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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conferenceObject Changes in Gene Expression in Response to Red Blood Cell Transfusions in Chronically Transfused Sickle Cell Disease Patients(2019) KELLY, Shannon; DINARDO, Carla; DENG, Xutao; BELISARIO, Andre; PROIETTI, Anna Carneiro; LOUREIRO, Paula; MOTA, Rosimere Afonso; FLOR-PARK, Miriam V.; MAXIMO, Claudia; SABINO, Ester; CUSTER, Brian- 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.
- Prevalence of serologic markers of transfusion and sexually transmitted infections and their correlation with clinical features in a large cohort of Brazilian patients with sickle cell disease(2020) BLATYTA, Paula F.; KELLY, Shannon; SABINO, Ester; PREISS, Liliana; MENDES, Franciane; CARNEIRO-PROIETTI, Anna B.; RODRIGUES, Daniela de Oliveira Werneck; MOTA, Rosimere; LOUREIRO, Paula; MAXIMO, Claudia; PARK, Miriam; MENDRONE-JR, Alfredo; GONCALEZ, Thelma T.; ALMEIDA NETO, Cesar de; CUSTER, BrianBACKGROUND: Patients with sickle cell disease (SCD) often require red blood cell (RBC) transfusion for clinical complications, so may be exposed to transfusion-transmitted infections (TTIs). The prevalence of markers for human immunodeficiency virus (HIV), hepatitis C virus (HCV) and B (HBV), human T-cell lymphotropic virus (HTLV-1/2), Chagas disease, and syphilis in an SCD cohort in Brazil were studied. STUDY DESIGN AND METHODS: Clinical history, interview data, blood samples, and medical chart review data were collected during cohort enrollment from November 2013 to May 2015. Serologic markers of infection were assessed. Standard measures of statistical association were calculated, and multivariable models were developed for the most prevalent infections to identify associated factors. RESULTS: Infectionmarkers were evident in 5.2% (144/2779) of the enrolled cohort. Anti-HCV was detected in 69 (2.5%), syphilis antibodies in 34 (1.2%), anti-HTLV-1/2 in 17 (0.6%), HBV surface antigen in 13 (0.5%), Chagas disease antibodies in 13 (0.5%), and anti-HIV in 8 (0.3%) of participants. Factors associated with increased odds of being anti-HCV reactive were older age, illegal drug use, increasing number of RBCs, more than three pain crises in the previous year, and geographic location. Syphilis was associated with older age, females, and smoking history. CONCLUSION: HCV infection was more common in older patients who may have received RBCs before testing was performed on donations, suggesting possible historic transfusion transmission. The cohort showed decreasing rates of infections and a reduction in transfusion transmission markers in younger patients compared to historical literature except for syphilis, indicating contemporary reduced risk of TTI.
- 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.
- Clinical and genetic ancestry profile of a large multi-centre sickle cell disease cohort in Brazil(2018) CARNEIRO-PROIETTI, Anna B. F.; KELLY, Shannon; TEIXEIRA, Carolina Miranda; SABINO, Ester C.; ALENCAR, Cecilia S.; CAPUANI, Ligia; SILVA, Tassila P. Salomon; ARAUJO, Aderson; LOUREIRO, Paula; MAXIMO, Claudia; LOBO, Clarisse; FLOR-PARK, Miriam V.; RODRIGUES, Daniela O. W.; MOTA, Rosimere A.; GONCALEZ, Thelma T.; HOPPE, Carolyn; FERREIRA, Joao E.; OZAHATA, Mina; PAGE, Grier P.; GUO, Yuelong; PREISS, Liliana R.; BRAMBILLA, Donald; BUSCH, Michael P.; CUSTER, BrianApproximately 3500 children with sickle cell disease (SCD) are born in Brazil each year, but the burden of SCD morbidity is not fully characterised. A large, multi-centre cohort was established to characterise clinical outcomes in the Brazilian SCD population and create the infrastructure to perform genotype-phenotype association studies. Eligible patients were randomly selected from participating sites and recruited at routine visits. A biorepository of blood samples was created and comprehensive demographic and clinical outcome data were entered in a centralized electronic database. Peripheral blood genome-wide single nucleotide polymorphism (SNP) genotyping was performed using a customized Transfusion Medicine (TM) Array. A total of 2795 participants at six Brazilian sites were enrolled between 2013 and 2015. The cohort included slight predominance of children <18 years (55.9%) and females (53.0%). Haemoglobin (Hb) SS was the most common SCD genotype (70.7%), followed by HbSC (23%), S beta 0 (3.0%) and S beta+ (2.9%). SNP data from the TM Array were analysed to evaluate the genetic ancestry of the cohort and revealed significant admixture among the population. Demographics and clinical complications, stratified by age and SCD genotype, are summarized and future studies in this cohort are discussed.
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- Blood utilization and characteristics of patients treated with chronic transfusion therapy in a large cohort of Brazilian patients with sickle cell disease(2020) KELLY, Shannon; BELISARIO, Andre Rolim; RODRIGUES, Daniela O. Werneck; CARNEIRO-PROIETTI, Anna B. F.; GONCALEZ, Thelma T.; LOUREIRO, Paula; V, Miriam Flor-Park; MAXIMO, Claudia; MOTA, Rosimere Afonso; DINARDO, Carla; BRAMBILLA, Don; PREISS, Liliana; SABINO, Ester; CUSTER, BrianBACKGROUND Red blood cell (RBC) transfusions are used in sickle cell disease (SCD) to treat acute complications or as chronic transfusion therapy (CTT) to prevent severe manifestations. The objectives of this study were to describe blood utilization and adverse events (AEs) associated with RBCs in the Brazilian SCD population and compare characteristics of patients treated or not with CTT. STUDY DESIGN AND METHODS A SCD cohort was established at six Brazilian centers. Medical and blood bank records were abstracted for clinical and transfusion history. Two controls not treated with CTT matched on center, SCD genotype, sex, and age were selected for each CTT case within the cohort to compare characteristics between the two groups. RESULTS Most of the 2794-member cohort had received a transfusion (75.0% of children and 89.2% of adults) with 29.2% of patients receiving transfusion in the prior year. There were 170 (10.6%) children and 115 (9.2%) adults treated with CTT. Children not treated with CTT were more likely to have pain and acute chest hospitalizations in the prior year (25.3% vs. 11.9%, p = 0.0003; and 22.0% vs. 10.7%, p = 0.002, respectively). Both iron overload and alloimmunization were more common in CTT cases compared to controls (65.6% vs. 17.0% and 36.2% vs. 15.9%, respectively). A higher proportion of adults treated with CTT demonstrated oxygen saturation of greater than 95% compared to controls not treated (51.1% vs. 39.2%), while there was no difference in oxygenation between children treated or not. Of 4501 transfusion episodes, 28 (0.62%) AEs were reported. There was no difference in AEs associated with transfusions for acute indications versus CTT. CONCLUSION Red blood cell transfusion was common in Brazilian SCD patients, with utilization driven by CTT. Transfusion reactions were not common; however, alloimmunization and iron overload were frequent among those on CTT, highlighting the need for novel clinical strategies to mitigate these risks.
- Quality of life in pre-adolescent children with sickle cell disease in Brazil(2019) OLIVEIRA, Claudia Di Lorenzo; KELLY, Shannon; ALMEIDA-NETO, Cesar de; CARNEIRO-PROIETTI, Anna Barbara; PIASSI, Fabiana Chagas Camargos; SALOMON, Tassila; V, Miriam Flor-Park; MAXIMO, Claudia; RODRIGUES, Daniela Werneck; MOTA, Rosimere Afonso; TEIXEIRA, Carolina Miranda; LOUREIRO, Paula; SABINO, Ester Cerdeira; CUSTER, BrianSickle cell disease (SCD) affects more than 13 million people and can have a significant impact on the quality of life (QoL) of those persons. We performed a cross-sectional study to evaluate the QoL in SCD children 8-12 years old enrolled from November 2014 to March 2016 in a large multicenter cohort study in Brazil. The PedsQL (TM) SCD Module was used to evaluate QoL in 412 children from six Brazilian health centers. The mean age of participants was 10.5 years and 193(46.7%) were women. The mean global score was 60.7, with a Cronbach ' s alpha of 0.92. There were significant differences in socioeconomic demographics and treatments among participants at the six centers, but age, income, SCD genotype, and use of hydroxyurea did not significantly affect the QoL scores. After adjustment for all of these variables in a linear regression model, a significant difference was observed by site in global QoL score and the dimensions 'worry II'(beta 0 = 20.7, p < .00), 'treatment '(beta 0 = 66.8, p < .00) and communication II'(beta 0 = 45.8, p < .00). These dimensions are affected by the capacity of health professionals to provide clinical and psychological support to patients. Our results suggest that QoL of this patient population varied according the health center even adjusted by sociodemographics characteristics. Additional training of health professionals in psychological and clinical support could directly reduce patient apprehension about the disease its clinical complications.
- Hb S/beta-Thalassemia in the REDS-III Brazil Sickle Cell Disease Cohort: Clinical, Laboratory and Molecular Characteristics(2020) BELISARIO, Andre R.; CARNEIRO-PROIETTI, Anna B.; SABINO, Ester Cerdeira; ARAUJO, Aderson; LOUREIRO, Paula; MAXIMO, Claudia; FLOR-PARK, Miriam V.; RODRIGUES, Daniela D. O. W.; OZAHATA, Mina Cintho; MCCLURE, Christopher; MOTA, Rosimere Afonso; MOURA, Isabel C. Gomes; CUSTER, Brian; KELLY, ShannonWe described the clinical, laboratory and molecular characteristics of individuals with Hb S (HBB: c.20A>T)/beta-thalassemia (Hb S/beta-thal) participating in the Recipient Epidemiology and Donor Evaluation Study (REDS-III) Brazil Sickle Cell Disease cohort. HBB gene sequencing was performed to genotype each beta-thal mutation. Patients were classified as Hb S/beta(0)-thal, Hb S/beta(+)-thal-severe or Hb S/beta(+)-thal based on prior literature and databases of hemoglobin (Hb) variants. Characteristics of patients with each beta-thal mutation were described and the clinical profile of patients grouped into Hb S/beta(0)-thal, Hb S/beta(+)-thal and Hb S/beta(+)-thal-severe were compared. Of the 2793 patients enrolled, 84 (3.0%) had Hb S/beta(0)-thal and 83 (3.0%) had Hb S/beta(+)-thal; 40/83 (48.2%) patients with Hb S/beta(+)-thal had mutations defined as severe. We identified 19 different beta-thal mutations, eight Hb S/beta(0)-thal, three Hb S/beta(+)-thal-severe and eight Hb S/beta(+)-thal. The most frequent beta(0) and beta(+) mutations were codon 39 (HBB: c.118C>T) and IVS-I-6 (T>C) (HBB: c.92+6T>C), respectively. Individuals with Hb S/beta(0)-thal had a similar clinical and laboratory phenotype when compared to those with Hb S/beta(+)-thal-severe. Individuals with Hb S/beta(+)-thal-severe had significantly lower total Hb and Hb A levels and higher Hb S, white blood cell (WBC) count, platelets and hemolysis markers when compared to those with Hb S/beta(+)-thal. Likewise, individuals with Hb S/beta(+)-thal-severe showed a significantly higher occurrence of hospitalizations, vaso-occlusive events (VOE), acute chest syndrome (ACS), splenic sequestration, blood utilization, and hydroxyurea (HU) therapy.