Specific Comorbidities Are Associated with Poor Outcomes in Adolescents and Young Adults Undergoing Allogeneic Stem Cell Transplantation

Introduction:Given the significant morbidity and mortality of allogeneic hematopoietic stem cell transplantation (HCT), a hematopoietic stem cell transplantation - comorbidity index (HCT-CI) was previously developed in adults to help risk-stratify patients prior to transplant. Adolescent and young adult (AYA) patients typically have less comorbidities than older adults, yet they still have significant rates of non-relapse mortality (NRM) following allogeneic HCT. We sought to demonstrate that poor outcomes among AYA patients that had undergone allogeneic HCT were likely associated with specific comorbidities that are seen more commonly in this population.

Methods: This was a retrospective study of 241 patients aged 15-39 years who underwent allogeneic HCT from January 2005 - December 2015 at UCLA. Patients were excluded if they had a prior allogeneic HCT. Data was collected on the fifteen comorbidities from the original HCT-CI study, as well as other possible risk factors in the AYA population including a practical and psychosocial variable and history of congenital heart disease. The primary endpoints for the analysis were the cumulative incidence of NRM and overall survival (OS) after allogeneic HCT.

Results: Demographic data for patients with allogeneic HCT was demonstrated to be diverse, as 63% of patients were described as non-White. OS for this population at 1, 3, and 5 years was 62%, 52%, and 46%, respectively, with a median overall survival of 4 years. NRM at 1, 3, and 5 years was 26%, 31%, and 32%, respectively. Most deaths (62%) were not attributed to relapse. Of the comorbidities that are included in the HCT-CI, pulmonary, hepatic, infectious, cardiac, obesity, and psychiatric were the only pre-transplant risk factors to have greater than 10% prevalence in the patients studied. The pulmonary comorbidity had the highest prevalence rate (55%). A practical and psychosocial component was the second most common comorbidity in this population (35%). Financial concerns were the most frequent reason (23%) for patients to be considered positive for this risk factor. History of a psychiatric disorder was significantly associated with a greater rate of NRM (HR = 1.74; 95% CI: 1.02-2.97, p=0.041) as was presence of severe lung disease (HR = 2.49; 95% CI 1.35-4.59, p=0.003).

Discussion: We have shown that AYAs that received allogeneic HCT had poor outcomes and most deaths were attributed to treatment-related causes. In addition, among several previously described comorbidities and a novel practical and psychosocial component, a history of psychiatric disease and severe lung disease were associated with higher rates of NRM in this younger patient population prior to allogeneic HCT. This further supports the notion that AYA patients have unique needs and we believe that a simpler and more efficient HCT-CI should be developed to better assess these patients prior to transplant. Further, our preliminary results suggest that interventions aimed at targeting modifiable risk factors may improve outcomes for AYA patients undergoing allogeneic HCT. Future research is needed to validate our findings in a larger prospective study.