Addressing the Gap in Research Methodologies Education in Pediatric Oncology in the Eastern Mediterranean Region.

PURPOSE: Formal training in clinical research methodologies is limited in limited-resource countries. Through collaboration among high- and middle-resource settings and in response to an identified need verbalized by regional pediatric oncology practitioners, Pediatric Oncology East & Mediterranean Group and St Jude Global developed a workshop focused on capacity building in research skills. Here, we describe its structure, implementation, and early results. METHODS: Leveraging virtual capabilities, the format included lectures and small group breakout exercise sessions, for 3 hours per day on 2 consecutive days per week for 2 consecutive weeks. Topics included basics of study design, introduction to health care statistics, research ethics, data registries, and scientific writing. Applicants were required to submit an abstract for a potential research project. Each breakout group selected one abstract for further development and presented the final version in a groupwide session. The participants' experience was evaluated through an online survey. RESULTS: Attendance included 29 registrants from 12 countries and six disciplines. Each breakout group was assigned a themed category: cohort studies, clinical trials, or registries. Critical feedback from the breakout sessions helped strengthen the selected projects, which included a retrospective study, a prospective observational study, a prospective interventional study, and a registry proposal. After the workshop, participants were invited to further develop their original abstracts, and three proposals received additional mentoring, one of which was a multi-institutional prospective study that was subsequently submitted through the Pediatric Oncology East & Mediterranean Group network for implementation. The postworkshop survey revealed an overall highly positive experience, and feedback provided potential themes for future workshops. CONCLUSION: This workshop demonstrated the potential for collaborative network partnerships in targeting research training gaps in pediatric oncology. Lessons learned will be applied to future workshops to strengthen research in limited-resource settings.

Global Access to Essential Medicines for Childhood Cancer: A Cross-Sectional Survey.

PURPOSE: Global data mapping access to essential chemotherapeutics for pediatric cancer are scarce. We report a survey of international pediatric cancer care providers' access to these medicines. METHODS: A Web-based survey was sent to pediatric oncologists registered on the Cure4Kids Web portal. We queried chemotherapeutics in the WHO Essential Medicines List for Children, from which the average proportional availability was summarized as each country's access score. In addition, we examined availability of drug packages defined by the WHO-sanctioned Expert Committee for eight pediatric cancers. We undertook a sensitivity analysis investigating how regimen access would change if the cytotoxics specified in recent agreements between the Clinton Health Access Initiative, American Cancer Society, and pharmaceutical companies were universally available. RESULTS: There were significant ( P < .001) differences in the median access scores between World Bank income groups, and 42.9% of respondents from low-income and lower middle-income countries reported suboptimal access scores. Our disease-based analysis revealed that 42.1% of patients in low-income and lower middle-income countries lacked full access to chemotherapy packages. Guaranteed availability of the cytotoxics specified in the Clinton Health Access Initiative/American Cancer Society agreements was projected to increase this regimen-based access by 1.6%, although including four additional chemotherapeutics would further increase coverage by 13.9%. CONCLUSION: This study is the first, to our knowledge, to assess worldwide variation in practical access to pediatric chemotherapy. Although mapping the proportion of available chemotherapeutics is informative, we also developed a meaningful estimate of access using disease-specific drug packages. These data provide an important baseline for continued monitoring and can aid in planning adaptive treatment guidelines that consider the trade-offs between access and outcomes.

POND4Kids: a web-based pediatric cancer database for hospital-based cancer registration and clinical collaboration.

The Pediatric Oncology Network Database, POND4Kids (www.pond4kids.org, POND), is an online, multilingual clinical database created for use by pediatric oncology units in countries with limited resources to meet various clinical data management needs including cancer registration, data collection and changes in treatment outcome. Established as a part of the International Outreach Program at St. Jude Children's Research Hospital in Memphis, Tennessee, POND aims to provide oncology units a tool to store patient data for easy retrieval and analysis and to achieve uniform data collection to facilitate meaningful comparison of information among centers. Currently, POND is being used to store clinical data on thousands of patients and measure their treatment improvement over a period of time. In 2009 POND included more than 100 pediatric oncology units; each has its own virtual private area. A case study of the UNOP Guatemala Clinic's use of POND is presented. On-going challenges at partner sites include inconsistent data collection methods, missing records, training for data managers, and slow or unreliable internet connections.

Granulocyte-macrophage colony stimulating factor and immunosuppression in the treatment of pediatric acquired severe aplastic anemia.

BACKGROUND: Immunosuppressive therapy (IS) is effective in the treatment of patients with acquired severe aplastic anemia (SAA). An enhanced myeloid response and decreased infection risk may be possible with the addition of a hematopoietic cytokine. Published data on the combination of cytokines and IS in patients with SAA are limited. The addition of G-CSF to IS shortens the time to neutrophil count recovery, but may not improve overall survival. Because GM-CSF acts differently than G-CSF, its use in combination with IS may be different. PROCEDURE: A retrospective chart review was performed on patients diagnosed with SAA and treated with IS and GM-CSF at St. Jude Children's Research Hospital. Hematologic recovery, prognostic factors, and infection data were collected. RESULTS: Eighteen patients were included in this study. The median age at diagnosis was 7.2 years (range 1.8-17.0). Ten patients (56%) had a complete response, four (22%) a partial response, and four (22%) no response. Median time to erythrocyte and platelet transfusion independence were 90 (18,243) and 64 days (18-243), and to discontinuation of treatment 287 days (90-730). Median time to partial (ANC > 500) and full (ANC > 1,500) neutrophil recovery were 41 and 51 days, respectively. Seventeen documented discrete infections occurred in six patients over 36 patient years. CONCLUSIONS: GM-CSF, in addition to IS, may shorten time to neutrophil count recovery, may be beneficial in decreasing infection rates, and may improve platelet response in patients with SAA. However, consistent with studies utilizing G-CSF, GM-CSF probably does not affect overall response rate. To fully answer whether or not cytokine therapy is of added value to IS in pediatric patients, a multi-institutional randomized trial is needed.

Natural history of moderate aplastic anemia in children.

BACKGROUND: Moderate aplastic anemia (MAA) in children is a rare, idiopathic condition of bone marrow insufficiency that can resolve spontaneously, persist for months or years, or progress to severe aplastic anemia (SAA). We evaluated the rate of progression to SAA. METHODS: We reviewed the records of 136 children referred for evaluation of bone marrow failure from 1978 to 2002 at St. Jude Children's Research Hospital. MAA was defined by a hypocellular bone marrow (<50%) and 2 or 3 cytopenias (absolute neutrophil count <1,500/mm(3), absolute reticulocyte count <40,000/mm(3), platelet count <100,000/mm(3)) lasting at least 6 weeks. RESULTS: Twenty-four patients met the criteria for MAA. At a median follow-up of 66 months (range, 10-293), 16 patients (67%) progressed to SAA, 5 (21%) had persistent MAA, and 3 (12%) had complete resolution of MAA. No risk factors for progression could be identified. CONCLUSIONS: When childhood MAA is treated with supportive care alone, 2/3 of patients progress to SAA.

Thrombocytosis in an infant with high thrombopoietin concentrations.

Patients with essential thrombocythemia (ET) usually have normal thrombopoietin (TPO) concentrations because of negative feedback from thrombocytosis. TPO mutations in familial ET cases result in increased translation efficiency with excessive TPO stimulation and thrombocytosis. The authors describe an infant with a high platelet count (1300 x 103/mm3) and an elevated TPO concentration who was successfully treated with anagrelide. Sequencing of TPO revealed no genetic cause. This case may represent a case of atypical ET in which thrombocytosis results from TPO stimulation rather than clonal proliferation. Measuring TPO concentrations may be warranted for children with unexplained extreme thrombocytosis.

Resolution of chronic hepatic sequestration in a patient with homozygous sickle cell disease receiving hydroxyurea.

Hepatic sequestration is an uncommon complication in patients with homozygous sickle cell disease. Although transfusion therapy has been effective for the acute condition, no definitive treatment of chronic hepatic sequestration has been identified. We describe a 17-year-old male patient with hemoglobin SS and chronic hepatic sequestration who was treated with long-term (60 months) hydroxyurea. After 36 months of HU therapy, the patient had both an excellent hematologic response and a resolution of hepatic sequestration, as evidenced by disappearance of clinical hepatomegaly, normalization of liver volume on serial computed tomography scans, as well as decreased sinusoidal dilatation and congestion and red blood cell sickling on liver biopsy. The findings in this case suggest that hydroxyurea may benefit patients who have unusual complications of sickle cell disease, such as chronic erythrocyte sickling in the liver.