Social determinants of health and pediatric cancer survival: A systematic review

Despite treatment advancements and improved survival, approximately 1800 children in the United States will die of cancer annually. Survival may depend on nonclinical factors, such as economic stability, neighborhood and built environment, health and health care, social and community context, and education, otherwise known as social determinants of health (SDoH). Extant literature reviews have linked socioeconomic status (SES) and race to disparate outcomes; however, these are not inclusive of all SDoH. Thus, we conducted a systematic review on associations between SDoH and survival in pediatric cancer patients. Of the 854 identified studies, 25 were included in this review. In addition to SES, poverty and insurance coverage were associated with survival. More studies that include other SDoH, such as social and community factors, utilize prospective designs, and conduct analyses with more precise SDoH measures are needed

Conditioning with Treosulfan and Fludarabine followed by Allogeneic Hematopoietic Cell Transplantation for High-Risk Hematologic Malignancies

In this prospective study 60 patients of median age 46 (range: 5-60 years), with acute myelogenous leukemia (AML; n = 44), acute lymphoblastic leukemia (ALL; n = 3), or myelodysplastic syndrome (MDS; n = 13) were conditioned for allogeneic hematopoietic cell transplantation with a treosulfan/fludarabine (Flu) combination. Most patients were considered at high risk for relapse or nonrelapse mortality (NRM). Patients received intravenous treosulfan, 12 g/m2/day (n = 5) or 14 g/m2/day (n = 55) on days −6 to −4, and Flu (30 mg/m2/day) on days −6 to −2, followed by infusion of marrow (n = 7) or peripheral blood stem cells (n = 53) from HLA-identical siblings (n = 30) or unrelated donors (n = 30). All patients engrafted. NRM was 5% at day 100, and 8% at 2 years. With a median follow-up of 22 months, the 2-year relapse-free survival (RFS) for all patients was 58% and 88% for patients without high-risk cytogenetics. The 2-year cumulative incidence of relapse was 33% (15% for patients with MDS, 34% for AML in first remission, 50% for AML or ALL beyond first remission and 63% for AML in refractory relapse). Thus, a treosulfan/Flu regimen was well tolerated and yielded encouraging survival and disease control with minimal NRM. Further trials are warranted to compare treosulfan/Flu to other widely used regimens, and to study the impact of using this regimen in more narrowly defined groups of patients

Cross-cultural adaptation and validation of a disease knowledge and self-care questionnaire for a brazilian sample of heart failure patients

To adapt a questionnaire that assesses knowledge about heart failure (HF) and self-care and to analyze its content validity and reproducibility for use in Brazil. The questionnaire was validated through translation, summary, back-translation, expert committee review, pretest and assessment of psychometric properties. The final version (14 questions) was applied at the university hospital to HF outpatients under multidisciplinary team care. Five questions showed total agreement; seven scored Kappa > 0.4; one Kappa = 0.4, and just one presented no agreement. A group of 153 patients within 1-4 years of outpatient follow-up was assessed (age 59±13, 61% male). In the knowledge assessment, right answers varied from 4 to 14 (average 9.9±2.1). Results indicate the validity of the questionnaire for use in Brazil.Se tuvo por objetivo realizar la adaptación transcultural de un cuestionario que evalúa el conocimiento sobre la insuficiencia cardíaca (IC) y el autocuidado y analizar su validez de contenido y la reproductibilidad para uso en Brasil. Se trata de un proceso de validación constituido de traducción, síntesis, retrotraducción, revisión por comité de expertos, prueba piloto y verificación de las propiedades psicométricas. La versión final adaptada con 14 preguntas fue aplicada a pacientes con IC en acompañamiento en ambulatorio con el equipo multidisciplinar de un hospital universitario. Cinco preguntas presentaron concordancia total; siete obtuvieron coeficiente Kappa > 0,4; una obtuvo Kappa 0,4 y apenas en una pregunta no hubo concordancia. Se evaluaron 153 pacientes, edad de 59±13; 61% sexo masculino; mediana de tiempo de acompañamiento en el ambulatorio 2 (1-4) años. En la evaluación del conocimiento, los aciertos variaron de cuatro a 14, promedio 9,9±2,1. Concluimos que los resultados indicaron que este cuestionario fue validado para ser usado en Brasil.Esta pesquisa teve como objetivos realizar a adaptação transcultural de um questionário que avalia o conhecimento sobre a insuficiência cardíaca (IC) e o autocuidado e analisar sua validade de conteúdo e a reprodutibilidade para uso no Brasil. O processo de validação constituiu-se de tradução, síntese, retrotradução, revisão por comitê de especialistas, pré-teste e verificação das propriedades psicométricas. A versão final adaptada com 14 questões foi aplicada a pacientes com IC em acompanhamento ambulatorial com a equipe multidisciplinar de um hospital universitário. Quanto aos resultados, cinco questões apresentaram concordância total, sete obtiveram coeficiente Kappa >0,4, uma obteve Kappa 0,4 e apenas em uma questão não houve concordância. Avaliaram-se 153 pacientes, idade de 59±13, sendo 64% sexo masculino; mediana do tempo de acompanhamento no ambulatório de 2 (1-4) anos. Na avaliação do conhecimento, os acertos variaram de quatro a 14, média 9,9±2,1. Conclui-se pelos resultados, que esse questionário foi validado para uso no Brasil

Transplantation Outcomes for Children with Hypodiploid Acute Lymphoblastic Leukemia

Children with hypodiploid acute lymphoblastic leukemia (ALL) have inferior outcomes despite intensive risk adapted chemotherapy regimens. We describe 78 children with hypodiploid ALL who underwent hematopoietic stem cell transplant (HSCT) between 1990 and 2010. Thirty nine (50%) patients had ≤ 43 chromosomes, 12 (15%) had 44 chromosomes and 27 (35%) had 45 chromosomes. Forty three (55%) patients were transplanted in first remission (CR1) while 35 (45%) were transplanted in ≥CR2. Twenty nine patients (37%) received a graft from a related donor and 49 (63%) from an unrelated donor. All patients received a myeloablative conditioning regimen. The 5-year probabilities of leukemia-free survival (LFS), overall survival (OS), relapse, and treatment related mortality (TRM) for the entire cohort were 51%, 56%, 27% and 22% respectively. Multivariate analysis confirmed that mortality risks were higher for patients transplanted in CR2 (HR 2.16, p=0.05), with chromosome number ≤43 (HR 2.15, p=0.05) and for those transplanted in the first decade of the study period (HR 2.60, p=0.01). Similarly, treatment failure risks were higher with chromosome number ≤43 (HR 2.28, p=0.04) and the earlier transplant period (HR 2.51, p=0.01). Although survival is better with advances in donor selection and supportive care, disease-related risk factors significantly influence transplantation outcomes

The genomic landscape of juvenile myelomonocytic leukemia

Juvenile myelomonocytic leukemia (JMML) is a myeloproliferative neoplasm (MPN) of childhood with a poor prognosis. Mutations in NF1, NRAS, KRAS, PTPN11 and CBL occur in 85% of patients, yet there are currently no risk stratification algorithms capable of predicting which patients will be refractory to conventional treatment and therefore be candidates for experimental therapies. In addition, there have been few other molecular pathways identified aside from the Ras/MAPK pathway to serve as the basis for such novel therapeutic strategies. We therefore sought to genomically characterize serial samples from patients at diagnosis through relapse and transformation to acute myeloid leukemia in order to expand our knowledge of the mutational spectrum in JMML. We identified recurrent mutations in genes involved in signal transduction, gene splicing, the polycomb repressive complex 2 (PRC2) and transcription. Importantly, the number of somatic alterations present at diagnosis appears to be the major determinant of outcome

Social determinants of health and pediatric cancer survival: A systematic review

Despite treatment advancements and improved survival, approximately 1800 children in the United States will die of cancer annually. Survival may depend on nonclinical factors, such as economic stability, neighborhood and built environment, health and health care, social and community context, and education, otherwise known as social determinants of health (SDoH). Extant literature reviews have linked socioeconomic status (SES) and race to disparate outcomes; however, these are not inclusive of all SDoH. Thus, we conducted a systematic review on associations between SDoH and survival in pediatric cancer patients. Of the 854 identified studies, 25 were included in this review. In addition to SES, poverty and insurance coverage were associated with survival. More studies that include other SDoH, such as social and community factors, utilize prospective designs, and conduct analyses with more precise SDoH measures are needed

DEI-05. Assessing Household Material Hardship in Children with Central Nervous System (CNS) Tumors

BACKGROUND: Household material hardship (HMH) is defined as unmet basic needs including food, heat, housing, or transportation. Researchers have documented higher rates of poor nutrition, injury, infectious disease, and hospitalization in healthy children living in families with household material hardship. Furthermore, targeted interventions exist to modify these health outcomes. However, little is known regarding the relationship between social determinants of health and their impact on overall and quality of survival for children with brain or spinal cord tumors. The current available information is based upon retrospective and secondary data sources, often limited to basic socioeconomic factors such as race and ethnicity. The objective was to describe the change in household material hardship through patient reported outcome measures from baseline to six-months and explore the association between social determinants of health, including prospective household material hardship data, and clinical outcomes among children with brain and spinal cord tumors. METHODS: We aimed to enroll 150 patients with a brain or spinal cord tumors who were followed by the Pediatric Neuro-Oncology Program at Riley Hospital for Children at IU Health. These participants were approached during their routinely scheduled clinic visits by a member of the study team. Written or verbal consent/assent was obtained, and their data was transcribed into a REDCap™ database. RESULTS: To date, we have enrolled 118 children onto this study, with 35/76 participants completing their six-month follow-up survey. In line with Kira Bona’s previous work, we have found that around 30% acknowledged one positive domain of household material hardship. Additionally, we have found that almost 40% of our cohort fall below the 200% Federal Poverty Level, which is often considered a cutpoint for lower socioeconomic status. CONCLUSIONS: We have shown that collecting prospective patient reported sociodemographic information is feasible in a busy clinical setting

The Cambridge Behavioural Inventory revised

Neurobehavioural and psychiatric symptoms are common in a range of neurodegenerative disorders with distinct profiles which are helpful in the diagnosis and monitoring of these disorders. The Cambridge Behavioural Inventory (CBI) has been shown to distinguish frontotemporal dementia (FTD), Alzheimer's disease (AD), Huntington's disease (HD) and Parkinson's disease (PD), but it is lengthy. Objective: To develop a shorter version of the 81 item CBI. Methods: CBI data from 450 participants with behavioural variant frontotemporal dementia (bv-FTD) (64), AD (96), PD (215) and HD (75) were analysed using Principal Components Analysis and measures of internal consistency (Cronbach alpha). Results: A reduced 45-item questionnaire was developed. The instrument identified distinct behavioural profiles and performed as well as the original version. Conclusions: A shorter (45 item) version of the CBI is capable of differentiating bv-FTD and AD from PD and HD. It may be useful in delineating the type and extent of problems in these disorders as well as monitoring therapeutic interventions