Design

The study is a cross-sectional and longitudinal cohort study based on questionnaire data that will be collected in 2021 as part of a long-term follow-up of a cohort consisting of adult survivors of paediatric ALL, established in 2012. Analysis of baseline data from the cohort established in 2012 has shown significant differences in comparison to norm values. Survivors of paediatric ALL estimated a lower vitality (56.9±2.9) than the norm (68.8±1.1), and a lower mental health (71.3±2.6) than the norm (80.9±0.9).14 At the planned follow-up in 2021, participants will be around 37 years old, and will have reached an age where they are expected to take responsibility for work and their own family. Therefore, in order to get an idea of the long-term effects of paediatric ALL, it is important to follow the group during this time when they are increasingly exposed to external risk factors, and when they have reached an age which in itself entails an increased risk of ill health. The data collection in 2021 will also include a cross-sectional study of adult survivors of paediatric ALL treated 1985–2007 and explorative interviews with a selection of participants.

Participants

All participants included in the data collection in 2012 will be invited to participate in the follow-up study. All individuals registered in the Swedish Childhood Cancer quality registry in 2012, diagnosed with ALL between 1985 and 1997, were eligible for inclusion (n=416). In 42 cases, the presence of mental health disorders or disabilities (downs syndrome), emigration or longer stays abroad was confided by relatives and prevented their participation. Out of the remaining 374 individuals 224 (60%) completed the questionnaire after up to two reminders. In this follow-up of the 2012 data collection, additional participants will be recruited from the same registry among those diagnosed between 1998 and 2007 (n=601). In total, the cohort, through the new recruitment, will cover people who survived paediatric ALL, diagnosed between 1985 and 2007, at an age between 0 and 15 years. The follow-up of data collected in 2012 opens up for investigating how time (chronologically) influences health outcomes in these groups.

Data collection

Data will be collected with a questionnaire and interviews from March to December 2021. The questionnaire will be based on the variables used in 2012 which included validated instruments for HRQOL (SF-36)15 and a number of variables with potential influence on HRQOL, such as sociodemographics (family, education, employment, income), life style (physical activity, sleep, alcohol and tobacco), general self-efficasy (General Self-Efficasy Scale),16 17 social support (Social Support-13),18 resilience (Resilience Scale),19 20 sense of coherence (Sense of Coherence scale),21 mental health (Depression Anxiety Stress Scale 21),22 physical health (Charlson Comorbidity Index),23 musculoskeletal pain (prevalence),24 fatigue (Multidimensional Fatigue Inventory-20),25 and sick leave and health consumption (based on self-report and national registry data). The questionnaire will be digital and invitations to participate with the link to the digital questionnaire and informed consent forms will be sent out by ordinary mail. Reminders will be sent out with 2-week intervals and with the second reminder, a paper version of the questionnaire will be sent along and will be followed by final reminder. Data collection will end 2 weeks after the final reminder and thereby close the 2-month data collection period. This process, combining a digital questionnaire, several reminders and a final reminder with a paper version of the questionnaire, will increase the probability of getting as high a response rate as possible by inviting to participate both digitally and on paper and also reduce missing data both in terms of participants failing to answer all questions in the questionnaire and dropouts of participants. To supplement the self-report data several objective clinical parameters for the participants will be collected from the Swedish Childhood Cancer quality registry, such as the treatment protocol used, risk classification, chemotherapy, radiation, bone-marrow transplantation, relapse, secondary malignancy. On submission of the questionnaire, there will also be an invitation to participate in a semistructured telephone interview (n=40) performed by a researcher who is experienced in qualitative methodology and interviews with informants in sensitive contexts (SA). In order to obtain a maximum variety of experiences, the selection of participants for the interviews will be made strategically, based on the responses from the questionnaire. This means that the selection will be made by participants being deliberately selected to achieve variation regarding, for example, intensity of treatment, gender, age, work experience and experience of HRQOL. The interviews have an exploratory approach with open-ended questions. The interview guide begins with a question about the informant’s experiences of being treated for leukaemia as a child. This is followed by questions related to health, quality of life and lifestyle, where the informants are allowed to describe what it means to them, how it is for them today and how it has been affected by having been treated for leukaemia as a child. Finally, the recommendations that the informant would like to give to healthcare professionals who currently care for children with leukaemia are touched on. In order to gain an increased understanding of what the informants express, follow-up questions will be asked, such as: Can you describe it in a little more detail? How do you mean?

Analysis

Data analysis will be carried out during the end of 2021 to end of 2022. Quantitative data will be analysed using different statistical methods depending on the research questions to be answered. In a first step, HRQOL will be described by presenting mean values and SD. The aspect of changes in HRQOL during adulthood will be investigated by using data from the cohort providing data in 2012 and 2021. For analyses when investigating the association between time for treatment and HRQOL, a comparison and test for difference in mean HRQOL between the two groups (one entering the study in 2012, the other group entering the study in 2021) will be made. When investigating factors of importance for HRQOL univariate and multiple regression analyses will be used. The size of the study population and an assumed response rate of 60%–70% should allow for a sample size sufficient for evaluations of small differences in HRQOL outcomes between groups, using the SF-36 instrument.26

The qualitative interviews will be analysed according to phenomenographic methodology as it allows to focus on how the informants perceive a certain phenomenon or aspect of the world. In the analysis, attention is directed to ‘how’ the phenomenon is perceived and describing the variation in perceptions.27 The analysis will be performed by two experienced researchers in qualitative methodology (SA and MO). After transcription, each interview will be listened to and transcripts read several times for familiarisation and to get an overall impression of the data material. Each interview will be processed by searching for statements that correspond to the purpose of the study (condensation), which will then be analysed to find similarities and differences (comparison). The condensed statements will then be grouped based on their characteristic features (grouping) and similarities between the groups will be described (articulation) and then referred to as categories (labelling). The final step in the analysis is to compare the different categories in terms of similarities and differences to ensure that the categories has unique characteristics and are on the same level of description (contrasting). Throughout the analysis, there is a constant interaction between the different stages and continuous discussion and confirmation of the process and developed results between the researchers performing the analysis and the rest of the research team. The team include a broad range of competence backgrounds both in qualitative research methodology and the clinical context and research field.

The patient and public involvement

The cohort was initially established based on interaction with children with ALL and their parents as well as with healthcare practitioners involved in the medical and social care of patients with paediatric ALL and with a local patient organisation for this group of patients. This interaction took place within the boundaries of a research-based design project aiming to develop social suppport for young survivors of ALL. It demonstrated the need to monitor long-term HRQOL and specific influencing factors within this target group. The establishment of the cohort took place in consultation with clinicians at a regional paediatric cancer centre and the Swedish Childhood Cancer Registry. There is and will continue to be target group influence over the data created in the cohort since; (1) the collected variables are based on HRQOL issues established in interaction with the target group and relevant stakeholders and (2) as data in the cohort are based on the participants’ self-reported experiences.

Ethics and dissemination

The study will be carried out in accordance with the ethics permit obtained from the Swedish ethics review authority (Dnr 2019-05181), All collected data will be treated confidentially and the participants will not be able to be identified due to coding of all data material. The results in the study will only be presented at group level without the possibility of identifying individuals. Participation in the study is voluntary and based on informed consent. Each participant will be able to withdraw their participation at any time without having to justify why. The project will contribute to development of knowledge that is of benefit to a group with increased risk of HRQOL problems later in life and investigating such risks can contribute to improving care both to children who are currently undergoing treatment for ALL and to children and adults who have undergone treatment earlier in life. Dissemination of study results will take place through reports to the national patient organisation for this target group, the national network for consultancy nurses for this target group and to the working group for the Swedish national long-term care programme for childhood cancer. Results will also reach practical application within the follow-up clinic for adults after childhood cancer at Sahlgrenska Hospital in Gothenburg.