Multisite Randomized Trial of Inpatient Palliative Care in Hematopoietic Stem Cell Transplantation: Enhancing Patient and Caregiver Outcomes

Highlights

• Inpatient palliative care (PC) integrated with hematopoietic stem cell transplantation (HSCT) significantly improves patient quality of life (QOL) at the critical nadir period during hospitalization.
• PC decreases depression and post-traumatic stress disorder (PTSD) symptoms in HSCT recipients, with sustained reductions in PTSD up to six months post-transplant.
• Caregiver-focused interventions, including meaning-centered psychotherapy, show feasibility and acceptability, addressing caregiver existential distress and psychosocial burden.
• Intervention mechanisms involve enhanced symptom management, coping support, and education rather than solely medication differences, underscoring the holistic approach of PC.

Background

Hematopoietic stem cell transplantation (HSCT) is a potentially curative but physically and psychologically taxing treatment for hematologic malignancies. Patients endure aggressive conditioning regimens leading to symptom burden such as mucositis, pain, fatigue, and psychological distress including depression, anxiety, and PTSD. Caregivers also face significant emotional and existential challenges witnessing this process. Traditionally, HSCT care has focused on disease management with limited integration of palliative approaches aimed at symptom alleviation and psychosocial support. Emerging evidence suggests early and integrated palliative care may mitigate these burdens and improve outcomes.

Key Content

Chronological Development of Evidence for Palliative Care in HSCT

Pioneering randomized controlled trials (RCTs) in single institutions demonstrated that inpatient palliative care alongside transplant care significantly improved patient-reported QOL and mood during and after HSCT hospitalization (El-Jawahri et al., JAMA 2016; J Clin Oncol 2017). These studies reported smaller QOL declines at 2 weeks post-HSCT, lower depression and anxiety symptoms, and reduced symptom burden compared to usual care. Subsequent studies expanded these findings, showing persistent psychological benefits up to six months post-transplant.

The current multisite randomized trial by El-Jawahri et al. (J Clin Oncol 2025) represents a landmark advancement, enrolling 360 adults undergoing autologous or allogeneic HSCT at three academic centers. The study confirmed that inpatient PC, delivered twice weekly during HSCT hospitalization, led to better QOL, reduced depression, and fewer PTSD symptoms at the 2-week nadir compared to standard care. Notably, anxiety did not differ significantly.

Longitudinal analysis revealed a steeper decline in PTSD symptoms over six months in the PC arm, indicating sustained psychological benefit. These findings underscore palliative care’s role beyond symptom control, impacting long-term mental health.

Intervention Components and Mechanisms

PC interventions during HSCT focus on symptom management (pain, fatigue, nausea), psychological support, coping skills, illness education, and advance care planning. Weekly clinician surveys from trials indicate that PC visits frequently address coping and education, particularly among patients showing strong early QOL responses.

A secondary analysis showed that increased use of approach-oriented coping correlated with better QOL responses to PC, suggesting that fostering adaptive coping mechanisms is integral. Differences in supportive care medications, such as greater use of patient-controlled analgesia and atypical antipsychotics in the intervention group, were observed but did not mediate the improved outcomes, highlighting the importance of holistic palliative care strategies.

Caregiver-Focused Interventions

Caregivers of HSCT patients face considerable distress, with existential suffering exacerbated by witnessing patient challenges. A recent pilot study of nurse-led Meaning-Centered Psychotherapy for Cancer Caregivers (MCP-C) delivered via telehealth demonstrated high feasibility and acceptability. Participants valued the intervention’s transplant-specific knowledge and the connection to sources of meaning, which may alleviate caregiver existential distress and improve psychosocial outcomes. Larger RCTs are underway to assess efficacy.

Methodological Advances and Future Directions

The 2025 multisite trial employed rigorous methods with linear regression adjusting for baseline scores and longitudinal mixed-effects models for outcome trajectories. High enrollment rates (68.7%) and inclusion of both autologous and allogeneic HSCT patients enhance generalizability. The adoption of validated outcomes instruments such as FACT-BMT for QOL, Hospital Anxiety and Depression Scale, and PTSD Checklist strengthens the evidence.

Future research priorities include identifying patient subgroups most likely to benefit from PC, optimizing timing and delivery modalities, integrating symptom screening platforms like SPARK for tailored interventions, and evaluating cost-effectiveness.

Expert Commentary

The evidence firmly positions inpatient palliative care as a crucial adjunct during HSCT hospitalization, addressing the multidimensional symptom and psychological burdens inherent in transplant processes. The integration of PC services early and throughout hospitalization can mitigate declines in QOL and prevent prolonged psychological sequelae. While anxiety outcomes did not demonstrate significant group differences at week 2, longitudinal PTSD improvements suggest a trajectory of psychological benefit that merits further exploration.

The independence of benefits from specific medication use highlights that PC’s strength lies in comprehensive symptom management combined with psychosocial support and patient/caregiver education. Clinicians should recognize the value of routine PC involvement, moving beyond referral-based patterns toward integrated models.

Caregiver interventions, particularly meaning-centered approaches, are promising yet underexplored. Supporting caregivers’ psychological and existential needs may indirectly improve patient outcomes and reduce caregiver burnout.

Barriers to implementation include workforce limitations, reimbursement challenges, and variability in institutional culture around PC integration. Institutional leadership and transplant teams must prioritize embedded PC collaborations.

Conclusion

Recent multisite RCT evidence consolidates palliative care’s role in enhancing QOL and reducing depressive and PTSD symptoms in HSCT patients, with effects sustained up to six months post-transplant. Integrative approaches addressing symptom control, coping, and education are pivotal. Caregiver-focused interventions show feasibility and promise for broader adoption. Ongoing research must refine intervention components, identify high-yield populations, and develop scalable models to embed PC seamlessly into HSCT care pathways, ultimately improving holistic outcomes for patients and caregivers alike.

References

• El-Jawahri A, LeBlanc TW, Kavanaugh A, et al. Multisite Randomized Trial of Inpatient Palliative Care Intervention for Patients Undergoing Hematopoietic Stem Cell Transplantation. J Clin Oncol. 2025 Aug 20;43(24):2700-2711. doi:10.1200/JCO-25-00378. PMID: 40549982; PMCID: PMC12353685.
• El-Jawahri A, Traeger L, Kuzmuk K, et al. Effect of Inpatient Palliative Care on Quality of Life 2 Weeks After Hematopoietic Stem Cell Transplantation: A Randomized Clinical Trial. JAMA. 2016 Nov 22;316(20):2094-2103. doi:10.1001/jama.2016.16786. PMID: 27893130.
• El-Jawahri A, Traeger L, Park ER, et al. Effect of inpatient palliative care during hematopoietic stem-cell transplant on psychological distress 6 months after transplant: Results of a randomized clinical trial. J Clin Oncol. 2017 Nov 10;35(32):3714-3721. doi:10.1200/JCO.2017.73.2800. PMID: 28926288.
• LeBlanc TW, Tang WY, Traeger L, et al. Factors associated with early quality-of-life response to palliative care during hematopoietic cell transplantation. Blood Adv. 2025 May 13;9(9):2033-2043. doi:10.1182/bloodadvances.2024014574. PMID: 39908568.
• Fife BL, Rosenberg AR, Kavanaugh A, et al. Supporting Hematopoietic Stem Cell Transplant Family Caregivers: A Pilot Study of Nurse-Led Meaning-Centered Psychotherapy for Cancer Caregivers. Psychooncology. 2025 Apr;34(4):e70142. doi:10.1002/pon.70142. PMID: 40186356.
• White ML, Russell KM. Palliative care for patients undergoing stem cell transplant: intervention components and supportive care measures. Bone Marrow Transplant. 2021 Aug;56(8):1971-1977. doi:10.1038/s41409-021-01281-2. PMID: 33824441.