Asunto(s)
Anemia de Células Falciformes , Actitud del Personal de Salud , Actitud Frente a la Salud , Terapia Genética , Anemia de Células Falciformes/genética , Anemia de Células Falciformes/psicología , Anemia de Células Falciformes/terapia , Terapia Genética/métodos , Terapia Genética/psicología , Humanos , Pacientes/psicología , Médicos/psicologíaRESUMEN
Importance: The introduction of gene therapies into the clinical care landscape for individuals living with sickle cell disease (SCD) represents a momentous achievement with the potential to rewrite the story of the world's most prevalent heritable blood disorder. This disease, which was first described in 1910 and did not see a US Food and Drug Administration-approved therapeutic until 1998, is poised to be among the first to realize the promise of gene therapy and genome editing. However, the future of these treatments now rests on how evidence of safety, outcomes, and acceptance in clinical practice unfolds in SCD. Furthermore, historic injustices involving the exploitation of individuals from minoritized racial and ethnic groups in medical contexts necessitate extreme care in ensuring readiness among individuals with SCD considering genetic therapies. Objective: To address a gap in resources focused on patient readiness for gene therapy. Evidence Review: The Cure Sickle Cell Initiative organized the Patient Readiness and Resilience Working Group in September 2020. Membership was comprised of behavioral health clinicians and scientists with expertise in SCD, adults with lived experience with SCD, and a caregiver. Over 2 years, the working group developed consensus recommendations and created resources to guide implementation of pregene therapy patient readiness assessments. Recommendations centered on strategies to enhance delivery of education about gene therapy and assess knowledge and understanding, interest and motivation, and psychosocial risk and resilience factors. Findings: Five goals of a pregene therapy patient readiness assessment were identified: (1) gathering information about a patient's understanding of and perceived readiness for gene therapy; (2) encouraging an open dialogue; (3) providing a conceptualization of psychosocial factors that may influence participation in gene therapy; (4) identifying patient strengths that can be used to promote psychosocial well-being before, during, and after gene therapy; (5) identifying and addressing psychosocial risks. Conclusions and Relevance: Patient readiness and psychosocial factors will have tangible implications for the success of gene therapy at individual and collective levels. Health care institutions, industry, payers, policymakers, and clinicians all shoulder responsibility for ensuring that patients with SCD are adequately prepared for gene therapy and supported in ways that optimize readiness and access. Resources described here may be leveraged as a guide to support implementation of pregene therapy assessments of patient readiness and resilience in SCD.
Asunto(s)
Anemia de Células Falciformes , Terapia Genética , Resiliencia Psicológica , Humanos , Anemia de Células Falciformes/terapia , Anemia de Células Falciformes/genética , Anemia de Células Falciformes/psicología , Consenso , Adulto , Femenino , Masculino , Medición de RiesgoRESUMEN
Assisted reproductive technologies (ART) are not yet systematically available to people with sickle cell disease or their parents. Fertility care for these groups requires addressing sickle cell disease-associated infertility risks, fertility preservation options, pregnancy possibilities and outcomes, and, when needed, infertility treatment. People with a chance of having a child with sickle cell disease can use in-vitro fertilisation with preimplantation genetic testing to conceive a child unaffected by sickle cell disease. Also, parents of children with sickle cell disease can use this technology to identify embryos to become potential future matched sibling donors for stem cell transplant. In the USA, disparities in fertility care for the sickle cell disease community are especially stark. Universal screening of newborn babies' identifies sickle cell disease and sickle cell trait, guidelines direct preconception genetic carrier screening, and standard-of-care fertility preserving options exist. However, potentially transformative treatments and cures for patients with sickle cell disease are not used due to iatrogenic infertility concerns. In diversely resourced care settings, obstacles to providing fertility care to people affected by sickle cell disease persist. In this Viewpoint, we contend that fertility care should be incorporated into the comprehensive care model for sickle cell disease, supporting alignment of treatment goals with reproductive life plans and delivering on the promise of individualised high-quality care for people with sickle cell disease and their families. We consider the obligation to provide fertility care in light of medical evidence, with acknowledgment of formidable obstacles to optimising care, and powerful historical and ethical considerations.
Asunto(s)
Anemia de Células Falciformes , Preservación de la Fertilidad , Infertilidad , Embarazo , Femenino , Recién Nacido , Lactante , Niño , Humanos , Fertilidad , Pruebas Genéticas , Infertilidad/genética , Anemia de Células Falciformes/genéticaRESUMEN
BACKGROUND: Sickle cell disease (SCD) is a life-limiting inherited hemoglobinopathy that results in significant complications and affects quality of life. Hematopoietic stem cell transplantation (HSCT) is currently the only curative intervention for SCD; however, guidelines are needed to inform how to apply HSCT in clinical practice. OBJECTIVE: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and health professionals in their decisions about HSCT for SCD. METHODS: The multidisciplinary guideline panel formed by ASH included 2 patient representatives and was balanced to minimize potential bias from conflicts of interest. The Mayo Evidence-Based Practice Research Program supported the guideline development process, including performing systematic evidence reviews (through 2019). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE Evidence-to-Decision frameworks, to assess evidence and make recommendations, which were subject to public comment. RESULTS: The panel agreed on 8 recommendations to help patients and providers assess how individuals with SCD should consider the timing and type of HSCT. CONCLUSIONS: The evidence review yielded no randomized controlled clinical trials for HSCT in SCD; therefore, all recommendations are based on very low certainty in the evidence. Key recommendations include considering HSCT for those with neurologic injury or recurrent acute chest syndrome at an early age and to improve nonmyeloablative regimens. Future research should include the development of a robust SCD registry to serve as a comparator for HSCT studies.
Asunto(s)
Anemia de Células Falciformes , Hematología , Trasplante de Células Madre Hematopoyéticas , Anemia de Células Falciformes/terapia , Humanos , Calidad de Vida , Trasplante de Células Madre , Estados UnidosRESUMEN
BACKGROUND: Donors other than matched siblings and low-intensity conditioning regimens are increasingly used in haematopoietic stem cell transplantation. We aimed to compare the relative risk of donor type and conditioning regimen intensity on the transplantation outcomes of in patients with sickle cell disease. METHODS: For this retrospective cohort study, we collected data from 90 US centres reported to the Center for International Blood and Marrow Transplant Research. Eligible patients were younger than 50 years, had genetically confirmed sickle cell disease (Hb SS) or sickle beta thalassemia (Hb Sß), and underwent allogeneic haematopoietic cell transplantation between Jan 15, 2008, and Dec 28, 2017. We considered transplants from donor-recipient pairs matched at the allele-level (HLA-A, HLA-B, HLA-C, and HLA-DRB1), including HLA-matched sibling donors, haploidentical related donors, matched unrelated donors, or mismatched unrelated donors. The main outcome was event-free survival. The effect of donor type, conditioning regimen intensity (myeloablative, non-myeloablative, and reduced-intensity regimens), age (≤12 or 13-49 years), sex, performance score, comorbidity index, recipient cytomegalovirus serostatus, graft type (bone marrow, peripheral blood, or umbilical cord blood), and transplantation period (2008-12 and 2013-17) on outcomes was studied using Cox regression models. FINDINGS: Of 996 patients with sickle cell disease and who underwent transplantation in 2008-17, 910 (91%) were included (558 [61%] patients had HLA-matched sibling donors, 137 [15%] haploidentical related donors, 111 [12%] matched unrelated donors, and 104 [11%] mismatched unrelated donors). The median follow-up was 36 months (IQR 18-60) after transplantation from HLA-matched siblings, 25 months (12-48) after transplantation from haploidentical related donors, 37 months (23-60) after transplantation from HLA-matched unrelated donors, and 47 months (24-72) after transplantation from mismatched unrelated donors. Event-free survival was worse in recipients aged 13 years or older than in those younger than 13 years (hazard ratio 1·74, 95% CI 1·24-2·45; p=0·0014) and in those who received a transplant from haploidentical related donors (5·30, 3·17-8·86; p<0·0001), matched unrelated donors (3·71, 2·39-5·75; p<0·0001), and mismatched unrelated donors (4·34, 2·58-7·32; p<0·0001) than in patients who received a transplant from matched siblings. There was no significant difference in event-free survival between recipients of transplants from non-sibling donors: haploidentical related donors (1·43, 0·81-2·50; p=0·21) or mismatched unrelated donors (1·17, 0·67-2·05; p=0·58) versus HLA-matched unrelated donors, or mismatched unrelated donors versus haploidentical related donors (1·22, 0·65-2·27; p=0·98). Event-free survival was also worse in patients conditioned with reduced-intensity regimens (1·97, 1·15-3·36; p=0·013) than in those conditioned with non-myeloablative regimens, but did not differ between those who received myeloablative compared with non-myeloablative regimens (1·57, 0·95-2·61; p=0·079). Interpretation Our data suggest that event-free survival is improved in patients with sickle cell disease who receive an allogenic transplantation at age 12 years or younger and those with an HLA-matched sibling donor. For patients without a matched sibling available for transplantation, our data do not favour one alternative donor type over another in this setting. FUNDING: National Institutes of Health and US Health Services Research Administration, Department of Health and Human Services.