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1.
Pediatr Blood Cancer ; 70(3): e30193, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36583456

RESUMO

Vulnerable patient populations have seen decreased rates of vaccination against SARS-CoV2-19 (COVID-19) due to hesitancies and distrust, magnified by a paucity of data for certain populations. The rate of COVID-19 vaccination in children with sickle cell disease (SCD) remains low despite the risk for severe complications, resulting in continued infections and hospitalizations from COVID-19. We sought to describe vaccine reactions, including vaso-occlusive crises, emergency department visits, and hospitalizations, in children with SCD. Our findings will start to provide the necessary vaccine side effect data to inform patients, caregivers, and clinicians considering the COVID-19 primary vaccination series.


Assuntos
Anemia Falciforme , Vacinas contra COVID-19 , COVID-19 , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Criança , Humanos , Anemia Falciforme/terapia , Anemia Falciforme/tratamento farmacológico , COVID-19/epidemiologia , COVID-19/prevenção & controle , COVID-19/complicações , Vacinas contra COVID-19/efeitos adversos , RNA Viral/uso terapêutico , SARS-CoV-2
2.
Pediatr Blood Cancer ; 70(1): e29961, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36094289

RESUMO

Sickle cell disease (SCD) requires coordinated, specialized medical care for optimal outcomes. There are no United States (US) guidelines that define a pediatric comprehensive SCD program. We report a modified Delphi consensus-seeking process to determine essential, optimal, and suggested elements of a comprehensive pediatric SCD center. Nineteen pediatric SCD specialists participated from the US. Consensus was predefined as 2/3 agreement on each element's categorization. Twenty-six elements were considered essential (required for guideline-based SCD care), 10 were optimal (recommended but not required), and five were suggested. This work lays the foundation for a formal recognition process of pediatric comprehensive SCD centers.


Assuntos
Anemia Falciforme , Criança , Humanos , Consenso , Anemia Falciforme/terapia
4.
Pediatr Blood Cancer ; 70(1): e30046, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36322607

RESUMO

INTRODUCTION: There is limited understanding of pain, patient-reported outcomes (PROs) of health-related quality of life (HRQoL), psychological factors, and experimental pain sensitivity before and following hematopoietic cell transplant (HCT) in children with sickle cell disease (SCD). METHODS: Individuals aged 8 years and older, English speaking, and scheduled for a HCT were invited to participate in an observational study where they completed assessments of pain, PROs, psychological factors, and qualitative interviews before and around 3 months, 6 months, 1 year, and 2 years post-HCT. An optional substudy of experimental pain sensitivity before and around 6 month, 1 year, and 2 years post-HCT was also offered. RESULTS: Data from eight participants (median age 13.5 years, 25% female) with sickle cell anemia (SCA) or similarly severe genotype, and successful donor-derived erythropoiesis post-HCT are reported. We found that collection of pain, PROs, psychological factors, and qualitative data were feasible in the context of HCT. We found moderate to large differences in pain and some PROs between baseline to 1 year and baseline to 2 year post-HCT based on effect sizes, but only some differences were statistically significant. We found moderate to large differences in pressure pain threshold and moderate differences in cold pain threshold between baseline to 1 year and baseline to 2 year post-HCT based on effect sizes, but these differences were not statistically significant. Qualitative data indicated an improvement in pain and HRQoL post-HCT. CONCLUSION: This study provides a framework for the conduct of multimodal pain assessments before and after HCT, which is feasible but faced with unique barriers.


Assuntos
Anemia Falciforme , Transplante de Células-Tronco Hematopoéticas , Criança , Feminino , Humanos , Adolescente , Masculino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Qualidade de Vida , Condicionamento Pré-Transplante , Anemia Falciforme/terapia , Dor
5.
Pediatr Blood Cancer ; 70(3): e30125, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36518026

RESUMO

INTRODUCTION: Patients with sickle cell disease (SCD) need frequent health maintenance visits and may face barriers accessing care. Telemedicine, during COVID pandemic, has provided a unique model of care to improve access; however, potential barriers and satisfaction with its use in SCD have not been fully evaluated. OBJECTIVE: To determine caregiver, patient, and healthcare provider (HCP) perspectives and satisfaction with telemedicine in healthcare delivery. METHODS: We surveyed patients with SCD, caregivers, and HCP, who participated in at least one telemedicine visit from March 2020 to June 2021, using the Telemedicine Usability Questionnaire (TUQ). We also accessed and compared the Press Ganey surveys completed by families who completed a telemedicine or in-person visit. Data were summarized using descriptive statistics. The internal reliability of TUQ was assessed using Cronbach's coefficient alpha. Press Ganey data comparing satisfaction with telemedicine versus in-person visits were analyzed by Mann-Whiney U test. RESULTS: Fifty-two patients/caregivers and 10 HCP completed the survey. Patients/caregivers rated satisfaction "excellent" in the five areas (Usefulness, Ease of use, Effectiveness, Reliability and Satisfaction). HCP rated Usefulness, Ease of use, Effectiveness, Satisfaction as "good," and Reliability as "excellent." Press Ganey scores for satisfaction with care for telemedicine and in-person visits were not statistically different (p > .05). DISCUSSION: We found high satisfaction for caregivers and patients as well as HCP in the delivery of clinical services via telemedicine for SCD. We suggest that telemedicine is a viable option for this population and may help overcome the barriers SCD families often face accessing care.


Assuntos
Anemia Falciforme , COVID-19 , Telemedicina , Humanos , COVID-19/epidemiologia , Reprodutibilidade dos Testes , Satisfação do Paciente , Anemia Falciforme/terapia , Pais
6.
Curr Opin Hematol ; 30(1): 22-27, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36539362

RESUMO

As cellular therapies gradually become the mainstay of treatment for several nonmalignant diseases, there appears to be varied accessibility to these therapies globally. Despite considerable burden of nonmalignant conditions, such as sickle cell disease, thalassemia, and aplastic anemia in populations of low-middle-income countries, the utilization of cellular therapies remain sparse because of lack of resources. Globally, the frequency of hematopoietic stem cell transplant (HSCT) has increased disproportionately in countries with higher gross national income (GNI) per capita, governmental healthcare expenditures, and a high human development index. This leads to a large subset of international patients seeking care in the United States. This review summarizes the unique set of challenges that often arise when offering sophisticated therapies such as HSCT to international patients constituting of cross-cultural, logistical, financial, and medical challenges and the opportunities that are available to bridge the gap.


Assuntos
Anemia Aplástica , Anemia Falciforme , Transplante de Células-Tronco Hematopoéticas , Humanos , Renda , Gastos em Saúde , Anemia Falciforme/terapia
7.
Pediatr Blood Cancer ; 70(2): e30089, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36495544

RESUMO

Social determinants of health (SDoH) may impact outcomes in sickle cell disease (SCD). We conducted a comprehensive literature review of five electronic databases to elucidate the relationship between SDoH and SCD, and identify gaps in the literature. Our search yielded 59 articles, which we organized into five SDoH areas: Neighborhood and Built Environment, Health and Healthcare, Social and Community Context, Education, and Economic Stability. We found that social determinants, such as access to healthcare, were inconsistently evaluated. Improved recognition and understanding of SDoH should enhance the development of programs that directly address its detrimental effects on patients with SCD.


Assuntos
Anemia Falciforme , Determinantes Sociais da Saúde , Humanos , Escolaridade , Características de Residência , Anemia Falciforme/epidemiologia , Anemia Falciforme/terapia
8.
Pediatr Blood Cancer ; 70(3): e30178, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36583467

RESUMO

This review aimed to identify and describe individual-level behavioral interventions for children 0-18 years of age with sickle cell disease (SCD). PRISMA guidelines were followed at each stage of this review. Twenty-seven studies were included, representing six intervention types: disease knowledge (n = 7), self-management (n = 7), pain management (n = 4), school functioning (n = 4), cognitive health (n = 4), and mental health (n = 2). Most interventions targeted older children (5+ years), while only two examined interventions for children 0-3 years. This review suggests that offering education about disease knowledge, self-management, and pain management interventions can be beneficial for this population. Future research is needed to understand interventions to support young children and the impact of SCD on development.


Assuntos
Anemia Falciforme , Autogestão , Criança , Humanos , Adolescente , Pré-Escolar , Anemia Falciforme/terapia , Terapia Comportamental , Manejo da Dor , Instituições Acadêmicas
9.
Hematology Am Soc Hematol Educ Program ; 2022(1): 450-458, 2022 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-36485155

RESUMO

Ischemic priapism is a common but underrecognized morbidity affecting about 33% of adult men with sickle cell disease (SCD). The onset of priapism occurs in the prepubertal period and tends to be recurrent with increasing age. Significantly, priapism is associated with an unrecognized high burden of mental duress and sexual dysfunctions. The diagnosis of priapism is clinical. Many episodes of priapism will resolve spontaneously, but when an episode lasts longer than 4 hours, the episode is considered a urologic emergency requiring quick intervention with either corporal aspiration or shunt surgery. Only 3 randomized clinical trials (stilbesterol, ephedrine or etilefrine, and sildenafil) have been conducted for secondary priapism prevention in SCD. All 3 trials were limited with small sample sizes, selection biases, and inconclusive results after completion. The current molecular understanding of the pathobiology of priapism suggests a relative nitric oxide (NO) deficiency secondary to chronic hemolysis in SCD and associated phosphodiesterase type 5 dysregulation. We posit an increase in NO levels will restore the normal homeostatic relationship between voluntary erection and detumescence. Currently, 2 randomized phase 2 trials (1 double-blind, placebo-controlled trial and 1 open-label, single-arm intervention) are being conducted for secondary priapism prevention in men at high risk for recurrent priapism (NCT03938454 and NCT05142254). We review the epidemiology and pathobiology of priapism, along with mechanistic therapeutic approaches for secondary prevention of priapism in SCD.


Assuntos
Anemia Falciforme , Etilefrina , Priapismo , Adulto , Masculino , Humanos , Priapismo/epidemiologia , Priapismo/etiologia , Priapismo/terapia , Anemia Falciforme/complicações , Anemia Falciforme/epidemiologia , Anemia Falciforme/terapia , Citrato de Sildenafila/uso terapêutico , Etilefrina/uso terapêutico , Hemólise , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
Hematology Am Soc Hematol Educ Program ; 2022(1): 459-466, 2022 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-36485154

RESUMO

Growing recognition that the ovary is an end organ in sickle cell disease (SCD), advances in SCD treatment and cure, and innovations in assisted reproductive technologies invite progressive challenges in fertility care for women with SCD. The reproductive life span of women with SCD may be reduced because ovarian reserve declines more rapidly in people with SCD compared to unaffected people. Some young women have diminished ovarian reserve, a risk factor for infertility. Referrals for fertility preservation may be offered and anticipatory guidance about when to seek infertility care provided. For a subset of people with SCD, this information is also applicable when pursuing in vitro fertilization with preimplantation genetic testing to avoid implantation of an embryo with SCD. Here we explore the dimensions of SCD-related fertility care illustrated by the case of a 28-year-old woman with hemoglobin SS disease who initially presented for a hematology consultation for preconception counseling. This case highlights the complexity of preconception SCD management and care and the need to partner with patients to help align pregnancy hopes with SCD treatment and the many associated uncertainties.


Assuntos
Anemia Falciforme , Preservação da Fertilidade , Gravidez , Humanos , Feminino , Adulto , Preservação da Fertilidade/métodos , Anemia Falciforme/terapia , Anemia Falciforme/complicações , Ovário , Fatores de Risco
11.
Hematology Am Soc Hematol Educ Program ; 2022(1): 408-413, 2022 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-36485166

RESUMO

Globally, patients living with sickle cell disease are now surviving to reproductive age, with life expectancy approaching 50 years in most countries. Thus, reproductive options are now essential for patients living with the condition. However, it can be associated with maternal, delivery, and fetal complications. Outcomes may vary depending on the level of expertise and resources. In this piece we provide an optional guideline for managing sickle cell disease in pregnancy. The therapeutic option of serial exchange prophylactic transfusion has been offered in the context of a clinical trial (TAPS2).


Assuntos
Anemia Falciforme , Complicações Hematológicas na Gravidez , Gravidez , Humanos , Feminino , Pessoa de Meia-Idade , Complicações Hematológicas na Gravidez/terapia , Países Desenvolvidos , Anemia Falciforme/terapia
12.
Hematology Am Soc Hematol Educ Program ; 2022(1): 388-407, 2022 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-36485167

RESUMO

Pregnancy in women with sickle cell disease (SCD) is a life-threatening condition. In both high- and low-income countries, there is an 11-fold increased risk of maternal death and a 4-fold increased risk of perinatal death. We highlight the epidemiology of SCD-specific and obstetric complications commonly seen during pregnancy in SCD and propose definitions for acute pain and acute chest syndrome (ACS) episodes during pregnancy. We conducted a systematic review of the recent obstetric and hematology literature using full research articles published within the last 5 years that reported outcomes in pregnant women with SCD. The prevalence of acute pain episodes during pregnancy ranged between 4% and 75%. The prevalence of ACS episodes during pregnancy ranged between 4% and 13%. The estimated prevalence of pulmonary thromboembolism in women with SCD during pregnancy is approximately 0.5 to 1%. ACS is the most common cause of death and is often preceded by acute pain episodes. The most crucial time to develop these complications in pregnancy is during the third trimester and postpartum period. In a pooled analysis from studies in low- and middle-income settings, maternal death in women with SCD is approximately 2393 and 4300 deaths per 100 000 live births with and without multidisciplinary care, respectively. In comparison, in the US and northern Europe, the general maternal mortality rate is approximately 23.8 and 8 deaths per 100 000 live births, respectively. A multidisciplinary SCD obstetrics care approach reduces maternal and perinatal morbidity and mortality in low- and middle-income countries.


Assuntos
Síndrome Torácica Aguda , Dor Aguda , Anemia Falciforme , Morte Materna , Embolia Pulmonar , Feminino , Gravidez , Humanos , Síndrome Torácica Aguda/epidemiologia , Síndrome Torácica Aguda/terapia , Mortalidade Materna , Anemia Falciforme/complicações , Anemia Falciforme/terapia , Anemia Falciforme/epidemiologia , Embolia Pulmonar/complicações
14.
Hematology Am Soc Hematol Educ Program ; 2022(1): 442-449, 2022 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-36485118

RESUMO

Discussions regarding gonadal function and possible disease or treatment-related ovarian or testicular dysfunction, sexual dysfunction, and possible future infertility can be challenging in the sickle cell disease (SCD) pediatric care setting. A construct that stratifies topics into those that are time sensitive and those that require reproductive care expertise vs address gonadal health as a part of normal SCD care may be helpful. Pediatric health care discussions of gonadal function/dysfunction for patients with SCD can include (1) time-sensitive fertility consults preceding the start of gonadotoxic therapy and (2) targeted discussions at key time points during normally scheduled hematology clinic visits. The former conversations are best led by individuals with expertise in the risk for treatment-related infertility and fertility preservation. The latter discussions can be incorporated into targeted regularly scheduled visits with hematologists. These topics can be addressed as a part of planned education in pediatric care for adolescents and incorporated into transition plans as young adults transfer care to adult providers. Although the topics of puberty and gonadal health can be uncomfortable and many complex interdisciplinary and ethical issues arise in this process, these discussions can be aided by the collaterals and teaching handouts presented in this article.


Assuntos
Anemia Falciforme , Fertilidade , Adolescente , Adulto Jovem , Humanos , Criança , Anemia Falciforme/terapia , Aconselhamento
15.
Hematology Am Soc Hematol Educ Program ; 2022(1): 272-276, 2022 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-36485115

RESUMO

Treatment options for patients with sickle cell disease (SCD) continue to rapidly expand and evolve. The goal of therapies such as an allogeneic hematopoietic stem cell transplant (HSCT), gene therapy, and gene editing is to cure rather than control SCD. The benefits of these therapies must be accompanied by minimizing long-term adverse health outcomes from SCD and its treatment. SCD can have adverse effects on a variety of organ systems, including the heart, lung, kidney, and reproductive system, leading to high disease burden, morbidity, and premature mortality in both pediatric and adult patients. While curative therapies are being increasingly used, there remains a paucity of data on the long-term health outcomes associated with these treatments in children and adults with SCD. There are data available regarding the effects of HSCT performed largely for malignant diseases, from which data on SCD outcomes may be extrapolated. However, given the significant differences between these 2 populations of patients who undergo HSCT, such extrapolation is imprecise at best. Furthermore, there are currently no published data on long-term health outcomes following gene therapy for SCD due to current short follow-up times. We summarize the limited data reported on health outcomes following HSCT for SCD and emphasize the need for more research within this area.


Assuntos
Anemia Falciforme , Transplante de Células-Tronco Hematopoéticas , Adulto , Criança , Humanos , Condicionamento Pré-Transplante , Anemia Falciforme/genética , Anemia Falciforme/terapia , Transplante Homólogo , Avaliação de Resultados em Cuidados de Saúde
16.
Hematology Am Soc Hematol Educ Program ; 2022(1): 414-420, 2022 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-36485120

RESUMO

Pregnancy in women with sickle cell disease (SCD) is fraught with complications, some of which are life-threatening. Managing pregnancy in these women can be challenging, especially with poor resources, which is often the case in low-income countries. In Nigeria, for instance, up to 90% of patients pay out of pocket for medical care due to the poorly developed health insurance system, and this worsens the morbidity and mortality associated with this condition. We describe a pragmatic approach to routinely managing pregnant women with SCD in the antenatal period, showing the feasibility of effective management of these high-risk pregnancies in limited-resource settings. We also present the case of a pregnant Nigerian woman with SCD who has intrauterine growth restriction (IUGR) and acute chest syndrome (ACS), conditions that are life-threatening for the fetus and the mother, respectively, and require prompt intervention. We highlight how we successfully managed this woman in a cost-effective manner by employing relatively inexpensive tests for diagnosis and treating her effectively with oxygen, appropriate antibiotics and manual exchange blood transfusion for the ACS, and finger pulse oximeters to monitor oxygen saturation. We explore pathophysiological concepts to IUGR in women with SCD and briefly discuss the appropriate mode of delivery, including the options for pain relief in labor.


Assuntos
Síndrome Torácica Aguda , Anemia Falciforme , Complicações Hematológicas na Gravidez , Feminino , Humanos , Gravidez , Anemia Falciforme/complicações , Anemia Falciforme/terapia , Complicações Hematológicas na Gravidez/diagnóstico , Complicações Hematológicas na Gravidez/terapia , Retardo do Crescimento Fetal/terapia
17.
Hematology Am Soc Hematol Educ Program ; 2022(1): 266-271, 2022 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-36485129

RESUMO

Allogeneic hematopoietic cell transplantation, gene therapy, and gene editing offer a potential cure for sickle cell disease (SCD). Unfortunately, myelodysplastic syndrome and acute myeloid leukemia development have been higher than expected after graft rejection following nonmyeloablative conditioning and lentivirus-based gene therapy employing myeloablative busulfan for SCD. Somatic mutations discovered in 2 of 76 patients who rejected their grafts were identified at baseline at much lower levels. While a whole-genome sequencing analysis reported no difference between patients with SCD and controls, a study including whole-exome sequencing revealed a higher prevalence of clonal hematopoiesis in individuals with SCD compared with controls. Genetic risk factors for myeloid malignancy development after curative therapy for SCD are currently being explored. Once discovered, decisions could be made about whether gene therapy may be feasible vs allogeneic hematopoietic cell transplant, which results in full donor chimerism. In the meantime, care should be taken to perform a benefit/risk assessment to help patients identify the best curative approach for them. Long-term follow-up is necessary to monitor for myeloid malignancies and other adverse effects of curative therapies for SCD.


Assuntos
Anemia Falciforme , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Humanos , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/métodos , Anemia Falciforme/genética , Anemia Falciforme/terapia , Anemia Falciforme/complicações , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Doença Enxerto-Hospedeiro/etiologia
18.
Hematology Am Soc Hematol Educ Program ; 2022(1): 277-282, 2022 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-36485131

RESUMO

Curative therapies for sickle cell disease include allogeneic hematopoietic stem cell transplantation (HSCT) and gene-modified autologous stem cell transplantation. HSCT has been used for 30 years with success measured by engraftment, symptom control, graft-vs-host disease (GVHD) risk, organ toxicity, and immune reconstitution. While human leukocyte antigen-matched sibling donor (MSD) transplants have excellent outcomes, alternate donor transplants (unrelated/haploidentical) are just beginning to overcome GVHD and engraftment hurdles to match MSD. Gene therapy, a newly developed treatment, is undergoing careful evaluation in many trials with varying approaches. The risk/benefit ratio to the patient in relation to outcomes, toxicities, and mortality risk drives eligibility for curative interventions. Consequently, eligibility criteria for MSD transplants can be less stringent, especially in the young. Posttransplant outcome analysis after the "cure" with respect to organ function recovery is essential. While established damage such as stroke is irreversible, transplant can help stabilize (pulmonary function), prevent further deterioration (stroke), improve (neurocognition), and protect unaffected organs. Tracking organ functions postintervention uniformly between clinical trials and for adequate duration is essential to answer safety and efficacy questions related to curative therapies. Age-appropriate application/outcome analyses of such therapies will be the ultimate goal in overcoming this disease.


Assuntos
Anemia Falciforme , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Acidente Vascular Cerebral , Humanos , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante Homólogo , Transplante Autólogo , Doença Enxerto-Hospedeiro/prevenção & controle , Anemia Falciforme/terapia , Irmãos
19.
PLoS One ; 17(12): e0256248, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36508412

RESUMO

OBJECTIVES: To adopt the FAIR principles (Findable, Accessible, Interoperable, Reusable) to enhance data sharing, the Cure Sickle Cell Initiative (CureSCi) MetaData Catalog (MDC) was developed to make Sickle Cell Disease (SCD) study datasets more Findable by curating study metadata and making them available through an open-access web portal. METHODS: Study metadata, including study protocol, data collection forms, and data dictionaries, describe information about study patient-level data. We curated key metadata of 16 SCD studies in a three-tiered conceptual framework of category, subcategory, and data element using ontologies and controlled vocabularies to organize the study variables. We developed the CureSCi MDC by indexing study metadata to enable effective browse and search capabilities at three levels: study, Patient-Reported Outcome (PRO) Measures, and data element levels. RESULTS: The CureSCi MDC offers several browse and search tools to discover studies by study level, PRO Measures, and data elements. The "Browse Studies," "Browse Studies by PRO Measures," and "Browse Studies by Data Elements" tools allow users to identify studies through pre-defined conceptual categories. "Search by Keyword" and "Search Data Element by Concept Category" can be used separately or in combination to provide more granularity to refine the search results. This resource helps investigators find information about specific data elements across studies using public browsing/search tools, before going through data request procedures to access controlled datasets. The MDC makes SCD studies more Findable through browsing/searching study information, PRO Measures, and data elements, aiding in the reuse of existing SCD data.


Assuntos
Anemia Falciforme , Metadados , Humanos , Disseminação de Informação , Anemia Falciforme/terapia
20.
Viruses ; 14(12)2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36560719

RESUMO

We have previously demonstrated that both the original γ-globin lentiviral vector (LV) GGHI and the optimized GGHI-mB-3D LV, carrying the novel regulatory elements of the 3D HPFH-1 enhancer and the 3' ß-globin UTR, can significantly increase HbF production in thalassemic CD34+ cells and ameliorate the disease phenotype in vitro. In the present study, we investigated whether the GGHI-mB-3D vector can also exhibit an equally therapeutic effect, following the transduction of sickle cell disease (SCD) CD34+ cells at MOI 100, leading to HbF increase coupled with HbS decrease, and thus, to phenotype improvement in vitro. We show that GGHI-mB-3D LV can lead to high and potentially therapeutic HbF levels, reaching a mean 2-fold increase to a mean value of VCN/cell of 1.0 and a mean transduction efficiency of 55%. Furthermore, this increase was accompanied by a significant 1.6-fold HbS decrease, a beneficial therapeutic feature for SCD. In summary, our data demonstrate the efficacy of the optimized γ-globin lentiviral vector to improve the SCD phenotype in vitro, and highlights its potential use in future clinical SCD trials.


Assuntos
Anemia Falciforme , Talassemia beta , Humanos , gama-Globinas/genética , Terapia Genética , Hemoglobina Fetal/genética , Vetores Genéticos/genética , Lentivirus/genética , Talassemia beta/genética , Talassemia beta/terapia , Anemia Falciforme/genética , Anemia Falciforme/terapia
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