocytosis in a neonate with multiple bony lesions.

We report the case of a newborn with Langerhans cell histiocytosis involving the skin and multiple bones. All lesions resolved without therapy. This case underscores the benefits of a conservative approach in the absence of risk organ involvement.