Brazilian Transplant Research Articles

Recent cardiac rehabilitation and its impact on cardiopulmonary exercise test variables in Brazilian cardiac transplant recipients

Abstract Introduction Heart transplantation (HTx) is an option for restoring the functional capacity of individuals with end-stage heart failure (HF). Cardiac rehabilitation (CR) plays an important role in improving variables related to cardiopulmonary exercise testing (CPET) in post-HTx patients. Purpose To evaluate whether CR is effective in improving CPET variables in Brazilian patients post-recent HTx compared to a Control Group (CG). Methods Retrospective comparative study composed of two groups: CR group (CRG) and CG. These recent HTx patients (aged 14 to 73 years) initiated CR within 150 days and were recruited from an HTx outpatient clinic at a south Brazilian public university hospital between 2014 and 2023. CPET was performed at three different times: pre-HTx (Time 01), post-recent HTx (Time 02), and post-CR or post-follow-up for CG (Time 03). This study was approved by the Institutional Review Board (protocol No. 20180651). Statistical analysis used Generalized Estimating Equations with alpha ≤ 0.05, and the mean difference (MD) data were presented along with 95% confidence interval (CI). Results CRG (n=18) had a mean age of 47.3±15.6 years and CG (n=11) 48.6±12.5 years (P=0.81). The mean time to start CRG was 62.2±9.6 days (minimum: 21; maximum: 147). There was an interaction for the Group*Time factor for the following CPET variables: VO2peak (P=0.039); VEmax (P=0.009); VO2 on second ventilatory threshold (P<0.001); HR on VT2 (P=0.030) and T½ (P=0.002). The main results are summarized in Table 1. We highlight that there was a difference in the comparison between groups at Time 03 for the variable VO2peak: MD: 5.16 ± 1.95 (95% CI: 1.3 to 9.0; P = 0.008), favorable to CRG. Conclusion Early CR after very recent HTx significantly increase peak VO2peak, VEmax, T½ and VO2 and HR at the VT2 compared to the control group (CG).

P.503: The importance of a Brazilian specialized transplant center in a high-complexity university hospital: An 11 years overview of the outcomes.

P.503: The importance of a Brazilian specialized transplant center in a high-complexity university hospital: An 11 years overview of the outcomes.

CURRENT USE AND OUTCOMES OF HEMATOPOIETIC STEM CELL TRANSPLANTATION: BRAZILIAN SUMMARY SLIDES – 2024

The development of the Brazilian Registry of Hematopoietic Cell Transplantation in collaboration with the Center for International Blood and Marrow Transplant Research (CIBMTR) allowed for an assessment of the activity and general outcomes of transplants in Brazil. Here, we report an updated activity. Brazilian transplant centers report their data to the CIBMTR, using the FormsNet3 platform. Information returns to Brazilian Cellular Therapy and Bone Marrow Transplant Society (SBTMO) through the Data Back to Centers (DBtC) tool. Data from patients who received an HCT from 2012 to 2023 from Brazilian centers were extracted from CIBMTR. Descriptive analysis was carried out by patient-, disease- and transplant-specific variables and overall survival analysis using Kaplan Meyer. A total of 12,230 patients were eligible for this study (5,573 autologous and 6,657 allogeneic transplants). The number of reporting centers increased from 40 to 44 during the period. The most common HCT indication in Brazil is AML for allogeneic HCT with 152 transplants year and multiple myeloma for autologous HCT with 245 transplants per year. Among allogeneic HCT, in the last 4 years, mismatched related donor was the main source of donors. Regarding the graft source for allogeneic transplants, BM was the most frequent among pediatric transplants, while PBSC was the most used in adults. Infections were the leading cause of death in the first 100 days after all types of transplants. Patients with acute leukemia who underwent HCT with advanced stage disease had lower survival rates compared to those at other stages. Despite the differences in the number of cases and follow-up time, the results in this study were similar to those presented in the United States (US) Summary Slides.

GATA genotype and FY*B(-67T>C) polymorphism as a cheap and reliable tool to evaluate ethnicity in Brazilian patients submitted to autologous transplantation

Abstract Collecting high quality data on race and ethnicity is crucial for clinical research, notably in genetic association studies, to avoid confounding by different ethnic background among patients, a bias referred to as population stratification. In Brazil, to describe race we commonly use the National Institute of Geography and Statistics (IBGE) classification, so-called “self-declared color”, but it is acknowledged that defining ancestry by phenotypic characteristics, especially in countries with highly mixed population like Brazil, can be misleading. We aimed to evaluate the relationship between the GATA FY*B(-67T>C) polymorphism and self-declared race in Brazilian patients undergoing autologous transplantation and verify the feasibility of using this test as a more reliable tool to evaluate ethnicity in this population. Methods: We conducted a study to evaluate the association of candidate-gene polymorphisms and toxicities after autologous stem-cell transplantation (ASCT) in adult patients with lymphoma or myeloma from 2015 to 2021 in two Brazilian transplant centers. All patients with available DNA to study genetic polymorphisms were included. In this analysis we evaluate the association between GATA polymorphism and self-declared color in this cohort. Results: A total of 217 patients were included in this analysis. Median age at transplantation was 56 years (21-79) and 130 patients (59.9%) were male. Most patients were self-declared white (n=175, 80.6%) and the most common genotype was GATA67T/T (wild type/wild type) (n=142, 65.4%). Among the self-declared white patients, 73.1% were genotyped as GATA67T/T and 4.0% as GATA-67C/C, while among the non-white patients 21.4% were genotyped as GATA-67C/C (p<.001). The allele FY*B(-67T>C) frequency was 0.22 in the whole population; it was identified in 26.9% of the self-declared white patients and in 66.6% of the non-white (p<.001). Twelve-month overall survival was 86.6% (95% CI 79.9 - 91.2%), with no difference according to self-declared race (86.8% vs 85.5% for white and non-white patients, respectively, p=0.81) or the presence of the allele FY*B(-67T>C) (85.2% vs 89.9% for non-mutated and mutated patients, respectively, p=0.27). Conclusion: GATA FY*B(-67T>C) polymorphism is associated to self-declared race in Brazilian patients submitted to ASCT. Given the importance of correctly evaluating ancestry in genetic association studies in transplantation, GATA FY*B(-67T>C) polymorphism can be used as a more accurate tool in populations with mixed ethnic/racial background.

Unveiling Trichosporon austroamericanum sp. nov.: A Novel Emerging Opportunistic Basidiomycetous Yeast Species

During an epidemiological survey, a potential novel species within the basidiomycetous yeast genus Trichosporon was observed. The clinical strain was obtained from a urine sample taken from a Brazilian kidney transplant recipient. The strain was molecularly identified using the intergenic spacer (IGS1) ribosomal DNA locus and a subsequent phylogenetic analysis showed that multiple strains that were previously reported by other studies shared an identical IGS1-genotype most closely related to that of Trichosporon inkin. However, none of these studies provided an in-depth characterization of the involved strains to describe it as a new taxon. Here, we present the novel clinically relevant yeast for which we propose the name Trichosporon austroamericanum sp. nov. (holotype CBS H-24937). T. austroamericanum can be distinguished from other siblings in the genus Trichosporon using morphological, physiological, and phylogenetic characters.

(681) - Mitochondrial DNA Quantification of Brazilian Lung Transplant During Ischemia and Reperfusion

(681) - Mitochondrial DNA Quantification of Brazilian Lung Transplant During Ischemia and Reperfusion

Donation and Equitable Access to Organ, Tissue, and Cell Transplants: A Brazilian Perspective on the Strategy and Plan of Action 2019-2030

ObjectiveTo position the Brazilian Transplant System within the context of the 4 Strategic Lines of Action proposed by the Pan-American Health Organization. MethodA specialist analysis was conducted through comparative analyses of the 4 Strategic Lines of Action, objectives, and indicators outlined in the Action Plan, along with the donation and transplantation system in accordance with Brazilian transplantation law. Subsequent to an in-depth review of the document issued by the health authority, a series of meetings involving 8 specialists in organ donation and transplantation were conducted. During these meetings, discussions were carried out with the objective of numerically interpreting each strategy presented in the document, and recommendations constructed. ResultsFour strategies were evaluated and only 2 of them the third (81,3%) and the fourth (90%) do not achieve the indicators to complete the objective related to equitable access to organ, tissue, and cell transplants in Brazil. ConclusionThe recommendations developed carry importance, as they are innovative and contribute to the establishment of priorities when shaping public policies. The report not only highlights indicators that were not satisfactorily met but also provides insights into the recommendations formulated to improve those indicators that have already been achieved and to work toward achieving those that have not yet been realized. Additionally, these recommendations can justify actions and establish priorities for research efforts in the field.

An economic analysis of productivity in organ transplantation in Brazil just before and after the COVID-19 pandemic

We evaluate the productivity of the Brazilian states and the Federal District in transforming potential organ donors into actual donations in the years immediately before and after the COVID-19 pandemic (2019-2022). The Brazilian National Health System (SUS) which is one of the largest public transplant systems in the world, provides full coverage of all costs involved in organ donation, transplants, and post-transplant. We applied Ordinary Least Squares Regression in data from 2019-2022 and the results indicate that there is significant room for improvement in terms of converting potential donors into actual donors. The number of donors with organs transplanted decreased during the pandemic as the productivity of the transplant was affected, although it seems that the structure of the Brazilian transplant system and its technology were not significantly affected permanently.

Excess mortality among kidney transplant recipients: Impact of COVID-19-related deaths during the pandemic.

Because COVID-19 has been associated with high lethality rates among kidney transplant recipients (KTR), but also with a severe disruption and delays in overall healthcare, this study aims to evaluate the excess mortality in the pandemic era among KTR in a high-volume Brazilian transplant center. This study used data from a single center that provides follow-up on all its transplant recipients. The population of interest included all the patients who were transplanted between August 31, 1983 and December 31, 2022 and who were live from January 1, 2014. Using the "AutoRegressive Integrated Moving Average" forecasting algorithm, the expected mortality for the pandemic era (2020-2022) was modeled from the pre-pandemic era (2014-2019). There were 12077 KTRs at risk of dying in the entire observation period. In the pre-pandemic era, there were 21 deaths per 1000 patients at risk. In the pandemic era, there were 1429 observed deaths (rate of 47 deaths per 1000 patients at risk) versus the expected 587 deaths, resulting in an absolute number of 842 excess deaths, or an observed-to-expected ratio of 2.4, or an absolute rate of 26 deaths in excess per 1000 patients at risk. The excess deaths exhibited a temporal pattern mirroring that of the surges in new cases and lethality rates of COVID-19. COVID-19-related deaths drove 94% of excess mortality in the pandemic era. In this large cohort of KTR under centralized follow-up, more than twofold excess mortality was primarily driven by COVID-19-related deaths, highlighting the vulnerability of this population to the most severe presentation of SARS-CoV-2 infection.

A COVID-19 Overview from the Perspective of the Brazilian Kidney Transplantation Program

The Coronavirus disease 2019 (COVID-19) has significantly affected kidney transplantation activities around the world, thus resulting in a substantial decrease in both deceased and living transplants. This study presents a COVID-19 overview from the perspective of the Brazilian kidney transplant program by comparing its differences or similarities with the situations observed in other countries. During the first year of the pandemic, there was a 40% reduction in the number of kidney transplants worldwide. A similar scenario was observed in Brazil, which has the world’s largest public transplantation program. Beyond its effect on transplant activity, COVID-19 has influenced the outcomes of prevalent kidney transplant recipients (KTRs) because the prolonged use of immunosuppressive drugs and comorbidities increase the susceptibility of such patients to severe disease and death. In the pre-vaccination era, almost two-thirds of KTRs required hospitalization, more than 20% required dialysis, and one-third was admitted to the intensive care unit. In the pre-vaccination period in Brazil, 15% and 21% of KTRs died within 28 and 90 days of COVID-19 diagnosis, respectively. Although high vaccination coverage rates have altered the COVID-19 landscape in many populations, persistently low immunogenicity rates following sequential vaccination shots and the absence of targeted treatments for severe cases continue to classify KTRs as highly vulnerable, thus warranting significant concern.

Current use and outcomes of hematopoietic stem cell transplantation: Brazilian summary slides - 2023

The first hematopoietic stem cell transplantation (HSCT) program in Latin America started in 1979 at the federal university hospital in Curitiba, Paraná, Brazil. Over the years, the number of centers performing transplants in our country has increased tremendously, generating the need to know the results of this treatment modality. Understanding the HSCT scenario in Brazil is still challenging, since not all Brazilian centers report data to the Center for International Blood and Marrow Research (CIBMTR). Despite the improvement in the number of reporting centers over the past few years, infrastructure and trained data managers are still lacking. The partnership between the Brazilian Cellular Therapy and Bone Marrow Transplant Society (SBTMO) and the CIBMTR enabled the establishment of the Hematopoietic Stem Cell Transplantation Brazilian Registry (HSCTBR), using the CIBMTR Data Back to Center (DBtC) tool to retrieve Brazilian HSCT data in a standardized and organized way. Since then, it has been possible to gather country-level data on HSCT demographics and transplant outcomes. Between 2012 and 2022, complete information on 9,868 transplants were reported to the CIBMTR from 40 Brazilian transplant centers. The consolidation of the HSCTBR using CIBMTR infrastructure allowed the development and regular update of the Brazilian Summary Slides. Despite the differences in the number of cases and follow-up time, the results in this study were similar to those presented in the United States (US) Summary Slides. In this paper we present the 2023 SBTMO-CIBMTR Summary Slides prepared by the SBTMO data managers (GD-SBTMO).

Current use and outcomes of hematopoietic stem cell transplantation: Brazilian summary slides

The first HSCT program in Latin America started in 1979 at the Federal University Hospital (Curitiba, Paraná). Over the years, the number of centers performing transplants in the country increased, generating the need to know the results of this modality of treatment. Understanding the HSCT scenario in Brazil is still challenging since not all Brazilian centers report data to the Center for International Blood and Marrow Research (CIBMTR). Although it has been improving over the last years, infrastructure and trained data managers are still lacking. The partnership between the Brazilian Cellular Therapy and Bone Marrow Transplant Society (SBTMO) and the CIBMTR, allowed the return of Brazilian data registered in the CIBMTR, through the Data Back to Center (DBtC), in a standardized and organized way. With this database it was possible to know the demographic data and the outcomes of transplants performed in Brazil. Between 2012 and 2021, complete information of 7,982 transplants were reported to the CIBMTR from 31 Brazilian transplant centers. The consolidation of the Hematopoietic Stem Cell Transplantation Brazilian Registry (HSCTBR) using CIBMTR infrastructure, allowed the Brazilian Summary slides development and update. Despite the difference in the number of cases and of follow-up time, the results in this study were similar to those presented in the US Summary Slides.

Impact of the Covid-19 Pandemic on Organ Donation and Transplants at Hospital de Base and in the State of São Paulo, Brazil

Abstract: The Covid-19 pandemic had severe impacts on various sectors of society, especially in the area of medicine. In this area, one segment of activity that was greatly impacted was transplantation, which at first had to be halted in numerous centers, for various reasons. The objective of this article was to analyze, in a comparative way between the years 2019 and 2020, the impact of the Covid-19 pandemic in the numbers of transplantations in a district hospital (DH), a national reference in transplantations, and in the state of São Paulo, as well as in the number of donations from these locations. The method used in this work was the comparative analysis using data obtained from the Brazilian Transplant Registry, the Brazilian Association of Organ Transplantation and the State Transplant System. The following organs were analyzed in the DH and in the state of São Paulo: heart, liver, lung and kidney. Pancreas was analyzed only in the state. Through the analyses, it was observed that in the DH there was a decrease in the numbers of transplantations for all organs analyzed, and in the state of São Paulo, in the numbers of lung and kidney transplantations, maintaining the number of pancreas transplantations and increasing the numbers of heart and liver transplantations. Regarding donors, there was a decrease in the number of potential donors, but an increase in the number of actual donors, due to a decrease in the family refusal rate.

412.3: The Performance of the Kidney Donor Profile Index in Predicting Outcomes for Brazilian Kidney Transplant Recipients of Standard Criteria Donors

412.3: The Performance of the Kidney Donor Profile Index in Predicting Outcomes for Brazilian Kidney Transplant Recipients of Standard Criteria Donors

P14.07: Use of Grafts With Extended Ischemic Time (Above 4 Hours Or More): Analysis of the Experience of the Largest Brazilian Heart Transplant Center, From 2013 to 2022

P14.07: Use of Grafts With Extended Ischemic Time (Above 4 Hours Or More): Analysis of the Experience of the Largest Brazilian Heart Transplant Center, From 2013 to 2022

Hematopoietic stem-cell transplants in Brazil: inequities in the distribution in Brazilian territory, 2001 to 2020

The scope of this article is to describe the distribution of Transplant Centers (TCs) and hematopoietic stem-cell transplants (HSCTs) in the Brazilian territory. It is a descriptive study, which brings together information on the distribution of TCs and the number of procedures performed between 2001 and 2020, based on the following data sources: the Brazilian Cell Therapy and Bone Marrow Transplant Society of (SBTMO); the Brazilian Organ Transplant Association (ABTO); the Hospital Information System of the Unified Health System (SIH/SUS); and the Ministry of Health (MS). A total of 86 TCs were identified, predominantly in the Southeastern region of the country (64%). There are no TCs in the Northern region. Throughout the period, there were more than 30,000 procedures, concentrated in the Southeastern and Southern regions. The allogeneic type of HSCT was prevalent. Differences were found between the numbers of transplants performed depending on the source consulted. Despite the increase in the number of procedures during the period studied, both the distribution of TCs and the number of HSCTs were concentrated in more developed regions. This heterogeneity may have led to inequities in the access of the population to treatment.

Is Severity Score Associated With Indication for Hematopoietic Stem Cell Transplantation in Individuals With Sickle Cell Anemia?

Manifestations 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-III 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.

Incidence and Impact of COVID-19 Cases in Brazilian Liver Transplant Recipients: An Academic, Single-center Experience

BackgroundCurrent literature reports diverge on the impact of COVID-19 in liver transplant (LT) recipients. Literature findings often report conflicting results, relying on small sample sizes, limited ethnic variability, and nonstandardized methodologies. Notably, there are no studies on this topic regarding Latin American populations. This study seeks to report the impact of COVID-19, disease characteristics, and progression in LT recipients in a Latin American academic center environment.MethodsThe study design was a historic cohort, including adult LT recipient patients with suspected or confirmed COVID-19 who sought care between December 2019 to October 2021. The primary end point was defined as COVID-19–related death. Demographic, clinical, and laboratory data was also collected.ResultsTwenty-seven patients were included, representing a 3.5% incidence within 752 patients in the follow-up. The mean age and years from transplantation were 54 (SD ± 11) and 6.3 years (SD ± 5.4), respectively. Most patients were white (23 - 85.2%) and male (21 - 25.2%). The hospitalization rate was 55.6%, and 5 patients (18.5%), all of whom subsequently died, were admitted to the intensive care unit. Neither the presence of comorbidities nor advanced age were related to lethality. Patients with immunosuppression modifications (P = 0.039) or isolated tacrolimus suspension (P = 0.006) were associated with increased mortality.ConclusionsThis study described COVID-19 infections in LT recipients in Latin American populations. This group was not affected by common factors associated with higher lethality, and displayed a tendency toward lower hospitalization rates. Our study concurred with previously reported evidence of a protective association of tacrolimus maintenance during treatment in LT recipients affected by COVID-19.

Temporal Reduction in COVID-19-Associated Fatality Among Kidney Transplant Recipients: The Brazilian COVID-19 Registry Cohort Study.

Data from the general population suggest that fatality rates declined during the course of the pandemic. This analysis, using data extracted from the Brazilian Kidney Transplant COVID-19 Registry, seeks to determine fatality rates over time since the index case on March 3rd, 2020. Data from hospitalized patients with RT-PCR positive SARS-CoV-2 infection from March to August 2020 (35 sites, 878 patients) were compared using trend tests according to quartiles (Q1: <72 days; Q2: 72–104 days; Q3: 105–140 days; Q4: >140 days after the index case). The 28-day fatality decreased from 29.5% (Q1) to 18.8% (Q4) (p for-trend = 0.004). In multivariable analysis, patients diagnosed in Q4 showed a 35% reduced risk of death. The trend of reducing fatality was associated with a lower number of comorbidities (20.7–10.6%, p for-trend = 0.002), younger age (55–53 years, p for-trend = 0.062), and better baseline renal function (43.6–47.7 ml/min/1.73 m2, p for-trend = 0.060), and were confirmed by multivariable analysis. The proportion of patients presenting dyspnea (p for-trend = 0.001) and hypoxemia (p for-trend < 0.001) at diagnosis, and requiring intensive care was also found reduced (p for-trend = 0.038). Despite possible confounding variables and time-dependent sampling differences, we conclude that COVID-19-associated fatality decreased over time. Differences in demographics, clinical presentation, and treatment options might be involved.

Development and validation of a simple web-based tool for early prediction of COVID-19-associated death in kidney transplant recipients

This analysis, using data from the Brazilian kidney transplant (KT) COVID‐19 study, seeks to develop a prediction score to assist in COVID‐19 risk stratification in KT recipients. In this study, 1379 patients (35 sites) were enrolled, and a machine learning approach was used to fit models in a derivation cohort. A reduced Elastic Net model was selected, and the accuracy to predict the 28‐day fatality after the COVID‐19 diagnosis, assessed by the area under the ROC curve (AUC‐ROC), was confirmed in a validation cohort. The better calibration values were used to build the applicable ImAgeS score. The 28‐day fatality rate was 17% (n = 235), which was associated with increasing age, hypertension and cardiovascular disease, higher body mass index, dyspnea, and use of mycophenolate acid or azathioprine. Higher kidney graft function, longer time of symptoms until COVID‐19 diagnosis, presence of anosmia or coryza, and use of mTOR inhibitor were associated with reduced risk of death. The coefficients of the best model were used to build the predictive score, which achieved an AUC‐ROC of 0.767 (95% CI 0.698–0.834) in the validation cohort. In conclusion, the easily applicable predictive model could assist health care practitioners in identifying non‐hospitalized kidney transplant patients that may require more intensive monitoring. Trial registration: ClinicalTrials.gov NCT04494776.