In 2006, a group of investigators at the Cleveland Clinic conducted a survey study of hematopoietic cell transplantation (HCT) professionals across the United States in order to better understand what makes a potential HCT candidate ineligible from a psychosocial standpoint [1]. In other words, regarding psychosocial vulnerabilities, where do HCT providers draw the line and decline an otherwise eligible patient a transplant? The vast majority of the 597 survey responders indicated that active suicidal ideation, active use of addictive illicit drugs, a history of medical noncompliance (missing appointments, self-discontinuing medications), and lack of an identified caregiver were psychosocial issues so concerning as to warrant not proceeding with HCT. At the same time, the qualitative data generated from the study revealed that in reality most providers take a more nuanced approach to psychosocial limitations, as evidenced by a responding physician’s statement that, “These are not black and white issues… In general we try to make transplant available if there is a reasonable chance that a patient will have adequate support.”

In the ensuing years, empirical evidence linking psychosocial limitations to HCT outcomes has been inconsistent. Some studies demonstrate pre-transplant psychosocial assessments to be predictive of overall survival (OS) following HCT [2,3,4]; whereas, others have found no relationship with OS, but a significant association between psychosocial vulnerabilities and non-relapse mortality (NRM) [5]. However, single-institution reports consistently demonstrate a relationship between pre-HCT psychosocial assessments and length of HCT hospitalization, as well as days alive and outside of the hospital within 100 days of HCT [2, 5, 6]. Although not survival outcomes, these endpoints have increasing utility from a health economics, health policy, and patient quality-of-life standpoint.

For these reasons, the report by the Richardson and colleagues in this issue of Bone Marrow Transplantation is both timely and important. Using the transplant evaluation rating scale (TERS) [7, 8], a validated psychosocial screening tool commonly applied to HCT, the authors analyzed the relationship between pre-HCT psychosocial risk and cumulative incidence rate (CIR) of hospital readmission in the first 90 days following HCT. Among 395 consecutive HCT recipients (218 autologous; 177 allogeneic) who underwent pre-HCT psychosocial assessments at the Ohio State University, both mild (HR = 1.56 (95% CI: 1.05–2.33), p = 0.03) and moderate (HR = 2.30 (95% CI: 1.33–3.97), p = 0.003) psychosocial risk by TERS were independently associated with hospital readmission relative to no risk. Strikingly high rates of hospital readmissions were seen in patients with moderate psychosocial risk undergoing either autologous HCT (32% CIR of readmission) or allogeneic HCT (65% CIR of readmission). Specific TERS subcategories associated with readmission included the presence of an Axis I or II psychiatric disorder (HR = 1.81 (95% CI: 1.25 2.64), p = 0.002) and evidence of poor coping skills (HR = 1.64 (95% CI: 1.03–2.61), p = 0.04). Fifty-six percent of the patients identified by the TERS as medically non-compliant were readmitted within 90 days of HCT (i.e., five of nine non-compliant patients readmitted). As expected, the authors found no significant associations between psychosocial risk and OS or NRM.

These data add to the growing literature that standardized the psychosocial risk assessments of potential HCT candidates uncover relevant information that may aid HCT prognostication and patient selection. However, similar to other reports on this topic, the study by the Richardson and colleagues is limited to retrospective data from a single institution. Comparison of the findings of this study to others in the field is hampered by the ethnically and racially homogenous population included (90% non-Hispanic white) and the difficulty extrapolating across HCT studies that utilize a variety of different psychosocial screening tools (most commonly used are the TERS [7], the Psychosocial Assessment of Candidates for Transplantation [6], and the Stanford Integrated Psychosocial Assessment for Transplantation [9].

As HCT and other intensive and expensive cellular therapeutic modalities are considered for increasingly older, sicker, and more complicated patients, well validated and reproducible risk scoring systems are necessary in order to guide providers and patients. Similarly, as value-based care and cost containment strategies escalate in importance, a greater evidence base regarding the psychosocial factors that determine heightened risk for HCT morbidity, mortality, and health-care utilization is warranted. As a start, standardization of the psychosocial assessment instruments across HCT centers should be promoted in order to conduct well-designed multicentered confirmatory studies linking the psychosocial assessments to HCT outcomes.

Should validation confirm that the psychosocial limitations adversely impact HCT outcomes, the subsequent pressing issue is how to translate that knowledge into testable interventions. The lack of well-defined mechanisms underlying the HCT complications associated with psychosocial risk hinder the classical notion of targeted interventions (e.g., medication for depression). The findings by Richardson and colleagues illustrate this challenge—for example, infections accounted for the increase in hospitalizations among those at higher psychosocial risk [8]. We believe that system-based interventions will be needed as suggested by the authors “multidisciplinary” approach at their institution in response to these findings. This might include a combination of psycho-oncology services for patients and caregivers, financial support, and palliative care or perhaps multidisciplinary teams for patients deemed at high risk based on the psychosocial factors [10].