Papers by Federico Antillon
BACKGROUND: Although cure rates of childhood acute lymphoblastic leukemia (ALL) have improved sig... more BACKGROUND: Although cure rates of childhood acute lymphoblastic leukemia (ALL) have improved significantly with risk-adapted therapy, stark racial disparities persist in both the incidence and treatment outcomes of ALL. There is a paucity of data describing the genetic basis of these disparities, especially in relation to modern ALL molecular taxonomy and in the context of contemporary treatment regimens. AIMS: To determine the associations of genetic ancestry with ALL biology, and the relevance of genetic ancestry to survival outcomes of modern ALL therapy. Methods: This was a multi-national genomic study of 2,428 children with ALL on front-line trials from United States, Singapore, Malaysia, and Guatemala, representing diverse populations of European, African, Native American, East Asian, and South Asian descent. We performed RNA-sequencing to characterize ALL molecular subtype and genetic ancestry, and then evaluated associations of genetic ancestries with ALL biology and treatment outcomes. Results: Of 21 ALL subtypes, 11 showed significant associations with ancestry. The frequency of somatic DUX4 gene rearrangement was positively correlated with both East Asian and South Asian ancestries; and genomic alterations in ZNF384 and PAX5 increased with East Asian ancestry. By contrast, occurrence of CRLF2 rearrangements was linked to Native American ancestry. ETV6-RUNX1 fusion became less frequent as Native American ancestry increased, with the opposite observed for ETV6-RUNX1-like ALL. There was a marked preponderance of T-ALL in children of African descent. African ancestry was also positively correlated with the prevalence of TCF3-PBX1 and MEF2D fusions. Survival outcomes differed significantly by genetic ancestry, where African and Native American ancestries were both associated with poorer event-free survival (African: HR, 2.3; 95% CI, 1.4 – 3.8; P=0.001; Native American: HR, 2.5; 95% CI, 1·0 – 5.9; P=0.044) and overall survival (African: HR, 2·4; 95% CI, 1.2 – 4.7; P=0.012 for African; Native American: HR, 3.3; 95% CI, 1.1 – 10.0; P=0.033). Importantly, even after adjusting for biological subtypes and clinical features, Native American and African ancestries remained independently associated with poor prognosis. Conclusions: ALL biology and prognosis are highly associated with genetic ancestry, pointing to a genetic basis for racial disparities in ALL. Biology-driven treatment individualization is needed to eliminate racial gaps in outcomes. Citation Format: Shawn Lee, Federico Antillon, Deqing Pei, Wenjian Yang, Kathryn G Roberts, Zhenhua Li, Meenakshi Devidas, Wentao Yang, Cesar Najera, Hai Peng Lin, Ah Moy Tan, Hany Ariffin, Cheng Cheng, William E. Evans, Stephen P. Hunger, Sima Jeha, Charles G. Mullighan, Mignon L. Loh, Allen EJ Yeoh, Ching-Hon Pui, Jun J. Yang. The impact of genetic ancestry on the biology and prognosis of childhood acute lymphoblastic leukemia [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-156.
The World Bank eBooks, Nov 1, 2015
In high-income countries (HICs), the annual incidence of childhood cancer is approximately 140 pe... more In high-income countries (HICs), the annual incidence of childhood cancer is approximately 140 per 1 million children younger than age 15 years, although estimates vary between and within countries (Parkin and others 1998). Incidence rates from low- and middle-income country (LMIC) registries are generally significantly lower, as annual rates per 1 million children of 45.6 in Namibia and 64.4 in India, respectively, illustrate (Parkin and others 1998). Some of this variation may relate to differences in environmental exposures or to biologic susceptibility. However, deficiencies in diagnosis and registration likely contribute significantly to differences in the reported incidence of cancer, both overall and of particular subtypes, such as acute leukemias (Howard and others 2008).
Cancer Medicine, Sep 21, 2022
BackgroundCommunication between providers and patients' families is an integral part of clini... more BackgroundCommunication between providers and patients' families is an integral part of clinical care. Family concern is a validated component of Pediatric Early Warning Systems (PEWS); however, little is known about the impact of PEWS on provider‐family communication.MethodsSemi‐structured interviews were conducted with 83 ward and Pediatric Intensive Care Unit (PICU) providers involved in the care of patients with deterioration at two pediatric oncology hospitals of different resource levels: St. Jude Children's Research Hospital (n = 42) in the United States and Unidad Nacional de Oncología Pediátrica (UNOP, n = 41) in Guatemala. Interviews were conducted in the participants' native language (English or Spanish), transcribed, and translated into English. Transcripts were coded by two researchers and analyzed for thematic content surrounding family communication and concern.ResultsAll participants recognized patients' families as a valuable part of the care team, particularly during events requiring escalation of care. Perceived barriers to communication included limited time spent at the bedside, and, at UNOP, language and literacy challenges which occasionally limited providers' ability to assess family concern and involve families in patient care. Despite these barriers, providers perceived PEWS improved communication by facilitating more interaction with families, allowing for relationship‐building, anticipatory guidance, and destigmatization of the PICU. PEWS assessments also allowed families to contribute to identification of deterioration.ConclusionsPEWS improve the quality of communication between providers and families by providing more opportunities for interaction, building relationships, and trust. These findings further support the use of PEWS in the care of children with cancer in hospitals of all resource‐levels.
Revista médica, Nov 25, 2019
Journal of Global Oncology, 2019
PURPOSE The educational needs of parents at the time of their child’s cancer diagnosis are often ... more PURPOSE The educational needs of parents at the time of their child’s cancer diagnosis are often unclear, and research on this topic in low- and middle-income countries is limited. This study evaluated the educational needs of families at major pediatric oncology centers in Central America and Mexico. METHODS A qualitative study involving 72 in-person interviews and 4 focus groups was conducted using a semistructured interview guide. Key informants included family members, physicians, nurses, psychosocial providers, foundation leadership, volunteers, and communication professionals. The study sites included pediatric oncology centers in El Salvador, Guatemala, Mexico, and Panama. NVivo was used for thematic analysis. RESULTS Across all sites, parents had common questions and educational needs. Questions from families focused on their child’s likelihood of dying from cancer and feelings of guilt that were based on their perception that they caused the disease. The origin of cancer, n...
Clinical Pharmacology & Therapeutics, Jan 20, 2019
Clinical Lymphoma, Myeloma & Leukemia, Sep 1, 2021
PubMed, Sep 1, 1989
From September 1984 to March 1989, 57 children received intraoperative radiotherapy as part of a ... more From September 1984 to March 1989, 57 children received intraoperative radiotherapy as part of a multidisciplinary tumor treatment. Their age ranged from 2 to 18 years. Tumor types: osteosarcoma, 21; Ewing's sarcoma, 19; soft tissue sarcomas, 6; neuroblastoma, 5; Wilm's tumor, 3; Hodgkin, 1; glioma, 1, and malignant pheochromocytoma, 1. In 44 patients the disease was localized while 13 had distant metastases. Intraoperative radiotherapy was used in 48 previously untreated patients as part of a radical treatment program and in 9 cases as an effort to rescue local failures (5 in previously irradiated areas). The intraoperative radiation field included the surgically exposed tumor or tumor bed, and the single doses ranged from 10 to 20 Gy, with 6-20 MeV electrons. With a median follow up time of 25 months (4 to 51 + months) 44 out of 57 patients are alive without local recurrence and 13 have died from tumor (6 with local progression). Intraoperative radiotherapy seems to be a feasible treatment which might promote local control in pediatric tumors.
Clinical Lymphoma, Myeloma & Leukemia, Jun 1, 2015
Fusion genes involved in acute lymphoblastic leukemia (ALL) occur mostly due to genetic and envir... more Fusion genes involved in acute lymphoblastic leukemia (ALL) occur mostly due to genetic and environmental factors, and only a limited number of studies have reported any ethnic influence. This study assesses whether an ethnic influence has an effect on the frequency of any of the four fusion genes: BCR-ABL1, ETV6-RUNX1, TCF3-PBX1, and MLL-AFF1 found in ALL. To study this ethnic influence, mononuclear cells were obtained from bone marrow samples from 143 patients with ALL. We performed RNA extraction and reverse transcription, then assessed the quality of the cDNA by amplifying the ABL1 control gene, and finally evaluated the presence of the four transcripts by multiplex polymerase chain reaction. We found 10 patients who had the BCR-ABL1 fusion gene (7%); 3 patients (2%) were TCF3-PBX1 positive; and 6 patients (4.5%) were ETV6-RUNX1 positive. The incidence of this last fusion gene is quite low when compared to the values reported in most countries. The low incidence of the ETV6-RUNX1 fusion gene found in Guatemala matches the incidence rates that have been reported in Spain and Indian Romani. Since it is known that an ethnic resemblance exists among these three populations, as shown by ancestral marker studies, the ALL data suggests an ethnic influence on the occurrence and frequency of this particular fusion gene.
Cancer, Jul 7, 2023
PurposeIn the absence of a standardized tool to assess the quality of pediatric hematology/oncolo... more PurposeIn the absence of a standardized tool to assess the quality of pediatric hematology/oncology training programs, the Education Program Assessment Tool (EPAT) was conceptualized as a user‐friendly and adaptable tool to evaluate and identify areas of opportunity, pinpoint needed modifications, and monitor progress for training programs around the world.MethodsThe development of EPAT consisted of three main phases: operationalization, consensus, and piloting. After each phase, the tool was iteratively modified based on feedback to improve its relevance, usability, and clarity.ResultsThe operationalization process led to the development of 10 domains with associated assessment questions. The two‐step consensus phase included an internal consensus phase to validate the domains and a subsequent external consensus phase to refine the domains and overall function of the tool. EPAT domains for programmatic evaluation are hospital infrastructure, patient care, education infrastructure, program basics, clinical exposure, theory, research, evaluation, educational culture, and graduate impact. EPAT was piloted in five training programs in five countries, representing diverse medical training and patient care contexts for proper validation of the tool. Face validity was confirmed by a correlation between the perceived and calculated scores for each domain (r = 0.78, p < .0001).ConclusionsEPAT was developed following a systematic approach, ultimately leading to a relevant tool to evaluate the different core elements of pediatric hematology/oncology training programs across the world. With EPAT, programs will have a tool to quantitatively evaluate their training, allowing for benchmarking with centers at the local, regional, and international level.
Clinical Lymphoma, Myeloma & Leukemia, Sep 1, 2021
Context: Although cure rates of childhood acute lymphoblastic leukemia (ALL) have improved with r... more Context: Although cure rates of childhood acute lymphoblastic leukemia (ALL) have improved with risk-adapted therapy, stark racial disparities persist in both the incidence and treatment outcomes of ALL. There is a paucity of data describing the genetic basis of these disparities, especially in relation to modern ALL molecular taxonomy and in the context of contemporary treatment regimens. Objective: Determine the associations of genetic ancestry with ALL biology and the relevance of genetic ancestry to survival outcomes of modern ALL therapy. Design: This was a multi-national genomic study of 2,428 children with ALL in front-line trials from the United States, Singapore, Malaysia, and Guatemala, representing diverse populations of European, African, Native American, East Asian, and South Asian descent. We performed RNA sequencing to characterize ALL molecular subtype and genetic ancestry and then evaluated associations of genetic ancestries with ALL biology and treatment outcomes. Results: Of 21 ALL subtypes, 11 showed significant associations with ancestry. The frequency of somatic DUX4 gene rearrangement was positively correlated with both East Asian and South Asian ancestries, and alterations in ZNF384 and PAX5 increased with East Asian ancestry. By contrast, occurrence of CRLF2 rearrangements was linked to Native American ancestry. ETV6-RUNX1 fusion became less frequent as Native American ancestry increased, with the opposite observed for ETV6-RUNX1-like. There was a marked preponderance of T-ALL in children of African descent. African ancestry was also positively correlated with the prevalence of TCF3-PBX1 and MEF2D fusions. Survival outcomes differed significantly by genetic ancestry, where African and Native American ancestries were both associated with poorer event-free survival (African: HR, 2.3; 95% CI, 1.4–3.8; P=0.001; Native American: HR, 2.5; 95% CI, 1.0–5.9; P=0.044) and overall survival (African: HR, 2·4; 95% CI, 1.2-4.7; P=0.012 for African; Native American: HR, 3.3; 95% CI, 1.1-10.0; P=0.033). Importantly, even after adjusting for biological subtypes and clinical features, Native American and African ancestries remained independently associated with poor prognosis. Conclusions: ALL biology and prognosis are highly associated with genetic ancestry, pointing to a genetic basis for racial disparities in ALL. Biology-driven treatment individualization is needed to eliminate racial gaps in outcomes.
Frontiers in Public Health
Infectious complications remain major contributors to adverse outcomes in patients treated for no... more Infectious complications remain major contributors to adverse outcomes in patients treated for non-communicable disease, particularly in resource limited settings. We performed a 5-year retrospective study of primary bloodstream infections at a dedicated pediatric oncology center in Guatemala. Two hundred and twelve episodes occurring in 194 unique patients qualified for inclusion. Patients required intensive care unit admission in 55% of episodes and death occurred in 24% of episodes. Despite subspecialty support in infectious diseases, poor outcomes, including prolonged hospitalization and mortality, were frequent. Our findings suggest that investments in laboratory and clinical data collection are critical to understanding the contributors to poor outcomes and therefore to improving the quality of bloodstream infection management in resource limited settings.
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Papers by Federico Antillon