Parental perspective on the risk of infertility and fertility preservation options for children and adolescents with sickle cell disease considering hematopoietic stem cell transplantation.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HCT) performed in children from human leukocyte antigen (HLA)-identical related donors is associated with very high survival rates and disease-free survival. Patients are exposed to gonadotoxic alkylating agents or irradiation in the HCT conditioning regimen. Consequently, infertility is a major long-term complication of HCT for sickle cell disease (SCD). We sought to understand how caregivers perceive the risk of infertility from HCT, how they perceive the options for fertility preservation, and how this risk perception impacted their decision-making to pursue HCT. PROCEDURES: We conducted qualitative interviews with primary caregivers after a consultation for HCT for SCD. Data were analyzed using descriptive qualitative analysis. RESULTS: We interviewed 19 primary caregivers who had attended a consultation with an HCT physician (female, age 25-59 [median 39] years). Eleven participants reported that their child had an available HLA-matched donor. Analysis revealed that (i) mothers were worried about death and graft-versus-host disease from HCT, more than about the risk of infertility; (ii) parents have a realistic understanding of the risk of infertility after HCT and take it into consideration in decision-making; (iii) parents report multiple barriers to fertility preservation. CONCLUSION: For parents actively considering HCT for their child with SCD, the risk of infertility while important was not a barrier to pursuing HCT. Inconvenience and invasiveness of fertility preservation procedures are some of the barriers to pursuing fertility preservation for their child. Future research must aim at addressing these barriers to fertility preservation.

Multimodal phenotyping and correlates of pain following hematopoietic cell transplant in children with sickle cell disease.

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.

Primary caregiver decision-making in hematopoietic cell transplantation and gene therapy for sickle cell disease.

BACKGROUND: Improved outcomes and the availability of clinical trials of hematopoietic cell transplantation (HCT) from alternate donors and genetically modified autologous hematopoietic progenitor cells have expanded the applicability of HCT for sickle cell disease (SCD). To understand the perspective of primary caregivers exploring HCT in the current milieu, we asked the research question "What motivates primary caregivers to decide to consider HCT and to seek, and to attend, an HCT consultation?" PROCEDURES: We conducted qualitative interviews with primary caregivers within one week after a consultation for HCT for SCD. Data were analyzed using open and axial coding stages of grounded theory methodology. RESULTS: We interviewed 29 primary caregivers (26 females, age 29 to 64 [median 42] years). Primary caregivers report of SCD complications in their child included at least one in the last year by 23 (82%), few or none by 8 (28%), and pain on ≥3 days a week by 13 (46%) primary caregivers. Qualitative analysis revealed that primary caregivers, (i) learn about curative options through social networks, social media, and the news media; (ii) seek consultation because of their child's diminished quality of life, recent complications, an imminent major medical decision, or anxiety about future severe complications; and (iii) see gene therapy as a new, less invasive, and more acceptable treatment. CONCLUSION: Primary caregivers of children with SCD learn about HCT through social networks, social and news media, and explore HCT as a means to prevent SCD complications and help their child live a normal life.

Patient and family experience with chronic transfusion therapy for sickle cell disease: A qualitative study.

BACKGROUND: There is a limited understanding of the patient and family experience of Chronic Transfusion Therapy (CTT) for prevention of complications of Sickle Cell Disease (SCD). We sought to understand patient and family experience with CTT using qualitative methods. METHODS: Fifteen parents of children < 18 years old and nine children 12-18 years old with SCD who were receiving CTT for > 1 year were interviewed using a semi-structured interview format, and interviews were analyzed using open coding methods. RESULTS: Four themes created a narrative of the patient and family experience of CTT: 1) Burden of CTT, 2) Coping with CTT, 3) Perceived benefits and risks of CTT, and 4) Decision making regarding CTT. Participants reported substantial burden of CTT, including the impact of CTT on daily life and family, distress about venous access, burden of chelation therapy, and anxiety about CTT complications. Participants described how they coped with CTT. Participants reported increased energy, decreased pain, fewer hospitalizations, and stroke prevention with CTT, but also recognized complications of CTT, though awareness was limited in adolescents. Parents described sharing in the informed decision-making process with their healthcare provider about CTT, but adolescent patient participants reported that they were not involved in this process. CONCLUSIONS: CTT is associated with significant patient and family burden. Support from family, healthcare providers and school may help individuals cope with some of this burden. These findings provide the basis for future studies to identify strategies to mitigate the burden of CTT and improve the patient experience with this therapy. Future studies should also systematically assess patient knowledge about the key components of CTT and chelation using quantitative assessments.

A Decision Support Tool for Allogeneic Hematopoietic Stem Cell Transplantation for Children With Sickle Cell Disease: Acceptability and Usability Study.

BACKGROUND: Individuals living with sickle cell disease (SCD) may benefit from a variety of disease-modifying therapies, including hydroxyurea, voxelotor, crizanlizumab, L-glutamine, and chronic blood transfusions. However, allogeneic hematopoietic stem cell transplantation (HCT) remains the only nonexperimental treatment with curative intent. As HCT outcomes can be influenced by the complex interaction of several risk factors, HCT can be a difficult decision for health care providers to make for their patients with SCD. OBJECTIVE: The aim of this study is to determine the acceptability and usability of a prototype decision support tool for health care providers in decision-making about HCT for SCD, together with patients and their families. METHODS: On the basis of published transplant registry data, we developed the Sickle Options Decision Support Tool for Children, which provides health care providers with personalized transplant survival and risk estimates for their patients to help them make informed decisions regarding their patients' management of SCD. To evaluate the tool for its acceptability and usability, we conducted beta tests of the tool and surveys with physicians using the Ottawa Decision Support Framework and mobile health app usability questionnaire, respectively. RESULTS: According to the mobile health app usability questionnaire survey findings, the overall usability of the tool was high (mean 6.15, SD 0.79; range 4.2-7). According to the Ottawa Decision Support Framework survey findings, acceptability of the presentation of information on the decision support tool was also high (mean 2.94, SD 0.63; range 2-4), but the acceptability regarding the amount of information was mixed (mean 2.59, SD 0.5; range 2-3). Most participants expressed that they would use the tool in their own patient consults (13/15, 87%) and suggested that the tool would ease the decision-making process regarding HCT (8/9, 89%). The 4 major emergent themes from the qualitative analysis of participant beta tests include user interface, data content, usefulness during a patient consult, and potential for a patient-focused decision aid. Most participants supported the idea of a patient-focused decision aid but recommended that it should include more background on HCT and a simplification of medical terminology. CONCLUSIONS: We report the development, acceptability, and usability of a prototype decision support tool app to provide individualized risk and survival estimates to patients interested in HCT in a patient consultation setting. We propose to finalize the tool by validating predictive analytics using a large data set of patients with SCD who have undergone HCT. Such a tool may be useful in promoting physician-patient collaboration in making shared decisions regarding HCT for SCD. Further incorporation of patient-specific measures, including the HCT comorbidity index and the quality of life after transplant, may improve the applicability of the decision support tool in a health care setting.

Assessment of Patient and Caregiver Attitudes and Approaches to Decision-Making Regarding Bone Marrow Transplant for Sickle Cell Disease: A Qualitative Study.

Importance: Bone marrow transplant (BMT) is a potentially curative treatment for sickle cell disease (SCD). Patient and caregiver attitudes toward BMT for SCD and the willingness to accept risks of BMT vary, but these attitudes are not well understood. Objective: To understand patient and caregiver perceptions of and attitudes toward BMT for SCD and decision-making about BMT. Design, Setting, and Participants: Qualitative study of interview transcripts from a convenience sample. Transcripts were from adults with SCD and caregivers of patients with SCD recruited from national and regional SCD conferences, symposia, and sickle cell clinics in 2 cities. Interview transcripts were used from the needs assessment phase to develop a patient-decision aid in 2013 to 2014 (group 1) and from the baseline point in 2015 to 2016 (group 2) of the parent trial, a randomized clinical trial of adults and caregivers of patients with SCD to evaluate the effectiveness of a patient decision aid. Main Outcomes and Measures: Participant perspectives on decision-making regarding BMT for SCD. Results: Fifty-seven transcripts from adults with SCD and 50 transcripts from caregivers of patients with SCD were included. Median (interquartile range [IQR]) age of adults with SCD was 34 (21-50) years in group 1 and 30 (23-38) years in group 2. The median (IQR) age of caregivers was 42.5 (31-52) years in group 1 and 41 (35-46.5) years in group 2. Most transcripts from adults with SCD (75.0% in group 1 and 72.4% in group 2) and caregivers of patients with SCD (76.7% in group 1 and 85.0% in group 2) were from female participants. Bone marrow transplant was perceived as a treatment option associated with serious risks. Reported attitudes toward BMT occurred on a continuum ranging from unfavorable to favorable. Participants reported serious decisional dilemma regarding BMT for SCD. Most participants expressed interest in learning about BMT or curative treatments. Conclusions and Relevance: This qualitative study found a continuum in attitudes toward BMT for SCD and highlights the complexity of decision-making in BMT for SCD. Patients and families with SCD expressed an interest in learning about BMT. Future prospective studies of patient decision-making regarding BMT, especially in the context of emerging curative and novel disease-modifying therapies for SCD, are warranted.

Management of Chronic Pain in Adults Living With Sickle Cell Disease in the Era of the Opioid Epidemic: A Qualitative Study.

Importance: The hallmark of sickle cell disease (SCD) is vaso-occlusive pain that may be acute and episodic or may progress to chronic, persistent pain with unpredictable and disabling exacerbations. Patients with SCD rely on opioids almost exclusively for acute and chronic pain management. Objective: To understand how the current opioid epidemic and subsequent guidelines from the Centers for Disease Control and Prevention are associated with the management of acute and chronic pain for patients with SCD. Design, Setting, and Participants: Qualitative study using semistructured interview guides. Interviews 1 hour or longer were conducted over the telephone. Participants were adults (aged ≥18 years) diagnosed with SCD who experienced pain on 3 or more days per week recruited from national SCD conferences, symposiums, and 2 sickle cell clinics. Open coding analysis facilitated thematic analysis of interview transcripts. Data collection took place from May 2017 to June 2018. Main Outcomes and Measures: Participant perspective of any changes to their pain management associated with the 2016 guidelines from the Centers for Disease Control and Prevention. Results: The 15 adults interviewed had a median (range) age of 32 (21-52) years; 13 (87%) were female; and all were of African American race/ethnicity. Participants reported that recently their opioid prescriptions had become more restrictive, were more closely monitored, and were increasingly difficult to fill in pharmacies. Participants also described increased stigmatization about opioid use and that their medical care was being affected by the physician's exclusive focus on reducing pain medication use. There was an emerging interest among adult patients in the consideration of the use of alternative therapies, including marijuana, to manage pain. Conclusions and Relevance: These findings suggest that from the perspective of adults living with SCD, the opioid epidemic may have negatively affected patients' care by increasing barriers to opioids. Patients reported decreased opioid dosing, increased stigmatization regarding opioid use, physician preoccupation with opioid dosage interfering with comprehensive care, and lack of access to alternative therapies.

From trust to skepticism: An in-depth analysis across age groups of adults with sickle cell disease on their perspectives regarding hydroxyurea.

Despite its efficacy, the uptake of HU in adults with sickle cell disease (SCD) is poor likely due to a combination of system, provider, and patient-related factors. We investigated attitudes of adult patients towards HU by conducting qualitative interviews with 95 adult SCD patients (age 18 to 67 years old, 71 were female). While 53% of all participants reported that they were currently taking HU, patients ranging in age 18-30 years (Group 1) were more likely to report current HU use as compared to those (Group 2) ranging in age 31-67 years (65% vs. 41% P = 0.01). Most Group 1 participants who reported currently taking HU indicated that the decision to start HU was made by a parent, though some made the decision themselves as a young adult. Group 1 participants expressed trust in the efficacy of HU as well as trust that their physician adequately shared risks and benefits for the medication. The Group 2 participants, who were not currently on HU, were skeptical that all the risks and benefits of HU were known, were concerned that the efficacy of HU was not proven, and that they were not receiving complete information about its potential side effects. Of Group 2 participants who reported currently being on HU, 25% were concerned about the side effects and efficacy of HU and reported continuing HU because of a lack of effective alternatives. These data suggest that there are significant differences by age in adult SCD patients' attitudes towards, utilization and understanding of the risks and benefits of HU.

Proponent or collaborative: Physician perspectives and approaches to disease modifying therapies in sickle cell disease.

Sickle cell disease (SCD) is an inherited blood disorder that primarily affects African-American and other ethnic minority populations. There are three available disease-modifying therapies for sickle cell disease: hydroxyurea (HU), bone marrow transplantation (BMT), and chronic blood transfusion (CBT). Since these treatments vary in their therapeutic intent, efficacy in preventing progression of the disease, short and long-term adverse effects, costs and patient burden, the decision-making process regarding these therapies is complicated for both the patient and healthcare provider. While previous research has focused on the patient perspective of treatment-related decision making, there is a paucity of research investigating the physician perspective of treatment-related decision making. We conducted a qualitative study with physicians who were experts in the field of SCD. Interviews focused on physician perceptions of patient decisional needs as well as physicians' approach to decision making regarding disease-modifying therapies in SCD. Thirty-six physician interviews were analyzed, with a focus on their perspectives regarding available treatment options and on how they approach decision making with patients. We identified two narrative approaches. The Collaborative approach (CA) was characterized by emphasizing the need to discuss all possible treatment options to ensure that the patient and/or family was equipped to make an informed decision. The Proponent approach (PA) was characterized by strongly advocating a pre-determined treatment plan and providing patients/families with information, with the objective of convincing them to accept the treatment. An interplay of patient-related and disease-related factors, decision type and physician-related factors, as well as institutional frameworks, influenced physician perspectives on treatment options and decision making regarding these therapies. These findings point to the potential value of developing systems to foster patient engagement as a way of facilitating shared decision making.