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.

Prevalence and Risk Factors for Human T-Cell Lymphotropic Virus (HTLV) in Blood Donors in Brazil-A 10-Year Study (2007-2016).

It is unknown whether HTLV-1/2 prevalence has been stable or changing with time in Brazil. We present a 10-year (2007-2016) analysis of HTLV-1/2 infection in first-time blood donors from four blood banks in Brazil. The Brazilian blood centers participating in this multicenter Recipient Epidemiology and Donor Evaluation Study (REDS) are located in Recife in the Northeast and in São Paulo, Rio de Janeiro and Belo Horizonte located in the Southeast of the country. A previous REDS study using the same database from 2007 to 2009 showed that the prevalence per 100,000 donors was 222 in Recife, 83 in Belo Horizonte and 101 in São Paulo. From 2007 to 2016, HTLV-1/2 prevalence was calculated by year, blood center and birth cohort. Covariates included age, gender, schooling, self-reported skin color and type of donation. From 1,092,174 first-blood donations, in the general analysis, HTLV-1/2 infection predominated in females, donors over 50 years of age, black skin color and less educated. The average prevalence was 228 per 100,000 donors in Recife, 222 in Rio de Janeiro, 104 in Belo Horizonte and 103 in São Paulo. In the 10-year analysis, HTLV-1/2 prevalence was stable, but a trend was observed toward an increase in HTLV-1/2 infection among younger people (p < 0.001), males (p = 0.049), those with white skin color (p < 0.001), and higher education (p = 0.014). Therefore, this 10-year surveillance of the infection showed stable HTLV-1/2 prevalence overall but a trend toward increased prevalence among the younger and more educated donors despite Brazilian policies to control sexually transmitted infections being in place for more than 10 years.

Association of HIV infection with clinical and laboratory characteristics of sickle cell disease.

BACKGROUND: Sickle cell disease (SCD) is a multisystem disorder characterized by a wide spectrum of clinical manifestations and severity. Studies investigating potential effects of co-morbid human immunodeficiency virus (HIV) and SCD have produced conflicting results, and additional investigations are needed to elucidate whether the interaction between the two disease states might impact both HIV and SCD clinical outcomes. The association of HIV infection with clinical and laboratory characteristics of patients with SCD was assessed. METHODS: This nested case-control study included individuals with SCD with HIV treated at six Brazilian SCD centers. Clinical and laboratory data were abstracted from medical records. HIV positive participants were compared to age, gender, center, and SCD genotype matched HIV negative participants (ratio 1:4). Individual clinical outcomes as well as a composite outcome of any SCD complication and a composite outcome of any HIV-related complication were compared between the two groups. RESULTS: Fifteen HIV positive participants were included, 12 (80%) alive and 3 (20%) deceased. Most of the HIV positive patients had HbSS (60%; n = 9), 53% (n = 8) were female, and mean age was 30 ± 13 years. The frequency of individual SCD complications of acute chest syndrome/pneumonia, sepsis/bacteremia, pyelonephritis, ischemic stroke, hemorrhagic stroke, abnormal transcranial Doppler (TCD), and pulmonary hypertension was higher in HIV positive participants when compared to HIV negative, although analyzed individually none were statistically significant. HIV positive participants had significantly higher risk of any SCD complication and of a composite HIV-related complication compared to the HIV negative group (HR = 4.6; 95%CI 1.1-19.6; P = 0.04 and HR = 7.7; 95%CI 1.5-40.2; P = 0.02, respectively). There was a non-significant trend towards higher risk of any infections in participants with HIV positive (HR = 3.5; 95%CI 0.92-13.4; P = 0.07). Laboratory parameters levels were not significantly different in individuals with and without HIV. CONCLUSIONS: In summary, our study in SCD patients shows that those with HIV have an increased risk of any SCD complication and HIV-related complications, as well as a suggestive but not significantly increased risk of infections.

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.

BACKGROUND: 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: Infection markers 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.

Blood Donor Test-Seeking Motivation and Prior HIV Testing Experiences in São Paulo, Brazil.

HIV test-seeking behavior among blood donors has been observed worldwide and may pose a threat to the safety of the blood supply. We evaluated current test-seeking motivations and prior alternative HIV testing experiences among blood donors in São Paulo, Brazil. All candidate or potential blood donors were consecutively approached and recruited to participate in the study upon presentation at Fundação Pró-Sangue Hemocentro, the largest blood bank in Brazil. Participants were recruited between August 2012 and May 2013 after they were screened for donor eligibility. Questionnaires were administered through audio computer-assisted self-interview. Among 11,867 donors, 38 % previously tested for HIV apart from blood donation, of whom 47.7 % tested at public facilities and 2.7 % acknowledged getting tested for HIV as the primary reason for donating. Dissatisfaction with prior alternative testing experience was reported by 2.5 % of donors. Current test-seeking motivation was associated with dissatisfaction with prior alternative testing experience and testing at a public alternative facility. The most common reasons for dissatisfaction were too long of a wait to get tested and for results, counseling was too long, lack of privacy, and low confidence in the equipment and accuracy of the test. Lack of awareness about the availability of free and confidential public HIV testing services as well as dissatisfaction with past HIV testing and counseling experiences motivate some individuals to test at blood banks. Test-seeking behavior among blood donors may be best addressed by improving alternative testing programs, particularly with respect to time delays, privacy and perceptions about test accuracy. Educational campaigns on safe blood donation and HIV testing for diagnosis, risk counseling and referral to care are also needed for the general public and for health care providers.

Does offering human immunodeficiency virus testing at the time of blood donation reduce transfusion transmission risk and increase disclosure counseling? Results of a randomized controlled trial, São Paulo, Brazil.

BACKGROUND: In a randomized controlled trial (RCT) in a blood bank in São Paulo, we tested the hypotheses that offering client-centered human immunodeficiency virus (HIV) counseling and testing to blood donors would: 1) reduce the risk of HIV contamination in the blood supply by diverting higher-risk, test-seeking donors away from donation and 2) increase return for results and referrals to care. STUDY DESIGN AND METHODS: We randomly selected weeks between August 2012 and May 2013 when donors were offered HIV counseling and testing (n = 6298), leaving usual procedure weeks as control (n = 5569). RESULTS: Few candidate donors chose HIV testing (n = 81, 1.3%). There was no significant difference in herpes simplex virus Type 2 (HSV-2) prevalence (a marker of sexual risk) among donors during intervention weeks compared to control (10.4% vs. 11.1%, p = 0.245). No donor choosing testing was HIV infected, and there was no difference in HSV-2 prevalence between testers and donors (9.9% vs. 10.4%, p = 0.887). Returning for positive results did not differ between testers and donors (three of three vs. 58 of 80, p = 0.386). A higher proportion of donors acknowledged that HIV testing was a strong motivation to donate during intervention weeks compared to control (2.6% vs. 2.0%, p = 0.032). CONCLUSION: The evidence of our RCT is that offering HIV counseling and testing at the time of donation would not change the risk of contamination in the blood supply, nor improve results disclosure and referral to care.

Contribution of the Retrovirus Epidemiology Donor Study (REDS) to research on blood transfusion safety in Brazil.

The Retrovirus Epidemiology Donor Study (REDS) program was established in the United States in 1989 with the purpose of increasing blood transfusion safety in the context of the HIV/AIDS and human T-lymphotropic virus epidemics. REDS and its successor, REDS-II were at first conducted in the US, then expanded in 2006 to include international partnerships with Brazil and China. In 2011, a third wave of REDS renamed the Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) was launched. This seven-year research program focuses on both blood banking and transfusion medicine research in the United States of America, Brazil, China, and South Africa. The main goal of the international programs is to reduce and prevent the transmission of HIV/AIDS and other known and emerging infectious agents through transfusion, and to address research questions aimed at understanding global issues related to the availability of safe blood. This article describes the contribution of REDS-II to transfusion safety in Brazil. Articles published from 2010 to 2013 are summarized, including database analyses to characterize blood donors, deferral rates, and prevalence, incidence and residual risk of the main blood-borne infections. Specific studies were developed to understand donor motivation, the impact of the deferral questions, risk factors and molecular surveillance among HIV-positive donors, and the natural history of Chagas disease. The purpose of this review is to disseminate the acquired knowledge and briefly summarize the findings of the REDS-II studies conducted in Brazil as well as to introduce the scope of the REDS-III program that is now in progress and will continue through 2018.

Contribution of the Retrovirus Epidemiology Donor Study (REDS) to research on blood transfusion safety in Brazil

The Retrovirus Epidemiology Donor Study (REDS) program was established in the United States in 1989 with the purpose of increasing blood transfusion safety in the context of the HIV/AIDS and human T-lymphotropic virus epidemics. REDS and its successor, REDS-II were at first conducted in the US, then expanded in 2006 to include international partnerships with Brazil and China. In 2011, a third wave of REDS renamed the Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) was launched. This seven-year research program focuses on both blood banking and transfusion medicine research in the United States of America, Brazil, China, and South Africa. The main goal of the international programs is to reduce and prevent the transmission of HIV/AIDS and other known and emerging infectious agents through transfusion, and to address research questions aimed at understanding global issues related to the availability of safe blood. This article describes the contribution of REDS-II to transfusion safety in Brazil. Articles published from 2010 to 2013 are summarized, including database analyses to characterize blood donors, deferral rates, and prevalence, incidence and residual risk of the main blood-borne infections. Specific studies were developed to understand donor motivation, the impact of the deferral questions, risk factors and molecular surveillance among HIV-positive donors, and the natural history of Chagas disease. The purpose of this review is to disseminate the acquired knowledge and briefly summarize the findings of the REDS-II studies conducted in Brazil as well as to introduce the scope of the REDS-III program that is now in progress and will continue through 2018.

Non-neoplastic bulky mediastinal mass presentation in an adolescent patient: a case report.

INTRODUCTION: Mediastinal masses in pediatric patients are very heterogeneous in origin and etiology. In the first decade of life, 70% of the mediastinal masses are benign whereas malignant tumors are more frequent in the second decade of life. Among the mediastinal masses, lymph nodes are the most common involved structures and could be enlarged due to a lymphoma, leukemia, metastatic disease, or due to infectious diseases as sarcoidosis, tuberculosis and others. CASE PRESENTATION: We report a case of a 13-year-old Caucasian girl who came to the emergency room with a history of intermittent fever, weight loss and night sweating for at least 1 month. A radiologic image work-up presented an anterior and posterior mediastinal mass. The 18F-fluorodeoxyglucose positron emission tomography presented a high maximum standard uptake value, which directed our decision for mediastinal biopsy for diagnostic elucidation. Histologic examination described the mass as granulomatous tuberculosis. The patient was treated with anti-tuberculosis therapy and developed a full clinical recovery. CONCLUSIONS: The present case report demonstrates that a bulky mediastinal lymphadenopathy detected on 18F-fluorodeoxyglucose positron emission tomography is not always a malignant lesion, and in countries where tuberculosis is endemic, this etiology should not be forgotten during clinical investigations. There is a need for more accurate cut-off values for this technology; meanwhile, the further investigation of patients with bulky mediastinal masses with procedures such as the open biopsy is indispensable.

Undisclosed human immunodeficiency virus risk factors identified through a computer-based questionnaire program among blood donors in Brazil.

BACKGROUND: Human immunodeficiency virus (HIV) risk factor screening among blood donors remains a cornerstone for the safety of blood supply and is dependent on prospective donor self-disclosure and an attentive predonation interview. Audio computer-assisted structured interview (ACASI) has been shown to increase self-reporting of risk behaviors. STUDY DESIGN AND METHODS: This cross-sectional study was conducted between January 2009 and March 2011 at four Brazilian blood centers to identify the population of HIV-negative eligible blood donors that answered face-to-face interviews without disclosing risks, but subsequently disclosed deferrable risk factors by ACASI. Compared to the donor interview, the ACASI contained expanded content on demographics, sexual behavior, and other HIV risk factors questions. RESULTS: A total of 901 HIV-negative blood donors were interviewed. On the ACASI, 13% of donors (n = 120) declared a risk factor that would have resulted in deferral that was not disclosed during the face-to-face assessment. The main risk factors identified were recent unprotected sex with an unknown or irregular partner (49 donors), sex with a person with exposure to blood or fluids (26 donors), multiple sexual partners (19 donors), and male-male sexual behavior (10 donors). Independent factors associated with the disclosure of any risk factor for HIV were age (≥40 years vs. 18-25 years; adjusted odds ratio [AOR], 0.45; 95% confidence interval [CI], 0.23-0.88) and blood center (Hemope vs. Hemominas; AOR, 2.51; 95% CI, 1.42-4.44). CONCLUSION: ACASI elicited increased disclosure of HIV risk factors among blood donors. ACASI may be a valuable modality of interview to be introduced in Brazilian blood banks.

The impact of policies to restrict the use of plasma containing products and apheresis platelets from female donors to mitigate transfusion related acute lung injury (TRALI) in Brazil.

BACKGROUND AND OBJECTIVES: Although the incidence of TRALI is unknown in Brazil, some blood centers have adopted strategies to prevent TRALI. We evaluated the impact of three policies to mitigate TRALI on the supply of blood products: to divert the production of whole blood-derived plasma from female donors; to defer all female donors from apheresis platelet collections, and to defer only multiparous female donors from apheresis platelet collections. MATERIALS AND METHODS: Data from allogeneic whole blood and apheresis platelet donations from April 2008 to December 2009 were collected in three Brazilian blood centers and the impact of the aforementioned strategies was evaluated. RESULTS: Of 544,814 allogeneic blood donations, 30.8% of whole blood plasma and 24.1% of apheresis platelet donations would be reduced if only male donor plasma was issued for transfusion and all female donors were deferred from apheresis donation, respectively. If only multiparous donors were deferred from apheresis donation, there would be a 5% decrease of all apheresis platelet collections. CONCLUSION: Restricting the use of whole blood derived plasma to male-only donors and deferring all female apheresis platelet donors would impact two out of three Brazilian blood centers. A deferral policy on multiparous apheresis platelet donors may be acceptable as a temporary measure, but may cause more stress on a system that is already working at its limit.

Prevalence of serologic markers for hepatitis B and C viruses in Brazilian blood donors and incidence and residual risk of transfusion transmission of hepatitis C virus.

BACKGROUND: We evaluate the current prevalence of serologic markers for hepatitis B virus (HBV) and hepatitis C virus (HCV) in blood donors and estimated HCV incidence and residual transfusion-transmitted risk at three large Brazilian blood centers. STUDY DESIGN AND METHODS: Data on whole blood and platelet donations were collected from January through December 2007, analyzed by center; donor type; age; sex; donation status; and serologic results for hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen (anti-HBc), and anti-HCV. HBV and HCV prevalence rates were calculated for all first-time donations. HCV incidence was derived including interdonation intervals that preceded first repeat donations given during the study, and HCV residual risk was estimated for transfusions derived from repeat donors. RESULTS: There were 307,354 donations in 2007. Overall prevalence of concordant HBsAg and anti-HBc reactivity was 289 per 100,000 donations and of anti-HCV confirmed reactivity 191 per 100,000 donations. There were significant associations between older age and hepatitis markers, especially for HCV. HCV incidence was 3.11 (95% confidence interval, 0.77-7.03) per 100,000 person-years, and residual risk of HCV window-phase infections was estimated at 5.0 per million units transfused. CONCLUSION: Improvement in donor selection, socioeconomic conditions, and preventive measures, implemented over time, may have helped to decrease prevalence of HBV and HCV, relative to previous reports. Incidence and residual risk of HCV are also diminishing. Ongoing monitoring of HBV and HCV markers among Brazilian blood donors should help guide improved recruitment procedures, donor selection, laboratory screening, and counseling strategies.

Ovarian failure in SLE patients using pulse cyclophosphamide: comparison of different regimes.

The objective of this study was to determine the frequency and risk factors of early ovarian failure in systemic lupus erythematosus (SLE) women treated with cyclophosphamide (CY). We further tried to determine if there was a reduction of ovarian failure in recent years, due to reduction in the CY dose. We reviewed the charts of all women below 40 years of age who received intravenous CY pulse therapy. In order to be included, the patients must have finished CY treatment before completing 40 years. Patients were divided into two groups: Group A (57 patients), patients who were treated with 0.75 mg/body surface; Group B (50 patients), patients treated with 0.5 mg/body surface. Fifty patients with similar age distribution who never received CY were selected from the database as a control group (Group C). The Chi-square test was applied to compare the categorical variables of the groups and whenever needed, the Fisher's Exact test was used. We observed similar age distribution and disease duration at disease onset between groups. Also, no differences regarding the age at menarche, total prednisone dose, and SLICC-ACR/DI scores were observed at disease onset between the three groups. In group A, ten (17.5%) patients refereed sustained amenorrhea, independently associated with treatment duration (P = 0.001), total intravenous cyclophosphamide (IV-CF) dose (P = 0.02), older age at disease onset (P = 0.04). Seven (12.3%) patients referred transient amenorrhea. Transient amenorrhea was related to CY treatment duration (P = 0.017). In group B, no patient reported sustained amenorrhea and 10 of 50 (20%) patients referred transient amenorrhea, related to CY treatment duration (P = 0.017). The most important risk factors for menstrual abnormalities were duration of treatment and cumulative dose of CY. Lower CY dose reduced the number of premature ovarian failures significantly in this cohort.