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High-dose therapy followed by autologous hematopoietic cell transplant (AHCT) remains a viable consolidation strategy for a subset of patients with relapsed or refractory (R/R) lymphomas. BEAM (carmustine, etoposide, cytarabine, and melphalan) is widely recognized as the predominant conditioning regimen due to its satisfactory efficacy and tolerability. Nevertheless, shortages of carmustine and melphalan have compelled clinicians to explore alternative conditioning regimens. The aim of this study was to compare the toxicity and transplant outcomes following BEAM, CBV (carmustine, etoposide, cyclophosphamide), BuMel (busulfan, melphalan), and BendaEAM (bendamustine, etoposide, cytarabine, melphalan). We retrospectively analyzed data from 213 patients (CBV 65, BuMel 42, BEAM 68, BendaEAM 38) with R/R lymphomas undergoing AHCT between 2014 and 2020. Multivariate models were employed to evaluate toxicity and transplant outcomes based on conditioning type. Among grade III to IV toxicities, oral mucositis was more frequently observed with BuMel (45%) and BendaEAM (24%) compared to BEAM (15%) and CVB (6%, P ≤ .001). Diarrhea was more common with BendaEAM (42%) and less frequent with BuMel (7%, P = .01). Acute kidney injury was only found after BendaEAM (11%). Febrile neutropenia and infectious complications were more frequent following BendaEAM. Frequencies of other treatment-related toxicities did not significantly differ according to conditioning type. BendaEAM (odds ratio [OR] 3.07, P = .014) and BuMel (OR 4.27, P = .002) were independently associated with higher grade III to IV toxicity up to D+100. However, there were no significant differences in relapse/progression, nonrelapse mortality, progression-free survival, or overall survival among the four regimens. BuMel and BendaEAM were associated with a higher rate of grade III to IV toxicity. Carmustine-based regimens appeared to be less toxic and safer; however, there were no significant differences in transplant outcomes. The utilization of alternative preparative regimens due to drug shortages may potentially lead to increased toxicity after AHCT for lymphoma.
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Carmustina , Citarabina , Trasplante de Células Madre Hematopoyéticas , Linfoma , Melfalán , Acondicionamiento Pretrasplante , Trasplante Autólogo , Humanos , Acondicionamiento Pretrasplante/métodos , Masculino , Femenino , Persona de Mediana Edad , Linfoma/tratamiento farmacológico , Linfoma/terapia , Adulto , Carmustina/uso terapéutico , Estudios Retrospectivos , Citarabina/uso terapéutico , Melfalán/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Anciano , Etopósido/uso terapéutico , Busulfano/uso terapéutico , Resultado del Tratamiento , Ciclofosfamida/uso terapéuticoRESUMEN
The present text presents partial results of the research "Young people with disability due to gunshot wounds: an exploratory study from the Memorialistic Narratives", which aimed to problematize the effects of violence and criminality in the juvenile sphere by investigating, beyond the increase in mortality and incarceration rates, the transformation of these young people into people with disabilities, specifically, people in wheelchairs. To achieve this goal, we used as a method the Memorialistic Narratives and worked on the categories of exclusion, violence and a body marked by trauma. We will reflect on the case of Guilherme, a poor, marginalized young man with a disability and a wheelchair user due to a gunshot wound. The choice for his case relates to the different forms that violence can assume, influencing lives and leaving marks, besides, we believe that his life story can contribute to qualifying psychology's look at young people in contexts of violence.
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INTRODUCTION: Autologous hematopoietic stem cell transplantation (ASCT) is the long-term consolidation treatment for various hematological malignancies. The collection of hematopoietic stem cell yield is critical to successful ASCTs, but not always achieved due to hematopoietic stem cell mobilization failure (HSCMF). Details regarding the cell collection and outcomes of those who fail mobilization are still lacking. Therefore, this study aimed to yield data on clinical outcomes and cellular products after HSCMF. METHODS: Retrospective, unicentric study assessing clinical outcomes and characteristics of collected progenitor cells. The data were collected from patient databases. The results were reported in median, rates and percentages and absolute values. Patients older than 18 years of age at the time of mobilization and HSCMF were included. RESULTS: Five hundred ninety-nine patients underwent mobilization protocols. Thirty-five (5.8%) of them failed in the mobilization and fourteen (40%) died. Median time to death was eight months. Disease progression and infection were responsible for all deaths. Median relapse-free survival was 6.5 months (20 patients, 57%). Seven (20%) survivors were receiving salvage therapy and five (14%) were being followed clinically. Six (20.6%) participants underwent collection by apheresis, with insufficient cell collection. The median quantity of peripheral CD34+ cells in those patients was 10.5/mm3. The median CD34+ quantity collected was 0.86 × 106 CD34+ cells/kg. CONCLUSIONS: The mobilization failure was associated with limited survival. Nonetheless, collected products offered perspectives for ex vivo expansion. Further studies should investigate the feasibility of expanding collected CD34+ cells to use as grafts for ASCT.
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The aim of this study was to evaluate the prevalence of latent Mycobacterium tuberculosis infection in hematopoietic stem cell transplantation candidates, using tuberculin skin test and QuantiFERON-TB Gold-Plus, in a high-burden tuberculosis country. Adult candidates for hematopoietic stem cell transplantation performed both tests before and those submitted to transplantation were followed up for 12 months. The prevalence of latent Mycobacterium tuberculosis infection was 17.1% and a moderate agreement between QuantiFERON-TB Gold-Plus and tuberculin skin test was observed in this population. Previous tuberculosis exposure was a risk factor for latent Mycobacterium tuberculosis infection. No cases of tuberculosis were diagnosed during follow-up period.
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Trasplante de Células Madre Hematopoyéticas , Tuberculosis Latente , Mycobacterium tuberculosis , Tuberculosis , Adulto , Humanos , Ensayos de Liberación de Interferón gamma , Prueba de Tuberculina , Prevalencia , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/epidemiología , Tuberculosis Latente/microbiología , Tuberculosis/diagnóstico , Tuberculosis/epidemiología , Trasplante de Células Madre Hematopoyéticas/efectos adversosRESUMEN
BACKGROUND: Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that causes severe diseases, such as aggressive cancer or progressive neurological disease. HTLV-1 affects mainly people in areas with low human development index and can be transmitted from mother to child, primarily through breastfeeding. Refraining from breastfeeding is an effective intervention to reduce the risk of infection in infants. However, HTLV-1 antenatal screening is not offered globally. According to WHO, the scarcity of cost-effectiveness studies is considered one of the major barriers to the implementation of policies to prevent HTLV-1 infection. Therefore, this study aimed to assess the cost-effectiveness of antenatal screening and postnatal interventions to prevent HTLV-1 mother-to-child transmission in Brazil and to develop an open-access, editable, mathematical model that can be used by other countries and regions to assess different scenarios. METHODS: In this cost-utility analysis, we constructed a decision tree and a Markov model to assess the cost-effectiveness of HTLV-1 antenatal screening and postnatal interventions (ie, avoidance of breastfeeding, by suppression of lactation with cabergoline, and provision of formula feed) to reduce transmission. For our model, we used data from Brazil and we took the perspective of the public health-care system to estimate costs. FINDINGS: The implementation of both screening and interventions would result in the prevention of 1039 infections in infants every year in Brazil with an incremental cost-effectiveness ratio (ICER) of US$11â415 per quality-adjusted life-year (QALY). 88% of all probabilistic sensitivity analysis simulations had ICER values lower than the Brazilian cost-effectiveness threshold ($18â107·74 per QALY). HTLV-1 prevalence in pregnant women, the risk of HTLV-1 transmission when breastfeeding lasts for 6 months or more, and the cost of screening tests were the variables with the largest effect on ICER. INTERPRETATION: HTLV-1 antenatal screening is cost-effective in Brazil. An open-access model was developed, and this tool could be used to assess the cost-effectiveness of such policy globally, favouring the implementation of interventions to prevent HTLV-1 mother-to-child transmission worldwide. FUNDING: None. TRANSLATIONS: For the Portuguese and Spanish translations of the abstract see Supplementary Materials section.
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Virus Linfotrópico T Tipo 1 Humano , Lactante , Femenino , Humanos , Embarazo , Brasil/epidemiología , Acceso a la Información , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Diagnóstico Prenatal , Análisis Costo-Beneficio , Linfocitos TRESUMEN
In single unrelated cord blood transplantation (UCBT), an increasing number of HLA allele mismatches (MM) has been associated with inferior overall survival (OS) and attributed to higher transplant-related mortality (TRM). Previous studies on the role of allele-level HLA matching after double UCBT (dUCBT) showed conflicting results. In this study, we report the impact of allele-level HLA matching on the outcomes of a large dUCBT cohort. We included 963 adults with hematologic malignancies, with available allele-level HLA matching at HLA-A, -B, -C, and -DRB1, receiving dUCBT between 2006 to 2019. Assignment of donor-recipient HLA match was performed considering the unit with the highest disparity with the recipient. Three hundred ninety-two patients received dUCBT with 0 to 3 MM and 571 with ≥4 allele MM. For recipients of dUCBT with 0 to 3 MM, day-100 and 4-year TRM were 10% and 23%, respectively, compared with 16% and 36% for those with ≥4 MM. A higher degree of allele MM was also associated with the worse neutrophil recovery and lower incidence of relapse; no significant effect on graft-versus-host disease was observed. Patients receiving units with 0 to 3 MM had a 4-year OS of 54% compared with 43% for those receiving units with ≥4 MM. The inferior OS associated with higher HLA disparity was only partially mitigated by increased total nucleated cell doses. Our results confirm that allele-level HLA typing is a significant factor for OS after dUCBT, and units with ≥4 MM (≤4/8 HLA-matched) should be avoided if possible.
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Trasplante de Células Madre de Sangre del Cordón Umbilical , Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Humanos , Adulto , Alelos , Trasplante de Células Madre de Sangre del Cordón Umbilical/efectos adversos , Trasplante de Células Madre de Sangre del Cordón Umbilical/métodos , Recurrencia Local de Neoplasia , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/terapiaRESUMEN
Failure-free survival (FFS), defined as the absence of new systemic treatment, recurrence of original malignancy and mortality not associated with recurrence after allogeneic hematopoietic stem cell transplantation (HCT), is a robust clinical measure to interpret results of initial systemic treatment of chronic graft-versus-host disease (cGVHD). We evaluate FFS after initial treatment of cGVHD in a mixed-race cohort from a resource-constrained country. This retrospective study included 354 consecutive patients after their first HCT between January 2014 and August 2020, who received initial systemic treatment for moderate or severe cGVHD at 13 Brazilian centers. Cox regression models were used to identify risk factors for treatment failure. The overall median follow-up among survivors was 28 months (range 1-71) after initial treatment. FFS was 89% at 6 months, 71% at 1 year and 52% at 2 years. New systemic treatment was the major cause of failure. In multivariable models, prior grades II-IV acute GVHD, a National Institutes of Health severity score of 3 in liver, gastrointestinal tract or lung involvement, and onset of initial treatment of cGVHD within 12 months after transplantation were all associated with an increased risk of treatment failure. Our results could serve as a benchmark for the design of future clinical trials evaluating initial treatment of cGVHD in resource-constrained locations.
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Síndrome de Bronquiolitis Obliterante , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Estados Unidos , Humanos , Brasil/epidemiología , Estudios Retrospectivos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Enfermedad Injerto contra Huésped/tratamiento farmacológicoRESUMEN
Background Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that causes severe diseases, such as aggressive cancer or progressive neurological disease. HTLV-1 affects mainly people in areas with low human development index and can be transmitted from mother to child, primarily through breastfeeding. Refraining from breastfeeding is an effective intervention to reduce the risk of infection in infants. However, HTLV-1 antenatal screening is not offered globally. According to WHO, the scarcity of cost-effectiveness studies is considered one of the major barriers to the implementation of policies to prevent HTLV-1 infection. Therefore, this study aimed to assess the cost-effectiveness of antenatal screening and postnatal interventions to prevent HTLV-1 mother-to-child transmission in Brazil and to develop an open-access, editable, mathematical model that can be used by other countries and regions to assess different scenarios. Methods In this cost-utility analysis, we constructed a decision tree and a Markov model to assess the cost-effectiveness of HTLV-1 antenatal screening and postnatal interventions (ie, avoidance of breastfeeding, by suppression of lactation with cabergoline, and provision of formula feed) to reduce transmission. For our model, we used data from Brazil and we took the perspective of the public health-care system to estimate costs. Findings The implementation of both screening and interventions would result in the prevention of 1039 infections in infants every year in Brazil with an incremental cost-effectiveness ratio (ICER) of US$11415 per quality-adjusted lifeyear (QALY). 88% of all probabilistic sensitivity analysis simulations had ICER values lower than the Brazilian costeffectiveness threshold ($18 107·74 per QALY). HTLV-1 prevalence in pregnant women, the risk of HTLV-1 transmission when breastfeeding lasts for 6 months or more, and the cost of screening tests were the variables with the largest effect on ICER. Interpretation HTLV-1 antenatal screening is cost-effective in Brazil. An open-access model was developed, and this tool could be used to assess the cost-effectiveness of such policy globally, favouring the implementation of interventions to prevent HTLV-1 mother-to-child transmission worldwide. (AU)
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Diagnóstico Prenatal , Brasil , Linfocitos T , Virus Linfotrópico T Tipo 1 Humano , Análisis Costo-BeneficioRESUMEN
Multidrug-resistant pathogens have emerged worldwide. We have driven the hypothesis that the non-use of fluoroquinolone prophylaxis during neutropenia could reduce antibiotic resistance in Gram-negative bacteria that cause bloodstream infections (BSIs) in hematopoietic stem cell transplantation (HSCT) patients and that this change in resistance pattern could lead to an impact on BSI mortality. This is a quasi-experimental study comparing BSI incidence, resistance patterns of bacteria that cause BSI, and BSI mortality when levofloxacin prophylaxis was routine for neutropenic HSCT patients (2016-2018) to when fluoroquinolone prophylaxis was discontinued in our center (2019). Bivariate comparisons and multivariate logistic regression models were used for analyses. A total of 310 HSCTs (66 (21%) allogeneic and 244 (79%) autologous) were performed during the study period. Sixty (19%) patients had BSIs, 30 in each evaluated period. The discontinuation of levofloxacin prophylaxis was associated with an increase in BSI incidence and a decrease in the resistance rates of causative BSI bacteria and in BSI 30-day mortality. The increase in the rate of resistant bacteria causing BSI and in BSI mortality might outweigh the benefits of a decrease in BSI incidence caused by fluoroquinolone prophylaxis in neutropenic HSCT patients. We suggest that the routine use of fluoroquinolone in this context be revisited.
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Trasplante de Células Madre Hematopoyéticas , Telemedicina , Humanos , Brasil , Hospitales PúblicosRESUMEN
In the COVID-19 scenario, patients undergoing hematopoietic stem cell transplantation (HSCT) infected with SARS-CoV-2 may have an increased risk of death. Through a national multicenter study, we aimed to describe the impact of COVID-19 on the survival of HSCT recipients in Brazil. Eighty-six patients with a confirmed diagnosis of SARS-CoV-2 (92% by RT-PCR) were included. There were 24 children and 62 adults receiving an autologous (n = 25) and allogeneic (n = 61) HSCT for malignant (n = 72) and non-malignant (n = 14) disorders. Twenty-six patients died, (10 on autologous (38%) and 16 patients (62%) on allogeneic group). The estimated overall survival (OS) at day 40 was 69%. Adults had decreased OS compared to children (66% vs 79%, p = 0.03). The severity of symptoms at the time of diagnosis, ECOG score, laboratory tests (C-reactive protein, urea values) were higher in patients who died (p < 0.05). In conclusion, HSCT recipients infected with SARS-CoV-2 have a high mortality rate mainly in adults and patients with critical initial COVID-19 presentation. These findings show the fragility of HSCT recipients with SARS-CoV-2 infection. Therefore, the importance of adherence to preventive measures is evident, in addition to prioritizing the vaccination of family members and the HSCT team.
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COVID-19 , Trasplante de Células Madre Hematopoyéticas , Adulto , Brasil/epidemiología , COVID-19/complicaciones , Niño , Humanos , SARS-CoV-2 , Tasa de SupervivenciaRESUMEN
The apple (Malus domestica Borkh) originally evolved to require temperatures below 7.2 °C for the induction of budding and flowering. In Brazil, breeders have overcome the climate barrier and developed the cultivars Anabela, Julieta, Carícia, and Eva, with low chilling requirements and good yield characteristics. These cultivars are grown in many warmer climate countries in South America, Africa, and the Middle East. The apple germplasm collection that originated these cultivars has several genotypes with pedigrees for a low chilling requirement. Knowledge of the variability and genetic relationships among these genotypes may be useful in the development of superior new cultivars. In this work, we first selected the best ISSR (inter-simple sequence repeat) primers for genetic studies in apple, and then we used the selected primers to evaluate the genetic variability of the apple germplasm collection at the Instituto Agronômico do Paraná. The evaluation of 42 ISSR primers in 10 apple genotypes allowed us to select the best nine primers based on the polymorphic information content (PIC) and resolving power (RP) indexes. The primer selection step was robust since the dendrogram obtained with the nine selected primers was the same as the one obtained using all 26 polymorphic primers. Primer selection using PIC and RP indexes allowed us to save about 60% of time and costs in the genetic variability study. The nine ISSR primers showed high levels of genetic variability in the 60 apple genotypes evaluated. The relevance of the primer selection step is discussed from the perspective of saving time and money in germplasm characterization. The high genetic variability and the genetic relationships among the genotypes are discussed from the perspective of the development of new apple cultivars, mainly aiming for a low chilling requirement that can better adapt to current climatic conditions or those that may arise with global warming.
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Prior investigations show that signaling activation through pattern recognition receptors can directly impact a number of inflammatory lung diseases. While toll-like receptor (TLR) 7 agonists have raised interest for their ability to inhibit allergen-induced pathological changes in experimental asthma conditions, the putative benefit of this treatment is limited by adverse effects. Our aim was to evaluate the therapeutic potential of two PEGylated purine-like compounds, TMX-302 and TMX-306, characterized by TLR7 partial agonistic activity; therefore, the compounds are expected to induce lower local and systemic adverse reactions. In vitro approaches and translation to murine models of obstructive and restrictive lung diseases were explored. In vitro studies with human PBMCs showed that both TMX-302 and TMX-306 marginally affects cytokine production as compared with equivalent concentrations of the TLR7 full agonist, TMX-202. The PEGylated compounds did not induce monocyte-derived DC maturation or B cell proliferation, differently from what observed after stimulation with TMX-202. Impact of PEGylated ligands on lung function and inflammatory changes was studied in animal models of acute lung injury, asthma, and silicosis following Lipopolysaccharide (LPS), allergen (ovalbumin), and silica inhalation, respectively. Subcutaneous injection of TMX-302 prevented LPS- and allergen-induced airway hyper-reactivity (AHR), leukocyte infiltration, and production of pro-inflammatory cytokines in the lung. However, intranasal instillation of TMX-302 led to neutrophil infiltration and failed to prevent allergen-induced AHR, despite inhibiting leukocyte counts in the BAL. Aerosolized TMX-306 given prophylactically, but not therapeutically, inhibited pivotal asthma features. Interventional treatment with intranasal instillation of TMX-306 significantly reduced the pulmonary fibrogranulomatous response and the number of silica particles in lung interstitial space in silicotic mice. These findings highlight the potential of TMX-306, emphasizing its value in drug development for lung diseases, and particularly silicosis.
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Aspergillosis is a mycosis that afflicts immunocompetent and immunocompromised hosts; among the former it exhibits different clinical pictures, and among the latter the infection renders an invasive form of the disease. The histologic diagnosis of invasive aspergillosis is somewhat challenging mostly because of some morphological similarities between other fungi. However, when present, the conidial heads are pathognomonic of aspergillosis. The authors present the case of a 68-year-old woman who was submitted to autologous hematopoietic stem cell transplantation in the pursuit of multiple myeloma treatment. The post-transplantation period was troublesome with the development of severe neutropenia, human respiratory syncytial virus pneumonia, and disseminated aspergillosis, which was suspected because of a positive serum galactomannan antigen determination, and resulted in a fatal outcome. The autopsy findings showed diffuse alveolar damage associated with angioinvasive pulmonary aspergillosis with numerous hyphae and conidial heads in the lung parenchyma histology. The authors call attention to the aid of autopsy in confirming the diagnosis of this deep mycosis, since only the research of the galactomannan antigen may be insufficient and uncertain due to its specificity and of the possibility of false-positive results.