Exploring the long‐term psychosocial impact of paediatric haematopoietic stem cell transplantation for nonmalignant diseases

Abstract Introduction An understanding of the long‐term psychosocial impact of paediatric haematopoietic stem cell transplantation (HSCT) for nonmalignant diseases is needed to optimize pre‐HSCT counselling, supportive care and long‐term follow‐up programmes after HSCT for this group of patients and caregivers. Methods This qualitative study included 14 patients who underwent transplantation for a nonmalignant disease during childhood. In‐depth interviews were held online to explore patients' perspectives on the long‐term psychosocial impact of HSCT on their lives. The results were analysed based on the Grounded Theory approach. Results Patients' median age at the time of the interview was 19 years (range: 14–49), and the median years after HSCT was 12 years (range: 3–33). Four main themes were identified: (1) doing okay, (2) experiencing persistent involvement with healthcare services, (3) influence on relationships with loved ones and (4) impact on the patient's life course. Subthemes extracted were doing okay, feeling of being cured, health limitations, sense of vulnerability, ongoing connection to the hospital, acceptance, friendship, family relations, development of own identity, not taking life for granted, social development, impact on (school) career and thinking about the future. Conclusions Patients reported active coping strategies and resilience after this high‐impact treatment. The data highlight the need for patient‐adjusted supportive care, indicating more need for supportive care in the long‐term outpatient clinic. Patient Contribution This study included patients as participants. Caregivers were approached if patients were below a certain age. Additionally, preliminary results were presented during a patient conference day.


| INTRODUCTION
Paediatric allogeneic haematopoietic stem cell transplantation (HSCT) is a curative treatment option for various malignant and nonmalignant diseases. 1 The list of indications for paediatric HSCT for nonmalignant diseases is increasing and is commonly divided into three categories: haematologic (e.g., severe aplastic anaemia, sickle cell disease), metabolic (e.g., Hurler's disease) or immunological (e.g., severe combined immunodeficiency) diseases. 2 Some of these diseases are life-threatening; others are life shortening and decrease quality of life. Due to ongoing advances in HSCT procedures and concomitant improvements in survival, the long-term physical and psychosocial outcomes of HSCT are becoming increasingly important. 3,4 While the psychosocial outcomes of HSCT for malignant indications have been characterized, data are scarce for patients with a nonmalignant disease. [5][6][7][8] The most frequently described long-term psychosocial effects of HSCT for childhood cancer are anxiety, depression, posttraumatic stress reactions and behavioural and social problems. Both mental and physical late effects are likely to have a negative impact on patients' quality of life. 5,7,[9][10][11] Many children with nonmalignant diseases have already been coping with morbidity and chronic disease in the years before HSCT, often resulting in impaired quality of life. 12,13 HSCT is generally well known as a curative treatment for malignant diseases; this does not, however, apply to nonmalignant diseases, resulting in lack of peer support for these patients. There are no separate patients' associations for HSCT patients with nonmalignant diseases, as there are for patients with paediatric cancer.
A better understanding of the long-term psychosocial impact of undergoing paediatric HSCT for nonmalignant diseases is needed to optimize pre-HSCT counselling, supportive care and long-term follow-up programmes after HSCT for this group of patients. In this study, we explored patients' perspectives on the long-term psychosocial impact of HSCT on their lives.

| Study design and participants
A qualitative descriptive design was used to determine patients' perspectives on the long-term psychosocial impact of HSCT on their lives. In-depth interviews were held by videoconference, due to COVID-19 restrictions, from April to May 2021. Patients were interviewed one-on-one, and invited to be accompanied by their caregivers if they preferred. Companions were instructed to interfere as little as possible. The researcher conducted the interview using a topic guide consisting of open questions (Supporting Information: Table S1). All interviews were video-recorded and transcribed verbatim. Field notes were taken about the researchers' reflections on the interview themes. Data collection continued until data saturation was reached, which was defined as no new findings emerging in the analysis of the three latest consecutive interviews.

| Data analysis
Interviews were thematically analysed to find common patterns using the comprehensive 10-step method of the Qualitative Analysis Guide of Leuven (Supporting Information: Table S2), which is based on the Grounded Theory associated with Charmaz. 14-21 The whole process consisted of constant comparison and continuous checking of the interview data. Each transcript was analysed by two independent researchers. The researcher who conducted the interviews was a permanent part of the data collection and analysis process. The other researchers on the team (J. B., A. h. P., A. d. P.) alternated in the role of second coder and analyser of the transcripts. Each step was first performed by the researchers individually, after which they came together to compare their findings and discuss discrepancies until a consensus was reached about key storylines, coding fragments, categorizing concepts and interpreting the data. Data collection and analysis took place parallel to each other. Final coding was entered BENSE ET AL. | 2463 into the qualitative data analysis software ATLAS.ti (version 8). 22 In addition, the COREQ checklist for qualitative studies was used for explicit and comprehensive reporting (Supporting Information: Table S3). 23

| RESULTS
Eighteen participants were approached, and fourteen participants were willing to participate, with an equal gender distribution. Ages ranged from 14 to 49 years, and the interview took place at a median of 12 years (range: 3-33) after HSCT. Six participants were long term (2-10 years) after HSCT, and eight were very long term (>10 years) after HSCT. Indications for HSCT were inborn errors of immunity (n = 4), haemoglobinopathies (n = 4) or bone-marrow failures (n = 6) ( Table 1). The median interview duration was 35 min (range: 27-57).

| Doing okay
Almost all participants reported that they were 'doing okay' in their daily life. The participants were able to live the life they wanted and were feeling good. Many participants experienced late effects or needed medical treatment at the time of the interview. At the same time, the participants reported hardly any inconvenience in daily life from the disease and transplantation-related late effects.

| Feeling of being cured
The participants were positive about their recovery after HSCT.
However, some participants mentioned that the recovery took a long time, and that they had experienced some setbacks (e.g., slow immune reconstitution, sequelae of graft-vs.-host disease). The majority of the participants reported considering themselves as cured from the original disease, and had been able to leave the HSCT procedure behind them at some point.

| Health limitations
The participants reported limitations in daily life due to late effects/ complications of the HSCT. Multiple late effects were reported, such as loss of fertility, alopecia, skin abnormalities or growth abnormalities. Fatigue was one of the most frequently experienced side effects, mainly during the first few years after transplantation. All participants experienced physical, social and emotional limitations due to the side effects. As a consequence, some participants reported limitations in daily activities and needed medical care. In addition, the participants indicated that they had needed to make adjustments in daily life, and had had to learn and rebuild life skills after the transplantation (e.g., rebuilding physical health, and only gradually returning to school).

| Sense of vulnerability
The participants reported feeling more susceptible to health issues

| Acceptance
The participants indicated having a degree of acceptance on various aspects related to HSCT. The participants got used to the regular check-ups and examinations at the hospital, and some stated that it helped them to feel more certain about their physical status.
Additionally, the participants reported accepting the side effects. A few participants reported feeling unique because of the side effects.
Lastly, the participants accepted that they had received a transplantation and felt relieved from the burden of the original disease. The participants accepted the HSCT as part of themselves and of their lives.

| Friends
For most participants, the HSCT did not affect current friendships.  This study has a number of strengths. First, purposeful sampling of participants allowed to obtain a diverse study population, and there was a wide age range at the time of the interview and years Family relations ♀ 16 'They're the best parents I could wish for. When I need their help, they're always there for me. They always support me with everything'.
♂ 28 'But my mother is always concerned. She has always said "take care of yourself" or "no, don't go" or "don't do it, just stay home"'.