Abstract: Hematopoietic stem cell transplant (HSCT) for blood and bone marrow disorders is a costly procedure that requires complex treatment regimens. In addition to disease-related factors, comorbidity and psychosocial characteristics can affect transplant outcomes and cost of care. Post-HSCT health services utilization depends on multiple factors including psychosocial behavior and variations in health insurance coverage. We conducted a retrospective observational cohort study including 136 adult HSCT recipients. Patient suitability for transplant was scored using an abbreviated 6-item Psychosocial Assessment of Candidates for Transplantation scale. The association of psychosocial score with the hospital length of stay during the first year after HSCT was analyzed to determine whether a prospective psychosocial evaluation may have a prognostic significance for transplant outcomes. Availability of a care partner and health insurance were identified as additional factors that could predict post-HSCT health care costs.
Hematopoietic stem cell transplant (HSCT) has become an established therapy for patients with hematologic diseases. However, relapse or serious complications related to HSCT, including graft-vs-host disease (GVHD), sepsis, cytomegalovirus infection, and fungal infection still limit the success of the procedure and increase the financial costs of HSCT.1 As a result, HSCT for blood and bone marrow disorders has been recognized as a costly procedure that requires complex treatment regimens.
The number of stem cell transplants for hematologic malignancies has been growing continuously worldwide. The Center for International Blood and Marrow Transplant Research (CIBMTR) estimated that allogeneic transplants in the United States rose to 8539 in 2016 (up from 8474 in 2015) and autologous transplants surpassed 14,000 (up from 13,658 in 2015), demonstrating increase at a faster rate from transplants for plasma cell and lymphoproliferative disorders extending to older patients (>65 years).2 According to market research reports, the global hematopoietic stem cell transplantation market is expected to reach $7.796 billion by 2023.3,4
In the United States, one research report found that the average billed charges in 2017 for transplants was $8,287,826,800 for the allogeneic and $4,980,736,000 for autologous.5 Prior studies have identified possible cost contributors to be the health care system, conditioning regimen, GVHD prophylaxis, variations in supportive care, clinical outcomes, disease type, disease status at transplant, HLA matching, the graft source, the age and the health status of recipients, type and dosage of chemotherapy or radiation prior to transplant, complications during and after transplant, and genetic makeup.6,7
Hospital transplant admissions and 180 days posttransplant discharge are the major cost drivers for both allogeneic and autologous groups. Inpatient costs including room costs, pharmacy, and laboratory tests, account for the majority of the total costs. Immunosuppressants and other drugs account for 3% of the costs in both groups. In addition, nonmedical expenses, such as caregiver time, transportation, and local housing costs add to the high-cost estimates.6,7
A substantial variation in costs accumulated during the 100-day and 1-year post HSCT by graft type and conditioning regimen has been reported (from $181,933 to $408,876).8 In the first 100 days, median total health care costs have been estimated at $289,283 (for myeloablative allogeneic recipients), $253,467 (for nonmyeloablative and reduced intensity NMA/RIC allogeneic recipients), and $140,792 (for myeloablative autologous recipients).8 Cost of the HSCT admission makes up 73% to 76% of 100-day costs for myeloablative patients and 66% for those receiving NMA/RIC.8
HSCT recipients may experience extended and/or repeated hospital stays due to their immunocompromised nature. Significant risk factors for readmission include disease histology, Karnofsky performance score (KPS) of 80 or lower, increasing hematopoietic cell transplant comorbidity index (HSCT-CI), and length of stay (LOS) of 28 or more days posttransplant in both transplant groups. Other variables, including older age, lower CD34 counts in the graft, refractory disease, development of complications (atrial fibrillation, respiratory failure, or renal failure requiring dialysis) during hospital stay are moderately associated with higher probabilities of readmission in autologous transplants.9 Donor type, stem cell source, conditioning regimen, and documented infection during hospitalization have been linked with increased risk of readmission among allogeneic HSCT recipients.9
In addition to disease-related factors, comorbidity, psychosocial characteristics, variations in health insurance, adherence to therapy, and availability of a care partner can affect transplant outcomes and cost of care. Patients recovery from a HSCT can be influenced by multiple psychosocial factors. Pretransplant distress may vary depending on a number of aspects such as prior disease with relapse, treatment history, physical functioning, and psychological, financial, and social resources.10 Psychosocial factors such as presence of availability of a consistent care partner, mental health needs, psychological issues such as depression and severe anxiety, and compliance can impact risks of adverse outcomes including survival.10 Therefore, it is important to examine pretransplant psychosocial status when considering factors that contribute to a patient’s recovery.
There is an increasing need for better understanding of the importance of pretransplant psychosocial variables, as well as greater awareness of the predictive significance of these variables upon admission to the hospital or initiation of treatment. The National Marrow Donor Program (NMDP) recommends a comprehensive pretransplant evaluation to identify any psychosocial issues that would interfere with the transplant procedure/recovery.11 In accordance with these recommendations, transplant centers perform comprehensive evaluation, including psychosocial assessment for all patients considered for HSCT, to evaluate their candidacy for transplant. However, instruments to objectively characterize psychosocial status in this population are generally lacking. For example, the HSCT-CI captures only psychiatric disorders and does not measure psychosocial conditions of transplant candidates.9
Additionally, studies have established a relationship between the socioeconomic status (SES) and survival outcomes. Patients with Medicaid or uninsured are at increased risk of death from head and neck cancer when compared to patients with private insurance, after adjustment of a number of demographic factors including treatment, cancer stage, and SES. A significant effect of insurance status on mortality, quality of life as well as mental health in the autologous group has been observed.12-14 These studies suggest that insurance status may be one of the most prominent demographic factors that interacts with a patient’s overall health outcomes and that it should be considered along with examining other psychosocial variables.
The objective of this retrospective observational cohort study was to examine the impact of patients’ psychosocial and health insurance status, among other clinical factors, on post-stem cell transplant health services utilization. We sought to determine variables associated with hospital readmission and LOS within one year of discharge date following first HSCT in allogeneic and autologous transplant recipients. We also analyzed the association of psychosocial score with the hospital LOS during the first year after HSCT. The overall goal of the analysis was to identify associations and patterns that may improve HSCT outcomes and reduce hospitalizations posttransplant.
Methods
Participants
This retrospective single-center cohort study examined outcomes of patients from an academic medical oncology center who received an autologous or related/unrelated donor allogeneic HSCT using either a bone marrow or a peripheral blood stem cell (PBSC) source. Inclusion criteria for the cohort were adult patients with hematologic malignancies undergoing their first HSCT between 2013 and 2016. All patients had been treated according to the Foundation for Accreditation of Cellular Therapy (FACT) standards and clinical pathways used at the medical center.
Application of Abbreviated PACT Scale
Patient suitability for transplant was retrospectively scored using an abbreviated version of the Psychosocial Assessment of Candidates for Transplantation (PACT) scale.15 The original PACT scale includes 8 subscales grouped in the following 4 domains: social support, psychological health, lifestyle factors, and understanding of transplant and follow-up. Each scale contains a 5-point rating scale (1 is the lowest and 5 is the highest) and a 4-point initial and final rating independently based on the rater’s overall impressions, ranging from 0 (poor candidate) to 4 (excellent candidate). A lower score indicates higher psychosocial risk.
Due to the retrospective nature of this study, we were only able to analyze 3 of the 4 PACT domains in this study population: social support, psychological health, and lifestyle factors. All patients had been assessed by clinicians based on written psychosocial notes performed by clinical psychology staff according to the following 3 domains and 6 subscales (Box 1). The additional domain “understanding of transplant and follow-up” (ie, compliance and receptiveness to education) could not be analyzed, as specific questions addressing these aspects were not asked during psychosocial pretransplant evaluation.
Data Collection
We explored 3 sets of variables: clinical data (ie, the psychiatric or psychotherapeutic history were obtained from the patients’ records); sociodemographic data (ie, age, gender, marital status, and type of insurance obtained using institutional database); and transplant-specific data obtained from both the institutional database and CIBMTR Data Back to Center (DBtC).
Variables of interest included in HSCT-CI, age, sex, race, marital status, education, disease type, KPS at time of transplant (80 and lower vs 90/100), disease status and disease risk at time of transplant (stable disease/progressive disease vs partial response/complete response), mobilization regimen, comorbidity score, psychiatric comorbidity, and final PACT rating, as well as the duration of the hospital admission after transplant.
Outcome Measures and Statistical Analyses
The primary outcome was the hospital LOS during the first year after transplant expressed in number of days.
Data of patients undergoing autologous and allogeneic HSCT were examined separately. Patients were stratified into 2 groups: low risk (PACT scores of 3 and 4) and moderate/high risk (PACT scores of 1 and 2). We analyzed the association of the psychosocial score with the hospital LOS during the first year after HSCT. Patient and transplant characteristics were compared between patients with low and high final PACT score using the Chi-square test.
In addition to PACT rating, variables considered in univariable analyses included age, sex, race/ethnicity, diagnosis category, disease risk, HSCT-CI score, KPS, donor, and graft source.
We used Poisson’s regression to model the relationship between the mean LOS (number of days spent in hospital) during hospitalizations in the first year between 2 groups of patients: with lower (1,2) and higher (3,4) PACT scores while controlling for significant patient-, disease-, and treatment-related variables. We constructed 2 separate models for autologous and allogeneic HSCT, respectively. Poisson regression models included potentially useful independent variables (marital status, education, health insurance, KPS, etc).
We performed all analyses using SAS version 9.3. All
P values are 2-sided; P values of less than .05 were considered statistically significant.
Results
The study population included 96 autologous and 40 allogeneic adult recipients transplanted at the oncology center (N=136).
As shown in Table 1, the autologous transplant recipients with mean age 58 (range 24-78) were older than the allogeneic patients whose mean age was 39 (range 20-63). The ethnic composition of the sample was almost equally distributed between Caucasian (51%) and African Americans (46%) in the autologous group, and in the allogeneic group, 62.5% of transplant recipients were Caucasian, 30% were African American, and 7.5% Asian. Most were married or living with a partner (60% in the autologous group and 62.5% in the allogeneic group). More than half of the recipients in both groups had a commercial health insurance plan.
The most frequent indication for autologous transplant was multiple myeloma (73%). The most frequent indication for allogeneic was acute myeloid leukemia (43%). The disease risk at transplant was high in 22.5% of autologous transplants, and in 15% of allogeneic transplants.
The donor type in more than half of the allogeneic recipients was matched unrelated donor, and the source was PBSC in 35 (87.5%) and bone marrow in 5 (12.5%). All autologous transplants received PBSC.
KPS at time of transplant was 90 and lower in 65% of the allogeneic transplants and in 21% of the autologous transplants.
The median comorbidity score measured by HSCT-CI was 2 (range 0-7) in the allogeneic and 3 in the autologous group. In both groups, more than a half of the patients had some type of mental health comorbidity documented during the comorbidity assessment.
The median survival time after transplant was 737 days (range 4-1638) for autologous and 429 days (range 9-1613) for allogeneic. In the first year after transplant, 65% of the allogeneic patients were readmitted at least once, and 15% were never discharged. In the autologous group, 33% of transplant recipients were readmitted at least once.
Readmission and average LOS during subsequent hospitalizations was 19.3 (SD=28.58) for allogeneic and 1.8 days (SD=4.09) for autologous.
The rates of patients with high PACT scores (3,4) were almost equal in both groups: 26 (60%) in allogeneic and 60 (62.5%) in autologous. Factors associated with shorter hospital stay in autologous transplants were higher PACT scores (relative risk [RR], 0.45; 95% CI, 0.77-0.11; P=.0077), availability of a care partner (RR, 0.58; 95% 0.97-0.20; P=.0028), and underinsured/Medicaid status (RR, 0.81; 95% CI, 0.01-1.63; P=.05). In the allogeneic group, higher PACT scores (RR, 0.74, 95% CI, 0.92-0.56; P<.0001) were associated with shorter hospital stays (Table 2).
Among patients undergoing allogeneic transplants, higher final PACT scores indicated less posttransplant utilization of health services (P<.0001). Underinsured/Medicaid and commercial health insurance patients spent longer periods in hospital compared with Medicare and mixed health insurance. Education beyond high school suggested shorter LOS in hospital LOS.
In autologous transplants, higher psychosocial score assessed by PACT scale was associated with shorter hospital stay during the first-year posttransplant (P=.011). Underinsured/Medicaid transplant recipients were hospitalized for shorter periods posttransplant (P=.05) as compared with recipients with commercial health insurance (P<.0001). Medicare and mixed health insurance did not affect significantly the hospital LOS. Availability of a stable care partner predicts fewer days in hospital (P=.012).
Marital/living with a partner status was associated with longer hospital stays (P=.0016). When controlling for disease risk, patient performance status (KPS) was a strong predictor of health services utilization.
Discussion
Our study findings highlight a link between psychosocial functioning and health services utilization in both allogeneic and autologous transplant recipients. In addition to the HSCT-CI score, a prospective comprehensive psychosocial evaluation, such as PACT, may help predict health services utilization and cost of care. Assessment of psychosocial factors, availability of a care partner, and health insurance may help estimate post-HSCT health care cost related to hospital admissions and LOS.
Clinical pathways and treatment guidelines should reflect the need for a thorough psychosocial pretransplant assessment. It should be noted, though, that patients experience a high degree of psychological distress from the time of evaluation through the posttransplant period. The psychosocial status of patients has important implications for transplant outcomes, and it can change throughout the care continuum.
The PACT scale (or similar validated scales) can be used in pretransplant psychosocial assessment to identify patients at higher risk for readmission. The PACT scale was originally validated in a study on clinical decisions regarding the acceptability of 47 patients for heart and liver transplantation.15 Interrater reliability was high (intraclass correlation=0.85) with overall 96% agreement between raters on the decision to proceed with a transplant. Partial correlations between individual items and final ratings ranged from 0.39 (drug and alcohol use) to 0.72 (personality and psychopathology). The PACT scale appears to be a useful instrument for the pretransplant psychosocial evaluation in examining the weight of various factors in patient selection process clinical outcomes prediction. Significant relationships between PACT subscales and clinical outcomes in candidates for allogeneic stem cell transplant transplantation have been reported.16 The psychosocial assessment of the patients demonstrated that better compliance with medications and medical advice correlated with lower in-hospital mortality, shorter LOS, and readmission duration, as well as faster neutrophil and platelet engraftment.16
Lower PACT scores in both groups of this study were associated with increased LOS. These findings have potentially significant financial implications in terms of operational costs as well as costs of care for a patient regarding supplies, staffing, and facility expenses. Longer LOS can negatively influence outcomes by increasing the risk of hospital-acquired conditions.
It is possible that the observed relationship between pretransplant psychological functioning and posttransplant outcomes are affected by adherence to treatment. Patients experiencing psychologic distress may be less likely to adhere to the complex transplant regimen, which could negatively affect medical outcomes. A thorough psychosocial evaluation before and after HSCT is recommended to discover potential adherence challenges and could be included in existing clinical pathway programs. Previous research has shown that depression is predictive of nonadherence to treatment regimens across a variety of medical diagnoses.17
In accordance with previously published literature,12 our findings also suggest an additional risk to recovery might be patient’s health insurance status. Underinsured individuals may experience worse psychosocial functioning prior to transplant.
Some limitations of our study have to be considered. First, we did not use prospective PACT scoring, therefore, the retrospective PACT scoring could have been prone to raters’ bias. Second, findings are limited to a single academic hospital and need to be ascertained in larger multicenter studies. Third, we were unable to comment on the higher psychosocial risk as a factor for nonadherence to therapeutic regimens, which is generally not evaluated consistently pretransplant. Additionally, the impact of insurance status across all of the psychosocial and health outcomes is an important area for further exploration as it could serve as an impediment to overall recovery. Furthermore, the influence of certain clinical factors that could have contributed to the resource utilization and cost in HCT recipients was not included in statistical models (for example, exact medication dosages, the type of comorbidity, and GVHD grade).
Conclusion
Our study highlights the association between quantified pretransplant evaluation and posttransplant outcomes. Prospective comprehensive psychosocial evaluation may help predict health services utilization and care costs. Consideration of patients’ psychosocial factors, availability of a care partner, and health insurance status may help estimate post-HSCT health care cost related to hospital admissions and LOS. Future research should focus on the dynamics of interaction between psychosocial functioning, treatment adherence, and clinical outcomes.
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