Estatística geral de doação e transplantes de orgãos - Goiás - 2024 (Janeiro a julho) / General statistics on organ donation and transplants - Goiás - 2024 (January to June)

Estatística geral de doação e transplantes de orgãos - Goiás que tem como objetivos transcrever em números os resultados de todo o trabalho executado pela Gerência de Transplantes em Goiás

General statistics on organ donation and transplants - Goiás, which aims to transcribe into numbers the results of all the work carried out by the Transplant Management in Goiás

Estatística geral de doação e transplante de orgãos - Goiás - 2023 (Janeiro a dezembro) / General statistics on organ donation and transplantation - Goiás - 2023 (January to December)

Estatística geral de doação e transplantes de orgãos do Estado de Goiás que tem como objetivo transcrever em números os resultados de todo o trabalho executado pela Gerência de Transplantes em Goiás

General statistics on organ donation and transplants in the State of Goiás, which aims to transcribe into numbers the results of all the work carried out by the Transplant Management in Goiás

Estatística geral de doação e transplantes de orgãos - Goiás - 2023 (Janeiro a setembro) / General statistics on organ donation and transplants - Goiás - 2023 (January to September)

Estatística geral de doação e transplantes de orgãos - Goiás que tem como objetivo transcrever em números os resultados de todo o trabalho executado pela Gerência de Transplantes em Goiás

General statistics on organ donation and transplants - Goiás which aims to transcribe into numbers the results of all the work carried out by the Transplant Management in Goiás

Estatística geral de doação de orgãos - Goiás - 2023 (Janeiro a julho) / General organ donation statistics - Goiás - 2023 (January to July)

Estatística geral de doação de orgãos e transplantes de orgãos - Goiás tem como objetivo transcrever em números os resultados de todo o trabalho executado pela Gerência de Transplantes em Goiás

General statistics of organ donation and organ transplants - Goiás aims to transcribe in numbers the results of all the work carried out by the Transplant Management in Goiás

Operative treatments for osteochondral lesions of the talus in adults: A systematic review and meta-analysis.

PURPOSE: This systematic review aimed to identify the available evidence regarding the comparative effectiveness and safety of various operative treatments in adult patients with osteochondral lesions of the talus (OLT). MATERIALS AND METHODS: The PubMed, Embase, ISI Web of Knowledge, and the Cochrane Controlled Trial Register of Controlled Trials were searched from their inception date to September 2019. Two reviewers selected the randomized controlled trials (RCTs) and non-RCTs assessing the comparative effectiveness and safety of various operative treatments for OLT. The meta-analysis was performed using Revman 5.3. RESULTS: Eight studies (1 RCT and 7 non-RCTs) with 375 patients were included in this review. The difference in the American Orthopaedic Foot and Ankle Society (AOFAS) score between the cartilage repair and replacement was not significant. The cartilage regeneration with or without cartilage repair had significant superiority in improving the AOFAS score compared with the cartilage repair. The difference in the magnetic resonance observation of cartilage repair tissue score between the cartilage repair and replacement and between cartilage repair and cartilage repair plus regeneration was significant. CONCLUSIONS: Cartilage regeneration and cartilage repair plus regeneration had significant superiority in improving the ankle function and radiological evaluation of OLT, although the trials included did not have high-level evidence. Moreover, which treatment between the 2 was safer could not be addressed in this review as most of the trials did not report the safety outcome. Further studies are needed to define the best surgical option for treating OLT.

Changes in Hematopoietic Cell Transplantation Practices in Response to COVID-19: A Survey from the Worldwide Network for Blood & Marrow Transplantation.

SARS-CoV-2 has spread rapidly worldwide, but the full impact of the COVID-19 pandemic on the field of hematopoietic cell transplantation (HCT) remains unknown. To understand this better, an 18-item online survey was disseminated by the Worldwide Network for Blood & Marrow Transplantation with questions exploring SARS-CoV-2 testing algorithms, mobilization, and cryopreservation strategies and COVID-19 infections in allogeneic related and autologous hematopoietic progenitor cell (HPC) donors. The aim of this survey was to assess the impact of the outbreak on policies relating to HPC mobilization, collection, and processing with respect to changes in daily routine. A total of 91 individual responses from distinct centers in 6 continents were available for analysis. In these centers, the majority (72%) of allogeneic related and autologous donors are routinely tested for SARS-CoV-2 before HPC collection, and 80% of centers implement cryopreservation of allogeneic HPC grafts before commencing conditioning regimens in patients. Five related and 14 autologous donors who tested positive for COVID-19 did not experience any unexpected adverse events or reactions during growth factor administration (eg, hyperinflammatory syndrome). These data are limited by the small number of survey respondents but nonetheless suggest that centers are following the recommendations of appropriate scientific organizations and provide some preliminary data to suggest areas of further study.

Protective effect of bone marrow mesenchymal stem cell-derived exosomes against the reproductive toxicity of cyclophosphamide is associated with the p38MAPK/ERK and AKT signaling pathways.

Spermatogenic dysfunction caused by cyclophosphamide (CP) chemotherapy has seriously influenced the life quality of patients. Unfortunately, treatments for CP-induced testicular spermatogenic dysfunction are limited, and the molecular mechanisms are not fully understood. For the first time, here, we explored the effects of bone marrow mesenchymal stem cell-derived exosomes (BMSC-exos) on CP-induced testicular spermatogenic dysfunction in vitro and in vivo. BMSC-exos could be taken up by spermatogonia (GC1-spg cells). CP-injured GC1-spg cells and BMSC-exos were cocultured at various doses, and then, cell proliferation was measured using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. In addition, photophosphorylation of extracellular-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), and protein kinase B (AKT) proteins was evaluated by western blotting as well as apoptosis in GC1-spg cells measured using flow cytometry. Treatment with BMSC-exos enhanced cell proliferation and reduced apoptosis of CP-injured GCI-spg cells. Phosphorylated levels of ERK, AKT, and p38MAPK proteins were reduced in CP-injured spermatogonia when co-treated with BMSC-exos, indicating that BMSC-exos acted against the reproductive toxicity of CP via the p38MAPK/ERK and AKT signaling pathways. In experiments in vivo, CP-treated rats received BMSC-exos by injection into the tail vein, and testis morphology was compared between treated and control groups. Histology showed that transfusion of BMSC-exos inhibited the pathological changes in CP-injured testes. Thus, BMSC-exos could counteract the reproductive toxicity of CP via the p38MAPK/ERK and AKT signaling pathways. The findings provide a potential treatment for CP-induced male spermatogenic dysfunction using BMSC-exos.

Haplo-identical or mismatched unrelated donor hematopoietic cell transplantation for Fanconi anemia: Results from the Severe Aplastic Anemia Working Party of the EBMT.

Allogeneic hematopoietic cell transplantation (HCT) is the only curative option for bone marrow failure or hematopoietic malignant diseases for Fanconi anemia (FA) patients. Although results have improved over the last decades, reaching more than 90% survival when a human leukocyte antigen (HLA)-identical donor is available, alternative HCT donors are still less reported. We compared HCT outcomes using HLA-mismatched unrelated donors (MMUD; n = 123) or haplo-identical donors (HDs), either using only in vivo T cell depletion (n = 33) or T cells depleted in vivo with some type of graft manipulation ex vivo (n = 59) performed for FA between 2000 and 2018. Overall survival (OS) by 24 months was 62% (53-71%) for MMUD, versus 80% (66-95%) for HDs with only in vivo T cell depletion and 60% (47-73%) for HDs with in vivo and ex vivo T cell depletion (p = .22). Event-free survival (EFS) was better for HD-transplanted FA patients with only in vivo T cell depletion 86% (73-99%) than for those transplanted from a MMUD 58% (48-68%) or those with graft manipulation 56% (42-69%) (p = .046). Grade II-IV acute graft-versus-host disease (GVHD) was 41% (MMUD) versus 40% (HDs with no graft manipulation) versus 17% (HDs with T cell depleted graft), (p = .005). No differences were found for the other transplant related outcomes. These data suggest that HDs might be considered as an alternative option for FA patients with better EFS using unmanipulated grafts.

Predictive factors for the development of anemia after hematopoietic stem cell donation.

BACKGROUND: Although Hematopoietic Stem Cells (HSC) donation through bone marrow (BM) and peripheral blood (PB) are usually safe procedures, adverse events are expected. One of the most common events especially among BM donors (BMD) is the development of anemia. To protect the BMD and preserve the hemoglobin levels, many centers collect autologous pre-procedure blood, but the actual benefits of this procedure is controversial. METHODS AND MATERIALS: This study analyzed retrospectively data to observe what factors may influence the occurrence of post-donation anemia and also evaluate the relevance of autologous red blood cell pre procedure donation (PAD). RESULTS: The development of immediately post donation anemia (IP) was higher in BMD than in PB donors (64.2% BMD and 10.7% PBD, P < .001) and also in late post donation (LP) (28.4% BMD and 3.6% PBD, P = .007). The study demonstrated an association between PAD and anemia in IP (72.7% with anemia and 27.3% without anemia, P = .006) and an association between the volume of red blood cells in the donated hematopoietic product and the development of anemia in LP (356.3 mL and 297.8 mL, P = .037). CONCLUSION: In conclusion, collection of HSC through BM is a risk factor for anemia and PAD is a risk factor for IP anemia.

Inmunodeficiencia Combinada Severa, reporte de pacientes chilenos diagnosticados durante el período 1999-2020 / Severe combined immunodeficiency, report of Chilean patients diagnosed during the 1999-2020 period

INTRODUCCIÓN: La inmunodeficiencia combinada severa (IDCS) corresponde a una de las formas más graves de inmunodeficiencia primaria, existiendo escasos datos nacionales sobre ésta. OBJETIVO: describir la epidemiología, complicaciones, pronóstico y uso de la vacuna BCG en pacientes chilenos con IDCS. PACIENTES Y MÉTODO: Estudio retrospectivo de pacientes diagnosticados con IDCS entre los años 1999 y 2020 por médicos inmunólogos a lo largo de Chile. El diagnóstico de IDCS se realizó conforme a los criterios propuestos por Shearer: linfocitos T (CD3+) < 300 células/μL y prolife ración 10% del límite de normalidad en respuesta a fitohemaglutinina o presencia de linfocitos T de origen materno. Se obtuvieron de la ficha clínica los datos correspondientes a: sexo, edad al diagnóstico, consanguinidad, región de origen, subpoblaciones linfocitarias, diagnóstico genético, complicaciones infecciosas y no infecciosas, vacunación BCG y sus complicaciones, edad de deriva ción al centro de TPH y causa de mortalidad no relacionada al TPH. RESULTADOS: se diagnosticaron 25 casos de IDCS en 22 familias entre los años 1999-2020. 78% varones, la edad media a la primera manifestación fue 2.3 meses (0-7), mientras que la edad media al diagnóstico fue de 3.4 meses (0 7). Un 16% de los casos tenía un antecedente familiar de IDCS. Un 40% de los casos fueron diag nosticados en la Región Metropolitana. El inmunofenotipo más frecuente fue T-B-NK+ (48%). Se realizaron estudios genéticos en 69,5% de los casos, siendo los defectos genéticos en RAG2 (39%) la causa más frecuente. Un 88% de los casos recibió la vacuna Bacillus Calmette-Guerin (BCG) previo al diagnóstico, incluidos 2 pacientes con historia familiar positiva, 36% de los vacunados experimentó complicaciones de la BCG. La edad media a la derivación a trasplante fue de 7,4 meses (5-16). De los 25 pacientes, 11 fallecieron previo a la derivación a un centro de trasplante. CONCLUSIÓN: En Chile existe un retraso clínicamente significativo entre las primeras manifestaciones y el diagnóstico de IDCS, así como un importante retraso en la derivación a centros de trasplante. La mayoría de los pacientes con IDCS reciben la vacuna BCG, pese a tener antecedentes familiares, y experimentan frecuentemente complicaciones de la vacuna.

INTRODUCTION: Severe combined immunodeficiency (SCID) is the most severe form of primary immunodeficiency. To date, there is little local information about this disease. OBJECTIVE: To describe the epidemiology, complications, prognosis, and use of the BCG vaccine in Chilean patients with SCID. PATIENTS AND METHOD: Retrospective review of the clinical records of patients diagnosed with SCID by clinical immunologists between 1999 and 2020 throughout Chile. SCID was diagnosed according to the cri teria proposed by Shearer: T lymphocytes (CD3+) < 300 cells/μL and proliferation 10% of the limit of normality in response to phytohemagglutinin or presence of T lymphocytes of maternal origin. Data collected from the clinical records were: sex, age at diagnosis, consanguinity, region of origin, lymphocyte subpopulations, genetic diagnosis, infectious and non-infectious complications, BCG vaccination and its complications, age at referral to the bone marrow transplant (BMT) center, and cause of non-BMT-related mortality. RESULTS: Between 1999 and 2020, 25 patients were diagnosed with SCID. 78% of them were male, mean age at first manifestation of the disease was 2.3 months (0-7), while the mean age at diagnosis was 3.4 months (0-7). 16% of patients had a family history of SCID. 40% of cases were diagnosed within the Metropolitan Region. The most frequent immuno- phenotype was T-B-NK+ SCID (48%). Genetic studies were done in 69.5% of cases, mutations in the RAG2 gene were the most common etiology of SCID (39%). 88% of SCID patients received the Bacillus Calmette-Guerin (BCG) vaccine before diagnosis, including 2 cases with a known family history of SCID. 36% of those who received the vaccine had BCG-related complications. The mean age at referral to a bone marrow transplant center was 7.4 months (5-16). 11/25 patients died before being transferred to a transplant center. DISCUSSION: There is a clinically significant delay between the first manifestations and the diagnosis of SCID in Chilean patients, as well as an important time gap between the diagnosis of SCID and referral to a center for BMT. Most SCID cases in Chile receive the BCG vaccine, despite a known family history of the disease, and frequently develop vaccine-related complications.

Anemia aplásica en población pediátrica de Costa Rica: experiencia de 10 años / Aplastic anemia in Costa Rican pediatric population: a 10 year experience

Resumen Objetivo: La anemia aplásica es una enfermedad rara, potencialmente mortal sin diagnóstico y tratamiento temprano. El objetivo del estudio fue describir la epidemiología de la anemia aplásica en la población de 0 a 13 años a nivel nacional, atendida en el Hospital Nacional de Niños "Dr. Carlos Sáenz Herrera", de la Caja Costarricense de Seguro Social, único centro del país disponible para la atención en hematología pediátrica. Métodos: Se realizó un estudio observacional retrospectivo de los pacientes atendidos en el Servicio de Hematología Pediátrica, con diagnóstico de anemia aplásica adquirida y las diversas formas de aplasias congénitas, en el periodo de enero 2006 a junio de 2016. Se registró el tipo de tratamiento recibido, su respuesta y la mortalidad asociada con la enfermedad, así como algunos datos epidemiológicos. Resultados: Se analizó un total de 27 casos, 23 con anemia aplásica adquirida y 4 con diversos tipos de anemias congénitas. La edad media al momento del diagnóstico fue de 81,7 meses, con una relación hombre: mujer de 1.1:1. De los 23 pacientes con anemia aplásica adquirida, 10 recibieron tratamiento con globulina antitimocito y presentaron respuesta a la globulina equina 2/5 pacientes como primera línea de tratamiento y 1 como segunda línea; con la globulina de conejo se obtuvo respuesta en 1/5 pacientes como primera línea y en 2 como segunda línea. Tres pacientes recibieron tratamiento con trasplante de médula ósea y presentaron una respuesta completa, sin evidenciar datos de enfermedad de injerto versus huésped u otras complicaciones al finalizar el estudio. No se logró demostrar diferencia significativa respecto al sexo, edad de diagnóstico, valores del hemograma, frecuencia de requerimiento de plaquetas o glóbulos rojos, grado de severidad ni mortalidad. Conclusión: Se confirmó la baja prevalencia de la anemia aplásica; la muestra obtenida durante el periodo analizado es pequeña y limita la observación de características relevantes ante referentes internacionales.

Abstract Objective: Aplastic anemia is a rare and life-threatening disease without diagnosis and early treatment. The objective of this study was to describe the epidemiological characters of patients with aplastic anemia and 0-13 years old in Costa Rica, to treat in the Hospital Nacional de Niños Dr.Carlos Sáenz Herrera, CajaCostarricense de Seguro Social; only there offers Pediatric Hematology service. Methods: We performed an observational retrospective study, there including the patients diagnosed with both acquired aplastic anemia and inherited bone marrow failure syndromes from January 2006 to June 2016, regardless of sex or ethnicity. We evaluated the treatment received, the response to each treatment, and mortality associated with the disease. Results: An overall of 27 patients were included, 23 diagnosed with acquired aplastic anemia and, 4 with bone marrow failure syndrome. The mean age of diagnosis was 81.7 months, with a male to female ratio of 1.1:1. Of the 23 patients diagnosed with acquired aplastic anemia, 10 received immunosuppressive therapy with antithymocite globulin, with a response to horse globulin as a first line treatment in 2/5 patients, and 1 as a second line treatment. Patients with rabbit globulin showed to response in 1/5 cases when used as a first line treatment, and a response as a second line treatment after a no response treatment with horse globulin in 2/3 patients. Three patients treated with a matched related donor bone marrow transplant and showed complete response, without complications including graft versus host disease by the end of the study period. There was no statistical difference regarding sex, age of diagnosis, blood cell counts, frequency of blood product transfusions, degree of severity associated or, mortality. Conclusions: Our results confirm the low incidence of aplastic anemia, it's a little study population and has limited results of relevant characteristics and can´t compare with international studies.

Total Body Irradiation and Risk of Breast Cancer After Blood or Marrow Transplantation: A Blood or Marrow Transplantation Survivor Study Report.

PURPOSE: To examine the association between total body irradiation (TBI) and subsequent breast cancer in women treated with blood or marrow transplantation (BMT) for hematologic malignancies. PATIENTS AND METHODS: Participants were drawn from the BMT Survivor Study (BMTSS), a retrospective cohort study that included patients who underwent transplantation between 1974 and 2014 and survived for ≥ 2 years after BMT. Patients with pre-BMT chest radiation or a history of breast cancer were excluded. Participants completed the BMTSS survey, which included details regarding breast cancer diagnosis. Subsequent breast cancer was confirmed by pathology report review or physician notes. Cox proportional hazards models assessed the association between TBI and subsequent breast cancer. Standardized incidence ratios were calculated to determine the excess risk of subsequent breast cancer compared with that in the general population. RESULTS: A total of 1,464 female BMT survivors (allogeneic: n = 788; autologous: n = 676) participated, with a median follow-up of 9.3 years from BMT. TBI was used in 660 patients (46%). Thirty-seven women developed subsequent breast cancer (allogeneic: n = 19; autologous: n = 18). Multivariable analysis revealed that exposure to TBI was associated with an increased risk of subsequent breast cancer among allogeneic BMT survivors (hazard ratio [HR], 3.7 [95% CI, 1.2 to 11.8]; P = .03) and autologous BMT survivors (HR, 2.6 [95% CI, 1.0 to 6.8]; P = .048). Pre-BMT exposure to alkylating agents was associated with an increased risk of subsequent breast cancer among autologous BMT survivors (HR, 3.3 [95% CI, 1.0 to 9.0]; P = .05). Compared with that in the general population, exposure to TBI at age < 30 years was associated with a 4.4-fold higher risk of subsequent breast cancer in allogeneic BMT survivors and a 4.6-fold higher risk in autologous BMT survivors. CONCLUSION: The association between TBI and subsequent breast cancer, especially among those exposed at a young age, as well as pre-BMT exposure to alkylating agents, should inform breast cancer screening for early detection.

How the COVID-19 pandemic changed cellular therapy at Columbia University Irving Medical Center/NewYork-Presbyterian Hospital.

New York is at the epicenter of the coronavirus disease 2019 (COVID-19) pandemic caused by the SARS-CoV-2 virus. Columbia University Irving Medical Center/NewYork-Presbyterian Hospital (CUIMC/NYPH) had to make changes to its cellular therapy operations to ensure patient, donor, and staff safety and well-being. In this article, we discuss the process changes we instituted for cellular therapy clinical care, collection, processing, and cryopreservation to cope with the rapidly evolving pandemic.

Hematopoietic cell infusion-related adverse events in pediatric/small recipients in a prospective/multicenter study.

BACKGROUND: Hematopoietic cell infusion-related adverse events (HCI-AEs) in hematopoietic stem cell transplantations (HSCTs) have been largely attributed to toxicity of dimethyl sulfoxide (DMSO) for cryopreservation, but HSC products also contain various cells and plasma components. Our recent prospective study of 1125 HSCT recipients revealed the highest overall HCI-AE rate in bone marrow transplantation (BMT) using fresh/noncryopreserved products, although products of peripheral blood stem cell transplantation and cord blood transplantation (CBT) are generally cryopreserved with DMSO containing smaller plasma volumes. We aimed to clarify if product volume and component effects are more substantial in small recipients including children. STUDY DESIGN AND METHODS: We performed subgroup analysis on 219 recipients of 45 kg or less body weight (whole small recipients), including 90 children (pediatric recipients), from the original cohort (general recipients). RESULTS: Whereas overall HCI-AE rates did not differ among hematopoietic stem cell sources in the general recipients, bradycardia most often occurred after CBT in whole small recipients. Conversely, whole small and general recipients shared the same trend of having the highest rate of hypertension in BMT. The overall HCI-AE rate was higher in allogeneic HSCT compared with autologous HSCT. Notably, pediatric recipients showed a 10-fold higher incidence of nausea and vomiting in allogeneic HSCT compared with autologous HSCT, suggesting a possible role of allogeneic antigens. Multivariate analysis identified a relatively large infusion volume per body weight as a significant factor correlating with HCI-AE in whole small recipients. CONCLUSIONS: We should be aware of product volume and specific HCI-AEs such as nausea and vomiting in small patients including children.

Patients' quality of life: Validation of the functional assessment of cancer therapy-bone marrow transplant (FACT-BMT) instrument for the Mexican population.

OBJECTIVE: The functional assessment of cancer therapy-bone marrow transplant (FACT-BMT) is a widely used instrument to assess quality of life (QOL) in hematopoietic stem cell transplant (HSCT) patients, but there is little evidence of its validity in Latin American populations. This study evaluated the psychometric properties of the Spanish language version of the FACT-BMT in Mexican patients. METHOD: First, the original version was piloted with 15 HSCT patients to obtain an adequate cultural version, resulting in the adaptation of one item. After that, the new version was completed by 139 HSCT patients. RESULTS: The results showed a FACT factor structure that explains 70.84% of the total variance, a factor structure similar to the original FACT structure, and with a high internal consistency (Cronbach's alpha = 0.867). For the BMT subscale, the best factor structure included 17 items which explain 61.65% of the total variance with an adequate internal consistency (Cronbach's alpha = 0.696). SIGNIFICANCE OF THE RESULTS: The FACT-BMT was found to be a valid and reliable instrument to evaluate QOL in Mexican patients. Our results constitute new FACT-BMT empirical evidence that supports its clinical and research uses.

Ultrasound is superior to palpation for thyroid cancer detection in high-risk childhood cancer and BMT survivors.

PURPOSE: Thyroid cancer is a common subsequent malignant neoplasm in childhood cancer survivors (CCS). Patients who received radiotherapy (RT) to the head, neck, upper thorax, or total body irradiation (TBI) are considered to be at risk for subsequent thyroid cancer. Current Children's Oncology Group screening guidelines recommend annual neck palpation. Our objective was to determine if ultrasound (US) is more sensitive and specific than palpation to detect thyroid cancer in high-risk CCS and bone marrow transplant (BMT) survivors. METHODS: Electronic medical records of patients followed in a longitudinal survivorship clinic from January 1, 2010 to December 31, 2017 were reviewed. Inclusion criteria included history of RT to the head, neck, upper thorax, or TBI for primary therapy or preparation for BMT prior to the age of 20 years. RESULTS: Two hundred and twenty-five patients had documented palpation and 144 (64%) also had US evaluation. Mean radiation dose was 28.6 Gy. Sixteen of 225 patients (7.1%) developed a subsequent thyroid cancer at a mean of 9.7 years from the completion of RT. Sensitivity of US was 100% compared with 12.5% for palpation. US demonstrated higher accuracy, with a receiver operating characteristic (ROC) area under the curve (AUC) of 0.87 versus 0.56 for palpation (P < 0.0001). CONCLUSION: Routine screening with US was more sensitive than palpation for detection of subsequent thyroid cancer after high-risk RT in CCS and BMT survivors. Screening US may lead to earlier detection of thyroid cancer in this population. Earlier diagnosis has the potential to decrease operative complexity, and earlier definitive therapy reduces the likelihood of metastatic disease.

Clinical and Genetic Risk Prediction of Cognitive Impairment After Blood or Marrow Transplantation for Hematologic Malignancy.

PURPOSE: Using a candidate gene approach, we tested the hypothesis that individual single nucleotide polymorphisms (SNPs) and gene-level variants are associated with cognitive impairment in patients with hematologic malignancies treated with blood or marrow transplantation (BMT) and that inclusion of these SNPs improves risk prediction beyond that offered by clinical and demographic characteristics. PATIENTS AND METHODS: In the discovery cohort, BMT recipients underwent a standardized battery of neuropsychological tests pre-BMT and at 6 months, 1 year, 2 years, and 3 years post-BMT. Associations between 68 candidate genes and cognitive impairment were assessed using generalized estimating equation models. Elastic-Net regression was used to build Base (sociodemographic), Clinical, and Combined (Base plus Clinical plus genetic) risk prediction models of post-BMT impairment. An independent nonoverlapping cohort from the BMT Survivor Study with self-report of learning/memory problems (as identified by their health care provider) was used for model replication. RESULTS: The discovery cohort included 277 participants (58.5% males; 68.6% non-Hispanic whites; and 46.6% allogeneic BMT recipients). Adjusting for BMT type, age at BMT, sex, race/ethnicity, and cognitive reserve, SNPs in the blood-brain barrier, telomere homeostasis, and DNA repair genes were significantly associated with cognitive impairment. Compared with the Clinical Model, the Combined Model had higher predictive power in both the discovery cohort (mean area under the receiver operating characteristic curve [AUC], 0.89; 95% CI, 0.85 to 0.93 v 0.77; 95% CI, 0.71 to 0.83; P = 1.24 × 10-9) and the replication cohort (AUC, 0.71; 95% CI, 0.66 to 0.76 v 0.63; 95% CI, 0.57 to 0.68; P = .004). CONCLUSION: Inclusion of candidate genetic variants enhanced the prediction of risk of post-BMT cognitive impairment beyond that offered by demographic/clinical characteristics and represents a step toward a personalized approach to managing patients at high risk for cognitive impairment after BMT.

[Severe combined immunodeficiency, report of chilean patients diagnosed during the 1999-2020 period]. / Inmunodeficiencia Combinada Severa, reporte de pacientes chilenos diagnosticados durante el período 1999-2020.

INTRODUCTION: Severe combined immunodeficiency (SCID) is the most severe form of primary immunodeficiency. To date, there is little local information about this disease. OBJECTIVE: To describe the epidemiology, complications, prognosis, and use of the BCG vaccine in Chilean patients with SCID. PATIENTS AND METHOD: Retrospective review of the clinical records of patients diagnosed with SCID by clinical immunologists between 1999 and 2020 throughout Chile. SCID was diagnosed according to the cri teria proposed by Shearer: T lymphocytes (CD3+) < 300 cells/µL and proliferation 10% of the limit of normality in response to phytohemagglutinin or presence of T lymphocytes of maternal origin. Data collected from the clinical records were: sex, age at diagnosis, consanguinity, region of origin, lymphocyte subpopulations, genetic diagnosis, infectious and non-infectious complications, BCG vaccination and its complications, age at referral to the bone marrow transplant (BMT) center, and cause of non-BMT-related mortality. RESULTS: Between 1999 and 2020, 25 patients were diagnosed with SCID. 78% of them were male, mean age at first manifestation of the disease was 2.3 months (0-7), while the mean age at diagnosis was 3.4 months (0-7). 16% of patients had a family history of SCID. 40% of cases were diagnosed within the Metropolitan Region. The most frequent immuno- phenotype was T-B-NK+ SCID (48%). Genetic studies were done in 69.5% of cases, mutations in the RAG2 gene were the most common etiology of SCID (39%). 88% of SCID patients received the Bacillus Calmette-Guerin (BCG) vaccine before diagnosis, including 2 cases with a known family history of SCID. 36% of those who received the vaccine had BCG-related complications. The mean age at referral to a bone marrow transplant center was 7.4 months (5-16). 11/25 patients died before being transferred to a transplant center. DISCUSSION: There is a clinically significant delay between the first manifestations and the diagnosis of SCID in Chilean patients, as well as an important time gap between the diagnosis of SCID and referral to a center for BMT. Most SCID cases in Chile receive the BCG vaccine, despite a known family history of the disease, and frequently develop vaccine-related complications.

[A monocentric study on the management of patients with myelodysplastic syndromes in Morocco]. / Prise en charge des syndromes myélodysplasiques au Maroc à propos d´une étude mono-centrique.

We conducted a retrospective descriptive analytical study in the Department of Clinical Haematology at the Mohammed V Military Training Hospital in Rabat over a period of 10 years. This study included 76 patients diagnosed with myelodysplastic syndrome (MDS) between 2008 and 2018. The average number of cases per year was 7.6. Out of 76 patients, 57% were men and 43% were women. The average age of our study population was 65.75 ± 12.55. The average age was 66.88 ± 13.10. No cases of profession exposed to disease was reported. Ninety-seven point three percent of patients had primary myelodysplastic syndrome and only 2 or 2.7% had myelodysplastic syndrome secondary to chemotherapy. The average time between the first visit and the diagnosis of myelodysplastic syndrome was, on average, 33.6 days ± 51, with a median of 19 days. The IPSS prognostic score was: low risk in 37.4% of cases, intermediate risk 1 in 46.6% of cases, intermediate risk in 12% of cases and high risk in 4% of cases. Thus, 84% of patients had low-risk MDS and 16% had high-risk MDS. Regular monitoring of patients showed many complications such as bleeding in 13% of patients, infections in 8% of cases, secondary hemochromatosis as a result of iterative transfusions in 6.6% of patients and transformation to acute myeloid leukemia in 2.7% of patients. In our study, abstention was the therapeutic choice in 42.1% of patients, transfusion was recommended in 35.5% of patients: red cells in 70% of cases, platelet concentrates in 40% of cases, iron chelators in 25% of transfused patients and EPO in 27% of patients. azacitidine was prescribed in 18% of patients, 50% had low-risk MDS and 50% had high-risk MDS. Bone marrow transplant was the only curative treatment for MDS. It was performed in a single patient with high risk MDS.