Results of a pre-implementation analysis of Ethiopia's National Pediatric Cancer Registry.

In Ethiopia, cancer accounts for about 5.8% of total national mortality, with an estimated annual incidence of cancer of approximately 60,960 cases and an annual mortality of over 44,000 persons. This is likely an underestimation. Survival rates for pediatric malignancies are likewise suboptimal although exact figures are unknown since a national cancer registry is unavailable. The World Health Organization (WHO) provides recommendations for the creation of cancer registries to track such data. Here we describe our pharmacist-led, pre-implementation assessment of introducing an enhanced national pediatric cancer registry in Ethiopia. Our assessment project had three specific aims around which the methods were designed: 1) characterization of the current spreadsheet-based tool across participating sites, including which variables were being collected, how these variables compared to standards set by the WHO, and a description of how the data were entered and its completeness; 2) assessment of the perceptions of an enhanced registry from hospital staff; and 3) evaluation of workflow gaps regarding documentation. The hospital staff and leadership have generally positive perceptions of an enhanced pediatric cancer registry, which were further improved by our interactions. The workflow assessment revealed several gaps, which were addressed systematically using a three-phase implementation science approach. The assessment also demonstrated that the existing spreadsheet-based tool was missing WHO-recommended variables and had inconsistent completion due to the workflow gaps. A pediatric oncology summary sheet will be implemented in upcoming trips in patient charts to better summarize the patients' journey starting from diagnosis. This document will be used by the data clerks in an enhanced-spreadsheet to have a more complete data set.

Training pediatric hematologist/oncologists for capacity building in Ethiopia.

PURPOSE: A considerable barrier to global pediatric oncology efforts has been the scarcity and even absence of trained professionals in many low- and middle-income countries, where the majority of children with cancer reside. In 2013, no dedicated pediatric hematology-oncology (PHO) programs existed in Ethiopia despite the estimated annual incidence of 6000-12000 cases. The Aslan Project initiative was established to fill this gap in order to improve pediatric cancer care in Ethiopia. A major objective was to increase subspecialty PHO-trained physicians who were committed to practicing locally and empowered to lead programmatic development. METHODS: We designed and implemented a PHO training curriculum to provide a robust educational and clinical experience within the existing resource-constrained environment in Ethiopia. Education relied on visiting PHO faculty, a training attachment abroad, and extraordinary initiative from trainees. RESULTS: Four physicians have completed comprehensive PHO subspecialty training based primarily in Ethiopia, and all have remained local. Former fellows are now leading two PHO centers in Ethiopia with a combined capacity of 64 inpatient beds and over 800 new diagnoses per year; an additional former fellow is developing a pediatric cancer program in Nairobi, Kenya. Two fellows currently are in training. Program leadership, teaching, and advocacy are being transitioned to these physicians. CONCLUSIONS: Despite myriad challenges, a subspecialty PHO training program was successfully implemented in a low-income country. PHO training in Ethiopia is approaching sustainability through human resource development, and is accelerating the growth of dedicated PHO services where none existed 7 years ago.

Safety, Tolerability, and Pharmacokinetics of Liposomal Amphotericin B in Immunocompromised Pediatric Patients.

The safety, tolerability, and pharmacokinetics of the liposomal formulation of amphotericin B (L-AMB) were evaluated in 40 immunocompromised children and adolescents. The protocol was an open-label, sequential-dose-escalation, multidose pharmacokinetic study with 10 to 13 patients in each of the four dosage cohorts. Each cohort received daily dosages of 2.5, 5.0, 7.5, or 10 mg of amphotericin B in the form of L-AMB per kg of body weight. Neutropenic patients between the ages of 1 and 17 years were enrolled to receive empirical antifungal therapy or treatment of documented invasive fungal infections. The pharmacokinetic parameters of L-AMB were measured as those of amphotericin B by high-performance liquid chromatography and calculated by noncompartmental methods. There were nine adverse-event-related discontinuations, four of which were related to infusions. Infusion-related side effects occurred for 63 (11%) of 565 infusions, with 5 patients experiencing acute infusion-related reactions (7.5- and 10-mg/kg dosage levels). Serum creatinine levels increased from 0.45 ± 0.04 mg/dl to 0.63 ± 0.06 mg/dl in the overall population (P = 0.003), with significant increases in dosage cohorts receiving 5.0 and 10 mg/kg/day. At the higher dosage level of 10 mg/kg, there was a trend toward greater hypokalemia and vomiting. The area under the concentration-time curve from 0 to 24 h (AUC0-24) values for L-AMB on day 1 increased from 54.7 ± 32.9 to 430 ± 566 µg · h/ml in patients receiving 2.5 and 10.0 mg/kg/day, respectively. These findings demonstrate that L-AMB can be administered to pediatric patients at dosages similar to those for adults and that azotemia may develop, especially in those receiving ≥5.0 mg/kg/day.

Tolerance and effectiveness of nivolumab after pediatric T-cell replete, haploidentical, bone marrow transplantation: A case report.

To date, there has been a lack of pediatric experience regarding the efficacy and tolerability of immune checkpoint inhibitors after haploidentical hematopoietic stem cell transplant (HSCT). We present the case of a 22-year-old female with multiple-relapsed Hodgkin lymphoma (HL) who presented with a new relapse after haploidentical (post-haplo) HSCT. Anti-PD-1 therapy with nivolumab resulted in significant objective disease response and clinical improvement without notable side effects, including the absence of a graft-versus-host disease (GVHD). This case report suggests that immune checkpoint inhibition may be safely tolerated even in the setting of haploidentical HSCT, without triggering overt GVHD.

Population Pharmacokinetics of Liposomal Amphotericin B in Immunocompromised Children.

Liposomal amphotericin B (LAmB) is widely used in the treatment of invasive fungal disease (IFD) in adults and children. There are relatively limited pharmacokinetic (PK) data to inform optimal dosing in children that achieves systemic drug exposures comparable to those of adults. Our objective was to describe the pharmacokinetics of LAmB in children aged 1 to 17 years with suspected or documented IFD. Thirty-five children were treated with LAmB at doses of 2.5 to 10 mg kg-1 daily. Samples were taken at baseline and at 0.5- to 2.0-h intervals for 24 h after receipt of the first dose (n = 35 patients) and on the final day of therapy (n = 25 patients). LAmB was measured using high-performance liquid chromatography (HPLC). The relationship between drug exposure and development of toxicity was explored. An evolution in PK was observed during the course of therapy, resulting in a proportion of patients (n = 13) having significantly higher maximum serum concentrations (Cmax) and areas under the concentration-time curve from 0 to 24 h (AUC0-24) later in the course of therapy, without evidence of drug accumulation (trough plasma concentration accumulation ratio of <1.2). The fit of a 2-compartment model incorporating weight and an exponential decay function describing volume of distribution best described the data. There was a statistically significant relationship between mean AUC0-24 and probability of nephrotoxicity (odds ratio, 2.37; 95% confidence interval, 1.84 to 3.22; P = 0.004). LAmB exhibits nonlinear pharmacokinetics. A third of children appear to experience a time-dependent change in PK, which is not explained by weight, maturation, or observed clinical factors.

Use of reprogrammed cells to identify therapy for respiratory papillomatosis.

A patient with a 20-year history of recurrent respiratory papillomatosis had progressive, bilateral tumor invasion of the lung parenchyma. We used conditional reprogramming to generate cell cultures from the patient's normal and tumorous lung tissue. Analysis revealed that the laryngeal tumor cells contained a wild-type 7.9-kb human papillomavirus virus type 11 (HPV-11) genome, whereas the pulmonary tumor cells contained a 10.4-kb genome. The increased size of the latter viral genome was due to duplication of the promoter and oncogene regions. Chemosensitivity testing identified vorinostat as a potential therapeutic agent. At 3 months after treatment initiation, tumor sizes had stabilized, with durable effects at 15 months.

Late effects in cancer survivors: "the shared care model".

Advances continue to be made in the field of pediatric oncology ever since treatment for childhood cancer began in 1948. Since then, there has been exponential progress in the care for children with cancer as reflected in the current survival rates, which approach 90%. With such incredible survival rates, the number of childhood cancer survivors has increased significantly, with present estimates being above 300,000 in the United States alone. This success has, however, not been without cost. Long-term studies of cancer survivors have brought to light specific adverse effects of therapy, which often present years after treatment is finished, termed "late effects." Over the years, it has become apparent that monitoring for and treating these late effects of treatment is essential for the continuing health of young cancer survivors. It is now well recognized that childhood cancer survivors require long-term follow-up care given by an integrated team of qualified and invested specialty-care providers in collaboration with their primary caregivers. These teams deliver care using a risk-based approach, following a systematic plan for lifelong screening,surveillance, and prevention that incorporates risks based on the previous cancer, cancer therapy, genetic predispositions,lifestyle behaviors, and co-morbid health conditions.

Efficacy of the Survivor Health and Resilience Education (SHARE) program to improve bone health behaviors among adolescent survivors of childhood cancer.

PURPOSE: The purpose of this study is to test the efficacy of the Survivor Health and Resilience Education Program intervention--a manualized, behavioral intervention focusing on bone health behaviors among adolescent survivors of childhood cancer. METHODS: Participants were 75 teens aged 11-21 years, one or more years post-treatment, and currently cancer-free. Teens were randomized to a group-based intervention focusing on bone health or a wait-list control. Bone health behaviors were assessed at baseline and 1-month post-intervention. RESULTS: Controlling for baseline outcome measures and theoretical predictors, milk consumption frequency (p=0.03), past month calcium supplementation (p<0.001), days in the past month with calcium supplementation (p<0.001), and dietary calcium intake (p=0.04) were significantly greater at 1-month follow-up among intervention participants compared with control participants. CONCLUSIONS: The intervention had a significant short-term impact on self-reported bone health behaviors among adolescent survivors of childhood cancer. Research examining long-term intervention effectiveness is warranted.

Acute promyelocytic leukemia following chemotherapy for EBV-associated hemophagocytic lymphohistiocytosis.

We report a case of chemotherapy-related acute promyelocytic leukemia (APL) following therapy with VP-16/etoposide for EBV-associated hemophagocytic lymphohistiocytosis (HLH). A 17-month-old male presented with fever and lymphadenopathy. Bone marrow and liver biopsies showed hemophagocytosis. He responded well to chemotherapy including dexamethasone, VP-16/etoposide, and cyclosporine. One and a half year later, he developed fever and pancytopenia. Clinical work-up revealed APL with t(15;17)(q22;q12);PML-RARα translocation. He underwent chemotherapy for APL and is in remission 8 years after diagnosis. Alternative non-leukemogenic agents to effectively treat HLH would be desirable.

Can we overcome the effect of conflicts in rendering palliative care? An introduction to the Middle Eastern Cancer Consortium (MECC).

The Middle East has been experiencing an ongoing political conflict for the past several decades. This situation has been characterized by hostility often leading to violence of all sources. At times, such a conflict led to the outbreak of a military war, which was followed by an enmity between religious, ethnic, cultural, and national populations. In such environmental situations, palliative care professionals often confront major challenges including bias, mistrust, and mutual suspicion between patients and their treating clinicians. In order to overcome such obstacles, while rendering palliative care services, all professionals involved need careful planning and execution of their treatment plans. The latter is however possible, and sometimes successful even across lines of conflict, thereby promoting understanding, mutual respect, and tolerance between the involved communities and individuals.

Development of palliative-care services in a developing country: Pakistan.

Palliative care services are poorly developed in most resource-poor countries. With the increase in the number of cancer cases being diagnosed in these countries, most of whom present in advanced stages, an urgent need for palliative care is emerging. Pakistan is an example of a resource-poor country where palliative care services are in the initial phase of development.

Development and evaluation of an educational interactive CD-ROM for teens with cancer.

BACKGROUND: Cancer is the number one disease killer of children and adolescents in North America. For adolescents, this diagnosis comes at a particularly vulnerable stage. Educating adolescents with cancer from diagnosis through treatment teaches and empowers them. Increasing evidence shows that these adolescents want more information. Few educational tools exist for young cancer patients; none are interactive; therefore, a CD-ROM was developed to meet this need. PROCEDURE: Animation, voiceover, music, videos, and games were combined to develop a comprehensive multimedia CD-ROM to teach 12- to 18-year-olds with solid tumors about their disease, treatment, coping skills, and late effects in an interactive and non-threatening way. The CD-ROM was evaluated in a pre-post design with 65 subjects recruited from four pediatric oncology centers randomized to the CD-ROM or a "Handbook" containing analogous information. Pre-post questionnaires measured coping strategies, health locus of control, quality of life, cancer knowledge, and self-efficacy; post-test variables also included acceptability and use by teens, their families, and healthcare professionals. RESULTS: Teens receiving the CD-ROM were significantly more likely to increase their internal locus of control scores; however, no significant differences were observed on other measures, attributable in part to the study sample size. Among teens, acceptability was higher in the CD-ROM versus the Handbook group, but not different between the two parent groups. Pediatric oncology healthcare providers gave positive feedback on the CD-ROM. CONCLUSIONS: This CD-ROM is an innovative and engaging educational tool--the first portable interactive product with access on demand for adolescents with solid tumors.

Pediatric acute lymphoblastic leukemia and exposure to pesticides.

Organophosphates are pesticides ubiquitous in the environment and have been hypothesized as one of the risk factors for acute lymphoblastic leukemia (ALL). In this study, we evaluated the associations of pesticide exposure in a residential environment with the risk for pediatric ALL. This is a case-control study of children newly diagnosed with ALL, and their mothers (n = 41 child-mother pairs) recruited from Georgetown University Medical Center and Children's National Medical Center in Washington, DC, between January 2005 and January 2008. Cases and controls were matched for age, sex, and county of residence. Environmental exposures were determined by questionnaire and by urinalysis of pesticide metabolites using isotope dilution gas chromatography-high-resolution mass spectrometry. We found that more case mothers (33%) than controls (14%) reported using insecticides in the home (P < 0.02). Other environmental exposures to toxic substances were not significantly associated with the risk of ALL. Pesticide levels were higher in cases than in controls (P < 0.05). Statistically significant differences were found between children with ALL and controls for the organophosphate metabolites diethylthiophosphate (P < 0.03) and diethyldithiophosphate (P < 0.05). The association of ALL risk with pesticide exposure merits further studies to confirm the association.

Knowledge and Beliefs About Oncofertility and Associations with Quality of Life Among Adolescent and Young Adult Survivors of Pediatric Cancer.

PURPOSE: Adolescent and young adult (AYA) cancer survivors experience fertility and childrearing challenges in adulthood, but there is limited evidence on awareness, beliefs, and concerns about oncofertility in this population, needs for supportive resources, and associations with quality of life (QoL). METHODS: Participants were 69 AYAs aged 12-25 who were diagnosed with cancer at age 18 years or younger and ≥1 year cancer free, recruited from childhood cancer clinical records and support organizations. Participants completed self-report assessment of oncofertility knowledge and beliefs, information needs, and measures of QoL. Analyses examined associations between oncofertility-related variables and QoL. RESULTS: Knowledge and beliefs about oncofertility options were considerably low in the sample, and participants reported unmet oncofertility resource needs. In multivariable analyses, QoL was associated with beliefs valuing the importance of fertility in childhood cancer (ß = 0.87, p = 0.01) and lower information needs (ß = -1.19, p = 0.022). CONCLUSIONS: Infertility is a well-documented effect of childhood cancer treatment. Our findings indicate that clinical providers are a preferred source of information for AYA patients, and there is a need to address oncofertility concerns and challenges in this group. Research is needed to examine barriers to addressing fertility issues in childhood cancer treatment and ways to promote dialogue between providers and patients and their families.

Developing the Evidence Base in Pediatric Oncology Nursing Practice for Promoting Health-Related Quality of Life in Pediatric Oncology Patients.

Research has shown that self-esteem and hopefulness are positively related among female childhood cancer survivors (CCS) and contribute to their health-related quality of life (HRQOL). HRQOL remains a significant outcome of treatment for CCS. This study examined the relationships among self-esteem, hopefulness, and HRQOL in young adult female CCS to inform the development of evidence-based practice guidelines for pediatric oncology nursing practice. An online survey was conducted with a sample of young adult female CCS from 58 treatment centers across the United States at 4 time points: at baseline and at 6 weeks, 3 months, and 6 months after initial measurement time. The relationships between self-esteem, hopefulness, and HRQOL were statistically significant (Time 1, P = .05; Times 2, 3, and 4, P = .01) across all measurement times. These findings identify hopefulness and self-esteem as determinants of HRQOL and suggest that caring practices among pediatric oncology nurses that support psychosocial adjustment through promoting self-esteem and hopefulness have the potential to support HRQOL among young adult female CCS. These outcomes support the development of evidence-based practice guidelines to influence HRQOL outcomes among these survivors.

Treatment of immune thrombocytopenic purpura in children : current concepts.

Treatment of immune thrombocytopenic purpura (ITP), the most common bleeding disorder of childhood, is a controversial subject for most practitioners. Diagnosis and management of ITP has historically been based primarily on expert opinion rather than on evidence. Due to a paucity of carefully conducted clinical trials in children, the management of ITP varies widely, ranging from observation only, to aggressive management with intravenous immunoglobulin (IVIG), intravenous anti-D rhesus (Rh)0 immunoglobulin (IV RhIG), corticosteroids, and splenectomy. To address the controversies, the American Society of Hematology (ASH) and the British Society for Hematology (BSH) have developed ITP practice guidelines. These guidelines, based on expert opinion, differ in their recommendations for treatment. The ASH guidelines favor therapy based on a low platelet count, and the more current BSH guidelines recommend a more conservative 'wait and watch' approach. In addition to treating children with severe bleeding symptoms, there is a tendency (not evidence based) to treat early in order to prevent a life-threatening bleeding episode, including intracerebral hemorrhage. Corticosteroids are a highly effective therapy, inexpensive, and can usually increase the platelet count within hours to days. However, chronic or prolonged use is associated with toxicity. In the US, based on the knowledge of known toxicities of corticosteroids, as well as the efficacy of alternative treatments (IV RhIG, IVIG), many pediatricians prefer to treat with IVIG and IV RhIG, reserving corticosteroid treatment for serious bleeding or refractory disease. However, in the UK, for the most part, corticosteroids are used as first-line therapy in children with ITP. Splenectomy is rarely indicated in children except for those with life-threatening bleeding and chronic, severe ITP with impairment of quality of life. For children who develop chronic or refractory ITP, immunosuppressive drugs and/or chemotherapy agents may offer some promise. However, the long-term effects of these drugs in children are unknown and they should not be considered unless there is unequivocal evidence that the patient is refractory to IV RhIG, IVIG, and corticosteroids. To date, virtually all of the randomized clinical trials conducted in children with ITP have focused on platelet counts as the sole outcome measure. Only carefully designed, multicenter, randomized clinical trials comparing the effects of different treatment modalities in terms of bleeding, quality of life, adverse effects, and treatment-related costs will be able to address the controversies surrounding childhood ITP treatment and allow management of this condition to be based on scientific data rather than treatment philosophy.

Comparison of intermittent versus continuous infusion of propofol for elective oncology procedures in children.

OBJECTIVE: To compare the effects of administering propofol as a continuous infusion vs. bolus dosing in children undergoing ambulatory oncologic procedures in the pediatric intensive care unit (PICU). DESIGN: Prospective, randomized study. SETTING: Tertiary PICU in a university hospital. PATIENTS: Ambulatory oncology patients scheduled for diagnostic or therapeutic procedures with propofol anesthesia in the PICU were eligible for enrollment. INTERVENTIONS: Patients were randomly assigned to receive either continuous infusion or bolus administration of propofol in a protocol-driven manner. All patients received an initial bolus of 1.5 mg/kg, with additional 0.5 mg/kg doses until complete induction. Continuous infusions were started at 0.1 mg/kg/min and, if needed, increased 20% after a bolus of 0.5 mg/kg. Bolus group patients were given doses of 0.5 mg/kg if needed. Ramsay scores of < 5 were used as criteria for additional dosing. MEASUREMENTS AND MAIN RESULTS: Eighteen patients undergoing 40 separate procedures were enrolled during the study period. Twenty procedures each were performed with continuous or bolus administration of propofol. No differences were present between groups in demographic characteristics, induction dose and time, procedure and recovery times, or adverse events. All patients had adequate anesthesia and favorable satisfaction scores. More boluses were needed in the bolus group (8.5 +/- 4.6 vs. 5.4 +/- 2.9; p < .05). Average systolic blood pressure decreased more in the continuous infusion group (26.4% +/- 12 vs. 19.3% +/- 10; p < .05). Total propofol dose was higher in the continuous infusion group (8.0 mg/kg +/- 3.8 vs. 5.7 mg/kg +/- 2.4; p < .05). CONCLUSION: Both continuous and bolus administration of propofol provided conditions for conducting oncologic procedures that were satisfying to patients, their families, and physicians. Continuous infusions were associated with a larger total dose and greater decreases in systolic blood pressure. Physician preference is likely to dictate which method is used.