Paediatric haematopoietic stem cell transplantation research priorities: results from an international multi-stakeholder Priority Setting Partnership

Through an international, multi-stakeholder Priority Setting Partnership involving patients, families, and healthcare professionals across four countries, this study identified the top 10 research priorities for paediatric haematopoietic stem cell transplantation, highlighting key gaps in personalized medicine, immune recovery, and adjunct interventions like exercise and nutrition.

The Gist

Imagine a massive, high-stakes medical procedure called a stem cell transplant. For many children with serious blood diseases or immune problems, this is their "Hail Mary" play—their best chance at survival. It's like rebuilding a house from the ground up while the family is still living inside it.

However, this process is incredibly risky. The "construction" often comes with leaks, fires (infections), and structural failures (complications). For years, the architects (doctors) and the construction crew (researchers) have been deciding which blueprints to follow and which problems to fix first, often without asking the people actually living in the house: the children and their families.

This paper is about finally inviting everyone to the table to design the future.

Here is the story of how they did it, using simple analogies:

1. The Big Meeting (The Priority Setting Partnership)

The researchers, led by the James Lind Alliance, decided to stop guessing what matters and start asking. They organized a massive, international "town hall" meeting involving four countries: Australia, New Zealand, the Netherlands, and the UK.

They didn't just want doctors to speak; they wanted the "homeowners" (patients and parents) to have an equal voice. Think of it as a giant potluck where doctors bring their medical expertise, and families bring their lived experiences, and together they decide what the menu for the future should be.

2. Gathering the Questions (The Scoping Survey)

First, they threw open the doors and asked: "What keeps you up at night? What questions do you wish someone would answer?"

• The Result: They collected 667 different questions.
• The Mix: About half came from doctors, and half came from families.
• The Themes: The families were most worried about the scary side effects and the emotional toll. The doctors were more focused on standardizing treatments and nutrition. It was like two different groups looking at the same storm: one group was worried about the wind breaking the windows (toxicity), while the other was worried about the roof leaking (treatment protocols).

3. The Reality Check (Evidence Checking)

With 667 questions, they needed to clean up the list. They acted like librarians or detectives. They went through the library of existing medical research to see: "Has anyone already solved this?"

• They found that many questions had already been answered by science.
• They filtered out the ones that were too specific to adults or happened years after the transplant.
• The Filter: They narrowed the massive list down to 35 "True Mysteries"—questions that science still doesn't have good answers for.

4. The Vote (Interim Survey)

Next, they asked everyone to vote on these 35 mysteries. Imagine a ranking game where you can only pick your top 10 favorites.

• Doctors and families voted again.
• They found some interesting differences. For example, doctors cared a lot about a specific blood condition called "TMA," while families cared much more about keeping their kids in school and not missing out on life during the treatment.
• This voting process whittled the list down to a shortlist of 19 questions.

5. The Final Summit (The Consensus Workshop)

Finally, a group of 22 people (doctors, parents, and survivors) met for a workshop. They didn't just vote; they talked. They used a special technique to make sure everyone was heard, even the shyest voices. They debated, discussed, and eventually agreed on the Top 10 Most Important Research Questions to solve next.

The Top 10 Priorities (The "To-Do" List)

The final list is a mix of high-tech science and human care. Here is what they decided to focus on, translated into everyday language:

1. Personalized Medicine: Stop using a "one-size-fits-all" approach. Just like a tailor makes a suit that fits perfectly, we need to adjust the medicine doses for each child's specific body to reduce poison and side effects.
2. Immune System Recovery: How do we help the child's new immune system wake up faster so they don't get sick?
3. The "Gut Garden" (Microbiome): Our gut bacteria are like a garden. If the garden is messy, the immune system gets confused. We need to figure out how to keep this garden healthy to prevent complications.
4. Exercise and Nutrition: It's not just about pills; it's about building strength. We need to find the best ways to feed and exercise kids before and during the transplant so they are strong enough to survive the ordeal.
5. Mental Health: The transplant is scary. We need better ways to support the child's mind and the family's sanity, helping them cope with the stress and fear.
6. Graft-vs-Host Disease (GvHD): This is when the new cells attack the body. We need better ways to predict and stop this "friendly fire."
7. Infection Control: How do we keep kids safe from germs without locking them in a bubble forever?
8. Pain Management: How do we make the treatment less painful?
9. School and Life: How do we keep kids connected to their friends and school while they are sick?
10. Better Communication: How do doctors and families talk to each other so everyone understands what's happening?

Why This Matters

Think of medical research as a compass. Before this study, the compass was mostly pointing in the direction doctors thought was best. Now, thanks to this paper, the compass has been recalibrated. It now points in the direction that both the doctors and the families agree is the most urgent path forward.

This isn't just a list of questions; it's a roadmap. It tells funding agencies and scientists exactly where to spend their money and energy to save more lives and make the journey less scary for the children and families who need it most.

Technical Summary

1. Problem Statement

Haematopoietic stem cell transplantation (HSCT) is a curative therapy for various pediatric malignant and non-malignant conditions but carries high risks of mortality and morbidity, particularly within the first 180 days post-transplant. Complications include infection, organ failure, and Graft-versus-Host Disease (GvHD).

• The Gap: Historically, research agendas in pediatric HSCT have been driven primarily by clinicians, researchers, and government agencies, with minimal input from patients, families, or caregivers.
• The Consequence: This lack of consumer perspective has led to a misalignment between research priorities and the actual needs of patients and families. Furthermore, the volume of investigator-initiated interventional trials in this field is low, and existing research blueprints rarely incorporate meaningful patient-reported outcomes.
• The Objective: To establish the first international, shared research agenda for pediatric HSCT that integrates the perspectives of healthcare professionals (HCPs) and consumers (patients, parents, and carers) across Australia, New Zealand, the Netherlands, and the United Kingdom.

2. Methodology

The study utilized the James Lind Alliance (JLA) Priority Setting Partnership (PSP) methodology, a rigorous, evidence-based framework designed to identify and prioritize research uncertainties through consensus. The project ran from January 2024 to June 2025.

Study Scope:

• Population: Children and adolescents (or adults transplanted as children) undergoing HSCT.
• Timeframe: The first 180 days (6 months) post-transplantation.
• Indications: All HSCT indications (malignant and non-malignant).

Four-Phase Process:

1. Part 1: International Scoping Survey:
   • An open-ended online survey collected research uncertainties from HCPs and consumers.
   • Participation: 148 respondents generated 667 unique topic ideas (55% HCPs, 45% consumers).
2. Part 2: Summarising and Evidence Checking:
   • Responses were coded into 80 summary questions.
   • Evidence Verification: Information specialists conducted systematic literature reviews to determine if questions were "answered," "partially answered," or "unanswered" based on high-quality evidence (systematic reviews, guidelines, meta-analyses) published between 2020–2025.
   • Outcome: 35 questions were identified as true uncertainties (unanswered or partially answered) and advanced to the next phase.
3. Part 3: Interim Prioritisation Survey:
   • A second survey allowed 224 participants to rank the 35 uncertainties.
   • Analysis: Responses were tallied by stakeholder group (HCP vs. consumer) and country.
   • Outcome: A shortlist of 19 questions was generated based on combined scores and Steering Committee review to ensure representation of minority groups.
4. Part 4: Consensus Workshop:
   • A two-day workshop involving 22 participants (13 HCPs, 9 consumers) from the four participating countries.
   • Technique: Facilitated by JLA Advisers using the Nominal Group Technique to deliberate, rank, and reach a consensus on the final top 10 priorities.

3. Key Contributions

• First International PSP in Pediatric HSCT: This is the inaugural application of the JLA methodology specifically for pediatric HSCT on a multinational scale.
• Stakeholder Integration: It successfully bridged the gap between clinical and consumer perspectives, revealing distinct but complementary priorities. For instance, while clinicians prioritized clinical interventions like thrombotic microangiopathy (TMA) management, consumers prioritized quality-of-life issues such as maintaining schooling during treatment.
• Evidence-Based Filtering: The study rigorously filtered out questions already answered by recent high-quality evidence, ensuring the final list represents genuine knowledge gaps.
• Multidisciplinary Scope: The resulting priorities span biological, functional, and psychosocial domains, moving beyond purely survival-focused metrics to include holistic recovery.

4. Results

The process culminated in a consensus on the Top 10 Research Priorities for pediatric HSCT (first 180 days):

1. Personalized Medicine: Optimizing conditioning regimens and drug dosing (e.g., pharmacogenomics, pharmacokinetics) to reduce toxicity.
2. Immune Recovery: Strategies to accelerate and improve immune reconstitution.
3. GvHD Management: Improved prediction, prevention, and early identification of Graft-versus-Host Disease.
4. Adjunct Interventions: The role of exercise, nutrition, and physical rehabilitation in improving outcomes.
5. Microbiome Strategies: Investigating the impact of the gut microbiome on infection risk, GvHD, and immune recovery.
6. Infection Prevention: Optimizing isolation practices and prophylactic strategies.
7. Psychosocial Support: Addressing psychological distress, anxiety, and caregiver strain.
8. Neurocognitive Outcomes: Identifying risks and interventions for cognitive deficits and educational disruption.
9. Standardization: Developing standardized protocols for supportive care and treatment processes.
10. Communication: Improving communication strategies between the healthcare team, patients, and families.

Key Findings on Disparities:

• Consumers placed higher emphasis on psychosocial wellbeing, communication, and education continuity.
• HCPs placed higher emphasis on standardization of treatment, specific clinical toxicities (like TMA), and nutritional/exercise protocols.
• Toxicity and Side Effects emerged as the most dominant theme across all submissions (28.2% of total comments).

5. Significance

• Research Direction: This study provides a definitive, evidence-based roadmap for funding agencies, trial consortia, and advocacy groups to direct future investment in pediatric HSCT.
• Patient-Centered Care: By prioritizing questions co-designed with patients and families, the research agenda is more likely to address outcomes that matter most to survivors, such as quality of life, neurocognitive function, and long-term resilience.
• Clinical Translation: The priorities highlight a shift toward precision medicine (personalized dosing) and supportive care optimization (microbiome, exercise, nutrition), areas where current clinical practice often lags behind emerging science.
• Global Applicability: While the study focused on four high-income nations with similar healthcare systems, the framework and priorities offer a template for future international collaborations, including potential expansion to low-and-middle-income countries.

Limitations Noted:
The study acknowledged potential regional weighting (higher participation from Australia and the UK), the exclusion of non-English speakers, and a focus strictly on the first 6 months post-transplant, potentially missing late-effect complications. Additionally, certain specialist groups (e.g., psychologists, late-effects specialists) were under-represented in the final workshop.