MIRIAM VERONICA FLOR PARK
Projetos de Pesquisa
Unidades Organizacionais
Instituto da Criança, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/31 - Laboratório de Genética e Hematologia Molecular, Hospital das Clínicas, Faculdade de Medicina
LIM/31 - Laboratório de Genética e Hematologia Molecular, Hospital das Clínicas, Faculdade de Medicina
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- How Ancestry Influences the Chances of Finding Unrelated Donors: An Investigation in Admixed Brazilians(2020) NUNES, Kelly; AGUIAR, Vitor R. C.; SILVA, Marcio; SENA, Alexandre C.; OLIVEIRA, Danielli C. M. de; DINARDO, Carla L.; KEHDY, Fernanda S. G.; TARAZONA-SANTOS, Eduardo; ROCHA, Vanderson G.; CARNEIRO-PROIETTI, Anna Barbara F.; LOUREIRO, Paula; FLOR-PARK, Miriam V.; MAXIMO, Claudia; KELLY, Shannon; CUSTER, Brian; WEIR, Bruce S.; SABINO, Ester C.; PORTO, Luis Cristovao; MEYER, DiogoA match of HLA loci between patients and donors is critical for successful hematopoietic stem cell transplantation. However, the extreme polymorphism of HLA loci - an outcome of millions of years of natural selection - reduces the chances that two individuals will carry identical combinations of multilocus HLA genotypes. Further, HLA variability is not homogeneously distributed throughout the world: African populations on average have greater variability than non-Africans, reducing the chances that two unrelated African individuals are HLA identical. Here, we explore how self-identification (often equated with ""ethnicity"" or ""race"") and genetic ancestry are related to the chances of finding HLA compatible donors in a large sample from Brazil, a highly admixed country. We query REDOME, Brazil's Bone Marrow Registry, and investigate how different criteria for identifying ancestry influence the chances of finding a match. We find that individuals who self-identify as ""Black"" and ""Mixed"" on average have lower chances of finding matches than those who self-identify as ""White"" (up to 57% reduction). We next show that an individual's African genetic ancestry, estimated using molecular markers and quantified as the proportion of an individual's genome that traces its ancestry to Africa, is strongly associated with reduced chances of finding a match (up to 60% reduction). Finally, we document that the strongest reduction in chances of finding a match is associated with having an MHC region of exclusively African ancestry (up to 75% reduction). We apply our findings to a specific condition, for which there is a clinical indication for transplantation: sickle-cell disease. We show that the increased African ancestry in patients with this disease leads to reduced chances of finding a match, when compared to the remainder of the sample, without the condition. Our results underscore the influence of ancestry on chances of finding compatible HLA matches, and indicate that efforts guided to increasing the African component of registries are necessary.
- Identification and Characterization of Hematopoietic Stem Cell Transplant Candidates in a Sickle Cell Disease Cohort(2019) V, Miriam Flor-Park; KELLY, Shannon; PREISS, Liliana; CUSTER, Brian; CARNEIRO-PROIETTI, Anna B. F.; ARAUJO, Aderson S.; LOUREIRO, Paula; MAXIMO, Claudia; RODRIGUES, Daniela O. W.; MOTA, Rosimere A.; SABINO, Ester C.; ROCHA, VandersonSickle cell disease (SCD) is associated with significant morbidity, and allogeneic hematopoietic stem cell transplantation (HSCT) remains the primary curative treatment. Recently, the Brazilian Ministry of Health released a regulation that required the publically funded healthcare system to pay for HSCT for SCD patients with defined indications. We used an existing 2794-member SCD cohort established during 2013 to 2015 to characterize candidates for HSCT and estimate the number of possible donors. Of 2064 patients with SC anemia (SCA), 152 of 974 children (16%) and 279 of 1090 adults (26%) had at least 1 HSCT indication. The most common indication for transplant was stroke (n = 239) followed by avascular necrosis (n = 96), priapism (n = 82), cerebrovascular disease (n = 55), >2 vaso-occlusive episodes (n = 38), alloantibodies and chronic transfusion therapy (n = 18), and >2 acute chest syndrome episodes (n = 11). Increasing age, number of transfusions, abnormal transcranial Doppler, retinopathy, dactylitis, and use of hydroxyurea were more frequent in the 152 children with an indication for HSCT compared with 822 without (P < .001). Of 152 children and 279 adults meeting the eligibility definition, 77 (50%) and 204 (73%), respectively, had at least 1 non-SCD full sibling who could potentially serve as a donor. In conclusion, in a large cohort of SCA patients, 16% of children and 26% of adults had at least 1 indication for HSCT; these indications were associated with the severity of the disease. This study provides clinical data necessary for estimating the costs and infrastructure that would be required to implement HSCT in a public healthcare system. (C) 2019 American Society for Transplantation and Cellular Therapy.
- Is Severity Score Associated With Indication for Hematopoietic Stem Cell Transplantation in Individuals With Sickle Cell Anemia?(2022) V, Miriam Flor-Park; OZAHATA, Mina Cintho; MOURA, Isabel Cristina Gomes; BLATYTA, Paula; KELLY, Shannon; OLIVEIRA, Claudia di Lorenzo; CAPUANI, Ligia; BELISARIO, Andre Rolim; CARNEIRO-PROIETTI, Anna B. F.; ARAUJO, Aderson S.; LOUREIRO, Paula; MAXIMO, Claudia; RODRIGUES, Daniela O. W.; MOTA, Rosimere A.; SABINO, Ester; CUSTER, Brian; ROCHA, VandersonManifestations of sickle cell disease (SCD) begin early in childhood and cause morbidity and decreased life expectancy. Hematopoietic stem cell transplantation (HSCT) is curative but associated with risk of mortality attributable to the transplant. This risk should be counterbalanced with SCD morbidity and mortality. A severity score using a Bayesian network model was previously validated to predict the risk of death in adult individuals with SCD. The objective of this study is to calculate the severity scores of participants in a multicenter cohort of Brazilians with SCD, using a previously published Bayesian network-derived score, associated with risk of death and then compare the severity scores between participants with and without an indication for HSCT as defined by the Brazilian Ministry of Health (MoH) criteria. This is an observational, retrospective study. We analyzed 2063 individuals with sickle cell anemia from the Recipient Epidemiology and Donor Evaluation Study-Ill Brazil SCD cohort and applied a Bayesian network-derived score to compare candidates and non-candidates for HSCT according to the Brazilian MoH transplant criteria. Classical statistical methods were used to analyze data and make comparisons. We compared severity scores between cohort members with (n = 431) and without (n = 1632) HSCT indications according to Brazilian MoH. Scores were not different in adult participants with >= 1 HSCT indication when compared to those with no indication (mean 0.342 versus 0.292; median 0.194 versus 0.183, P = .354) and receiver operating characteristic curves did not demonstrate an obvious threshold to differentiate participants with or without HSCT indications. Severity score may predict risk of death but does not differentiate HSCT candidates. Current indications should be evaluated to ensure that patients with more severe disease who might benefit from HSCT are appropriately identified.
conferenceObject Characterization of Candidates for Hematopoietic Stem Cell Transplantation in a Sickle Cell Disease Cohort and Estimation of Number of Potential Donors for Candidates(2018) FLOR-PARK, Miriam Veronica; KELLY, Shannon; PREISS, Liliana; CUSTER, Brian; CARNEIRO-PROIETTI, Anna Barbara; ARAUJO, Aderson; LOUREIRO, Paula; MAXIMO, Claudia; RODRIGUES, Daniela Werneck; AFONSO, Rosimere; SABINO, Ester; ROCHA, Vanderson