Childhood cancers and systems medicine.

Despite major advances in treatment, pediatric cancers in the 5-16 age group remain the most common cause of disease death, and one out of eight children with cancer will not survive. Among children that do survive, some 60% suffer from late effects such as cancer recurrence and increased risk of obesity. This paper will provide a broad overview of pediatric oncology in the context of systems medicine. Systems medicine utilizes an integrative approach that relies on patient information gained from omics technology. A major goal of a systems medicine is to provide personalized medicine that optimizes positive outcomes while minimizing deleterious short and long-term side-effects. There is an ever increasing development of effective cancer drugs, but a major challenge lies in picking the most effective drug for a particular patient. As detailed below, high-throughput omics technology holds the promise of solving this problem. Omics includes genomics, epigenomics, and proteomics. System medicine integrates omics information and provides detailed insights into disease mechanisms which can then inform the optimal treatment strategy.

Prevalence of abnormal bone density of pediatric patients prior to blood or marrow transplant.

Osteoporosis and osteopenia are long-term side effects of bone marrow transplant (BMT). The purpose of this study was to determine the prevalence of bone mineral density (BMD) abnormalities in pediatric patients prior to BMT. Forty-four pediatric patients were evaluated with DEXA scans. The average Z-score was -0.37. Thirty-six percent had abnormal BMD. Sixty-seven percent of ALL patients had abnormal BMD. Patients with non-malignant diseases were significantly more likely to have abnormal BMD. Patients with ALL had more defects than solid tumor patients. Females had more defects than males. These results demonstrate BMD defects are common in children prior to BMT, especially in patients with ALL.

Longitudinal evaluation of a pediatric palliative care educational workshop for oncology fellows.

PURPOSE: Health care providers have reported inadequate training, poor institutional support, and discomfort in managing pediatric end-of-life (EOL) issues. As a result, the transition to palliative care may be late and abrupt, and children may experience significant suffering at EOL. In this pilot study, we developed and longitudinally evaluated the efficacy of a pediatric palliative care workshop to enhance training for medical fellows. METHODS: Thirty-two pediatric oncology fellows participated in a day-long workshop on palliative care, including topics on pain and symptom management, ethics, communication, and grief. Barriers, attitudes, and knowledge with regard to pediatric palliative care were assessed immediately before the workshop and 6 and 12 months later. Knowledge was also assessed immediately after the workshop. Twenty fellows completed all assessments. RESULTS: At 6 and 12 months, staff discomfort with death and lack of knowledge were the most frequently cited barriers to providing effective EOL care. Perceived competence and comfort in EOL care improved over time, while beliefs remained relatively open and stable. Overall knowledge of pediatric palliative care improved post-workshop and at 6 months, then stabilized. Knowledge of general pediatric issues, ethics, and communication did not change, while knowledge of pain management, symptom management, and grief showed initial improvement then varying patterns of change over time. CONCLUSIONS: Although perceived competence and comfort with palliative care improved, the workshop did not uniformly produce lasting improvements in knowledge. Sustained knowledge will likely require more intensive training in palliative care. Continued research and evaluation of similar educational programs are needed.

Prolonged survival with continuous infusion topotecan: a report of 2 cases.

Two patients with solid tumors were treated with 21-day continuous infusion topotecan as palliation therapy. Case 1: A 10-year-old girl was diagnosed with progressive, metastatic hepatocellular carcinoma. Twenty-one-day continuous infusion topotecan was started and she has had a partial response. Case 2: A 17-year-old girl developed a malignant fibrous histiocytoma as a second malignant neoplasm. After partial resection and failure of multiagent chemotherapy, she started continuous infusion topotecan and was disease-free for 58 months when she died of pneumonia. These cases suggest that topotecan given as 21-day continuous infusion is efficacious for palliation care.

Mobilization of PML-RARA negative blood stem cells and salvage with autologous peripheral blood stem cell transplantation in children with relapsed acute promyelocytic leukemia.

BACKGROUND: Relapsed acute promyleocytic leukemia (APL) is treated with re-induction chemotherapy, commonly arsenic trioxide, and stem cell transplantation (SCT). The effect of arsenic trioxide on autologous peripheral blood stem cell collection is unknown. PROCEDURE: Five pediatric patients with relapsed APL had PML-RARA negative peripheral blood stem cells mobilized (four after arsenic trioxide) and underwent autologous SCT after cyclophosphamide (60 mg/kg x 2) and total body irradiation (TBI-fractionated 1,200 cGy) conditioning. RESULTS: All five patients remain in molecular remission a median of 20 months post-transplant. CONCLUSION: Autologous SCT performed during molecular remission is a treatment option for pediatric patients with relapsed APL and may provide durable leukemia-free survival without the complications of allogeneic transplantation.

Spongiform encephalopathy following allogeneic cord blood transplant.

A 6 year old boy developed a fatal, rapidly progressive encephalopathy 5 months after a matched unrelated cord blood transplant. Autopsy findings revealed spongiform changes in his brain. The clinical course of this child's illness had many findings consistent with that of a transmissible spongiform encephalopathy (TSE). Pre-mortem and post-mortem studies failed to definitively determine an etiology. Spongiform encephalopathies include the TSEs and mitochondrial encephalopathies. Both should be considered in a post-hematopoietic stem cell transplant patient who develops a progressive encephalopathy when more common etiologies are not found.

Evaluation of a pediatric palliative care educational workshop for oncology fellows.

BACKGROUND: Recent efforts have focused on improving pediatric palliative care to relieve physical and psychological suffering throughout the course of illness, as well as to improve care at the end-of-life (EOL). One area of attention has been medical training, as healthcare providers have often reported feeling ill-equipped to manage EOL issues. As a pilot study, we developed and evaluated a daylong educational workshop on pediatric palliative care for oncology fellows. PROCEDURE: Fellows (N = 32) from 20 hospitals participated in one of two workshops covering palliative care topics, such as pain/symptom management, communication, ethics, and bereavement. Training, knowledge, behavior, and attitudes regarding pediatric palliative care were assessed before the workshop, and knowledge was re-assessed immediately afterwards. RESULTS: Fellows reported a general lack of training in EOL care, and only 41% rated their education as at least "somewhat" adequate. Colleagues and personal experience were more often sources on EOL care, rather than formal classes or textbooks. Although fellows reported open attitudes toward palliative care, such as involving adolescents in decision-making, only half felt comfortable in the presence of a dying person. Fewer than half felt comfortable providing EOL care, managing families' expectations, or knowledgeable enough to discuss hospice with patients/families. Following the workshop, knowledge of palliative care increased significantly from 75 to 85% correct. CONCLUSIONS: Fellows reported open beliefs about palliative care, but acknowledged weaknesses in their training and level of competence. The workshop showed efficacy in improving knowledge, but additional research is needed to evaluate larger educational initiatives and their long-term impact on clinical services and family satisfaction.

Autologous hematopoietic stem cell transplant with melphalan and thiotepa is safe and feasible in pediatric patients with low normalized glomerular filtration rate.

Normalized glomerular filtration rate (nGFR) <60 mL/min/1.73 m(2) often precludes hematopoietic stem cell transplant (HSCT) in pediatric patients. Three patients with nGFR < 60 mL/min/1.73 m(2) enrolled on an institutional phase I trial of HSCT preparative therapy for advanced and recurrent solid tumors with escalating melphalan, ranging from 135 to 180 mg/m(2), thiotepa (600 mg/m(2)), and vincristine (2 mg/m(2)). An additional patient with low nGFR was treated with the same preparative therapy. None of the patients developed acute renal failure, excess toxicities during HSCT or delayed engraftment. These cases demonstrate that it is feasible and safe to perform HSCT in pediatric patients with low nGFR using melphalan- and thiotepa-based preparative therapy.

Mucoepidermoid carcinoma of the parotid gland as a second malignant neoplasm.

We report two second malignant neoplasms (SMNs) of the parotid gland. Patient 1 was initially diagnosed with precursor B-cell lymphoblastic lymphoma of the scalp. Eight years after her initial diagnosis she presented with a small, painless mass in the region of her parotid gland. Patient 2 was diagnosed with pre-B-cell acute lymphoblastic leukemia (ALL). Thirteen years after her initial diagnosis she presented with a painless mass in her right cheek. Both patients underwent superficial parotidectomies following excisional biopsies. Pathology revealed low-grade mucoepidermoid carcinoma (MEC) in both cases. Both patients are currently tumor free.

Prenatal presentation supports the in utero development of congenital leukemia: a case report.

Congenital leukemia is a rare disease developing within the first 4 to 6 weeks of life. We report a female infant born with facial mass and multiple subcutaneous nodules. The facial mass was discovered by ultrasound during a routine prenatal examination at the 36th week of gestation. Biopsies were consistent with the diagnosis of acute monoblastic leukemia (AML, FAB M5b). Cytogenetic studies showed 46 XX, t(11;19)(q23;p13.1), which is only found in acute monoblastic leukemia and involves the gene. The infant died at 12 days of age and autopsy revealed a large leukemic tumor burden in several body organs. The discovery of the facial mass prenatally and massive extramedullary leukemic burden support the notion of the in utero development of congenital leukemia.