Decision-making about gene therapy in transfusion dependent thalassemia

• Type of Material: Article
• Authors: Maa-Ohui Quarmyne, Emory University; Diana Ross, Emory University; Cynthia Sinha, Emory University; Nitya Bakshi, Emory University; Jeanne Boudreaux, Emory University; Lakshmanan Krishnamurti, Emory University
• Language: English
• Date: 2022-09-09
• Publisher: BMC
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2022
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s12887-022-03598-3
• Title of Journal or Parent Work: BMC PEDIATRICS
• Volume: 22
• Issue: 1
• Start Page: 536
• End Page: 536
• Grant/Funding Information: This work was supported by the Cooley’s Anemia Foundation to MOQ and the Aflac Cancer and Blood Disorders Institute. NB received funding from the National Heart, Lung and Blood Institute of the National Institutes of Health under award number 1K23HL140142. None of the funding sources had any role in design of the study and collection, analysis, and interpretation of data and in writing the manuscript.
• Keywords: QUALITATIVE RESEARCH; Life Sciences & Biomedicine; Decision-making; Science & Technology; HEMOGLOBIN; Pediatrics; INTERVIEWS; Transfusion dependent thalassemia; Gene therapy; STEM-CELL TRANSPLANTATION; SATURATION; Qualitative
• Research Categories: Health Sciences, Oncology

Abstract

Background: Hematopoietic stem cell transplantation (HSCT) is a treatment option with curative intent for patients with transfusion dependent thalassemia (TDT) but its application is limited by the lack of suitable donors and acceptability due to the related morbidity/mortality. Transplantation of autologous genetically modified hematopoietic cells, gene therapy (GT) is emerging as a promising treatment option for TDT as it eliminates graft versus host disease (GVHD) and need for immunosuppression. Early results of GT suggest that many, but not all patients achieve transfusion independence after the procedure. There is little information about the acceptability of GT in patients with TDT. We sought to examine patient/family knowledge about GT in TDT and to examine factors that influence decision-making about this therapy. Methods: Parents of children with TDT and adults with TDT were who provided informed consent underwent semi-structured interviews to understand patient/family knowledge and decision-making regarding GT in TDT. Transcribed interviews were coded and the data was examined for emerging themes using a combination of thematic and content analysis. Results: Twenty-five study participants with mean age of 38Y (17—52Y) including eight adults living with TDT, and 17 parents of children with TDT underwent semi-structured qualitative interviews. Participant responses coalesced around broad themes related to knowledge of GT, motivating/deterring factors and outcomes. Study participants expressed a desire for ‘cure’ from thalassemia including transfusion independence, chelation reduction and improved quality of life as motivators for considering GT. Insufficient knowledge about the process, long-term outcomes, safety, and side effects as well as the potential for death/failure of the procedure were deterrents for the consideration GT. Reduction in frequency of transfusions, even without elimination of transfusions was an acceptable outcome of GT for most participants. Participant choice for preferred treatment modality was split between indefinitely continuing transfusions which was familiar to them versus GT which was unfamiliar, and with an uncertain outcome. None of the participants had a matched sibling donor; alternate donor HSCT was the least preferred option in this group. Conclusion: There is tempered excitement about GT in patients/families with TDT with a general willingness to accept transfusions reduction as the outcome.