Multimodal Psychosocial Intervention for Family Caregivers of Patients Undergoing Hematopoietic Stem Cell Transplantation (HCT): A Randomized Clinical Trial

Abstract

Background:

Caregivers of patients undergoing HCT experience immense caregiving burden prior to, during, and after HCT.

Methods:

We conducted an unblinded, randomized trial of a psychosocial intervention (BMT-CARE) for caregivers of patients undergoing autologous and allogeneic HCT at Massachusetts General Hospital. Caregivers were randomly assigned to BMT-CARE or usual care. BMT-CARE was tailored to the HCT trajectory and integrated treatment-related education and self-care with cognitive-behavioral skills to promote coping. Caregivers assigned to BMT-CARE met with a trained interventionist (psychologist or social worker) in-person, via telephone or videoconferencing for six sessions starting prior to HCT and up to day+60 post-HCT. The primary endpoint was feasibility defined as having at least 60% of eligible caregivers enroll and complete ≥ 50% of the intervention sessions. We assessed Caregiver quality of life (QOL; CareGiver-Oncology-Questionnaire), caregiving burden (Caregiver-Reaction-Assessment), psychological distress (Hospital-Anxiety-and-Depression-Scale), self-efficacy (Cancer-Self-Efficacy-Scale-Transplant), and coping (Measures-of-Current-Status) at baseline, 30 days, and 60 days post-HCT. We used mixed linear effect models to assess the effect of BMT-CARE on outcomes longitudinally.

Results:

We enrolled 72.5% (100/138) of eligible caregivers and 80% attended ≥50% of intervention sessions. Caregivers randomized to BMT-CARE reported improved QOL (B=6.11, 95%CI[3.50,8.71], p<.001) reduced caregiving burden (B=−6.00, 95%CI[−8.49,−3.55] p<.001), lower anxiety (B=−2.18, 95%CI[−3.07,−1.28], p<.001) and depression (B=−1.23, 95%CI[−1.92,−0.54], p<.001) symptoms, and improved self-efficacy (B=7.22, 95%CI[2.40,12.03], p=.003) and coping skills (B=4.83, 95%CI[3.04,6.94], p<.001) compared to the usual care group.

Conclusions:

A brief multimodal psychosocial intervention tailored for caregivers of HCT recipients is feasible and may improve QOL, mood, coping, and self-efficacy while reducing caregiving burden during the acute HCT period.

Condensed Abstract:

In this randomized clinical trial of 100 caregivers of patients undergoing HCT, a brief psychosocial intervention (BMT-CARE) was feasible with high enrollment and retention rates, and led to improvement in caregiver QOL, psychological distress, coping, and self-efficacy while reducing caregiving burden during the acute HCT period. Thus, BMT-CARE is a promising intervention and should be tested in future multi-site trials.

INTRODUCTION

Family members and close friends (caregivers) play a critical role in caring for their loved ones during cancer treatment.^1-5 Hematopoietic stem cell transplantation (HCT) is a commonly utilized, potentially curative therapy for patients with hematologic malignancies that requires a prolonged hospitalization and substantial recovery period.^{6, 7} Prior to HCT, caregivers experience immense psychological distress as they prepare for their loved ones’ hospitalization for HCT and cope with the uncertainty of the patients’ prognosis.^8-12 During HCT, caregivers’ distress remains elevated as their loved ones receive high-dose chemotherapy associated with multiple toxicities, physical symptoms, and a prolonged hospitalization.^{9-11, 13} Finally, in the months post-HCT, the caregiver manages ongoing physical symptoms, attends multiple outpatient appointments, and navigates complex medication schedules while coping with the uncertainty of the illness.^12-14 Consequently, caregivers of HCT recipients have prolonged caregiving burden that negatively impacts their quality of life (QOL) and mood. ^12-15

Despite their substantial caregiving burden, relatively few interventions target the needs of caregivers of HCT recipients, and there are no interventions that span the transplant course by addressing caregiving burden before, during, and immediately after HCT.^{1, 12-14} Two studies examined the effect of problem-solving and stress management interventions for caregivers of allogeneic HCT recipients only after the patients’ hospitalization for HCT,^16-18 but did not target caregivers’ needs before and during HCT when caregivers report the highest distress.^{11, 19} Moreover, given the extent of caregiving burden in this population, more comprehensive multimodal psychosocial interventions spanning the HCT course are needed to promote caregiver coping skills and improve overall QOL while reducing burden and distress.^{11, 13, 15, 20}

We conducted a single-center randomized clinical trial to evaluate the feasibility and preliminary efficacy of a multimodal psychosocial intervention for caregivers of patients undergoing HCT (BMT-CARE) for improving caregiver QOL, caregiving burden, mood, and self-efficacy. We hypothesized that BMT-CARE would be feasible with at least 60% of eligible caregivers enrolling in the study and completing at minimum of 50% of the planned intervention sessions. We also hypothesized that caregivers assigned to BMT-CARE would report better QOL, lower caregiving burden, and lower symptoms of anxiety and depression, as well as higher perceived self-efficacy, compared to caregivers assigned to usual care at day 60 post-HCT.

METHODS

Study Design

We conducted a non-blinded, randomized clinical trial of a multimodal psychosocial intervention (BMT-CARE) versus usual care for caregivers of patients undergoing autologous and allogeneic HCT (Clinicaltrials.gov identifier: NCT03328663). The study was conducted at the Massachusetts General Hospital Cancer Center (MGH; Boston, Massachusetts). The Dana Farber/Harvard Cancer Center Institutional Review Board approved the study protocol, and all caregivers provided informed consent.

Study Participants

Caregiver eligibility criteria included being: 1) at least 18 years old; 2) a relative or a friend of a patient undergoing autologous or allogeneic HCT who either lives with the patient or has in-person contact with them at least twice per week and is identified by the patient as the primary caregiver for HCT; and 3) able to read and respond to questions in English or complete questionnaires with minimal assistance from an interpreter.

A research assistant (RA) reviewed the transplant clinic schedule to identify all patients scheduled for their HCT consent appointment. The RA contacted the oncologist to gain permission to approach the caregiver for study participation and inquire about any concerns regarding their participation. The RA then approached consecutively eligible caregivers to introduce the study and conduct informed consent during the clinic visit when their loved ones consented for HCT. If a patient did not have a caregiver present at the HCT consent visit, the RA requested patient permission to contact their identified caregiver by telephone about study participation. Caregivers had the option of enrolling in the study over the telephone with a verbal consent. Caregivers then completed baseline self-report assessment immediately after finishing informed consent procedures or within a 72-hour window from study enrollment.

Randomization:

After the RA obtained informed consent and collected baseline self-report assessments, caregivers were randomly assigned to receive either BMT-CARE or usual care. Participants were randomized in a 1:1 fashion, stratified by type of transplant (autologous or allogeneic), by the Office of Data Quality using a computer-generated number sequence, which was concealed until after group assignment. The Dana Farber/Harvard Cancer Center Office of Data Quality was responsible for participants’ registration and assignment to the study groups, but was not involved in other study procedures. Caregivers, oncology clinicians, and study investigators were not blinded to the group assignment.

The BMT-CARE Intervention

Caregivers assigned to the intervention received the BMT-CARE intervention in addition to usual care. Study team consisting of oncologists and psychologists collaboratively developed the structured, manualized BMT-CARE intervention using findings from our prior longitudinal study describing caregiver burden and distress during HCT, skills adapted from a previous skills-based psychosocial intervention in cancer, and a thorough review of the literature.^{11-13, 21} We then refined the intervention content and structure based on qualitative feedback from an open pilot study with six caregivers of patients undergoing HCT. The finalized BMT-CARE intervention is a 6-session caregiver-directed coping skills intervention that integrates HCT-related education with cognitive-behavioral strategies to enhance caregiver knowledge and skills across the transplant trajectory. Skills are uniquely tailored to expected challenges along the transplant continuum and comprise the following essential components: 1) education to address preparedness, manage expectations, and develop caregiving skills such as symptom and medication management, mobilization of social supports, and assessment of post-discharge needs during the HCT course; 2) cognitive-behavioral skills-based strategies to facilitate effective coping, cognitive reframing, mindfulness, communication, and acceptance while living with uncertainty; and 3) behavioral strategies for self-care to promote caregiver physical and mental health. BMT-CARE included four weekly and two semi-monthly individual sessions, lasting approximately one hour each, starting prior to HCT and continuing up to day +60 post-HCT. In-person intervention sessions were held in a private office. Each caregiver was given a BMT-CARE workbook that included in-session and at-home practice exercises to facilitate learning and skill acquisition. BMT-CARE interventionists were trained study therapists (i.e., licensed clinical psychologist, licensed social worker, or clinical psychology fellow) who met with caregivers in-person, or via telephone or videoconferencing.

Prior to meeting with any participants, all study interventionists completed a half-day in-person BMT-CARE training and attended weekly telephone-based group clinical supervision throughout the course of the study with the lead licensed clinical psychologist (JJ). To ensure the fidelity of the intervention, we audio-recorded intervention sessions and reviewed 10% of sessions at random. Two investigators (AE and JJ) independently reviewed the audio-recorded visits and rated adherence to the intervention content using a pre-specified list of intervention topics by session. Treatment fidelity scores range from 0-100%, and we considered scores ≥80% to be adherent to the intervention protocol based on prior studies.^{22, 23}

Usual Care

Caregivers randomized to usual care did not receive BMT-CARE. Per usual care across most transplant centers, patients and caregivers met with the transplant social worker once prior to HCT to address any issues or concerns. The social workers are also available as needed to provide additional support post-HCT. The social workers delivering usual care were different than those delivering BMT-CARE

Caregiver-Reported Outcome Measures

Caregivers completed a baseline assessment which included a demographic questionnaire and self-report measures within a 72-hour window after providing informed consent and prior to randomization. Caregivers also completed the self-report measures at day +30 (+ 7-day window), and day +60 (+20-day window) post-HCT. The RA , unblinded to randomization, provided caregivers with the self-reported study questionnaires in person, by secure email, or regular mail.

We administered the Caregiver Oncology QOL questionnaire (CarGOQOL) to measure caregiver QOL.²⁴ The CarGOQOL is a 29-item instrument that measures ten QOL domains and can be analyzed using a composite QOL score (normalized score range 0-100) with higher scores indicating better QOL. We also used the Caregiver Reaction Assessment (CRA) to assess caregiving burden. The CRA consists of 24 items that address five caregiving burden domains.²⁵ A CRA total score (range 24-120) can be obtained, with higher scores indicating higher caregiving burden.²⁶

To assess mood and anxiety symptoms, caregivers completed the Hospital Anxiety and Depression Scale (HADS).²⁷ The 14-item HADS consists of two subscales assessing anxiety and depression symptoms in the past week. Subscale scores on the HADS range from 0 (no distress) to 21 (maximum distress).

We used the Cancer Self-Efficacy Scale-Transplant (CASE-T) to measure caregivers’ confidence in managing the impact of HCT.^{16, 28} The CASE-T consists of 17 items (range 0-170) with higher scores indicating greater self-efficacy. We also used the Measure of Current Status (MOCS) to assess caregivers’ perceived coping skills such as the ability to relax, restructure maladaptive thoughts, and choose an appropriate coping strategy. The MOCS consists of 13 items (total score range 0-52) with higher scores indicating greater coping skills.²⁹

Statistical Analysis

We performed statistical analyses using STATA (v9.3). All participants’ characteristics and outcomes were summarized as frequencies and percentage for categorical variables and mean ± SD for continuous variables. We evaluated inter-coder reliability in measuring intervention fidelity using kappa statistics. A two-sided P-value < 0.05 was considered statistically significant.

The primary endpoint of the study was feasibility of enrollment and intervention delivery. BMT-CARE was deemed feasible if at least 60% of eligible caregivers enrolled in the study and 60% of those assigned to the intervention completed a minimum of 50% of planned intervention sessions. We chose a sample size of 100 caregivers based on the feasibility of completing the project during the study timeframe. The proposed sample size was also sufficient to provide us with preliminary data that could be utilized to determine effect sizes for our caregiver-reported outcomes and inform power considerations for a future multi-site study. Prior studies suggest that a minimum of 30 participants per group are needed to estimate a parameter when examining preliminary intervention effects.^{30, 31}

To test caregiver-reported outcomes, we first used analysis of covariance (ANCOVA) models controlling for baseline criterion scores to examine the effect of BMT-CARE on caregiver QOL (CarGOQOL), caregiving burden (CRA), depression and anxiety symptoms (HADS), self-efficacy (CASE-T), and coping skills (MOCS) at day 60 post-HCT based on available cases without accounting for missing data. We then used mixed linear effect models using Maximum Likelihood to account for missing data to examine change in outcomes of interest across all three time points.

RESULTS

Baseline Characteristics

We approached 138 caregivers for study participation between 12/2017 and 4/2019, and 72.5% (100/138) enrolled [Figure 1]. Eight caregivers became ineligible after enrollment due to patient’s death prior to HCT or aborted plans for HCT. Enrolled caregivers were mostly white (92.3%, 85/92), and the majority were female (69.6%, 68/92), married to the patient (81.5%, 75/92), with a median age of 61 (range 22-93) [Table 1]. Most (64.1%) caregivers were caring for an allogeneic HCT recipient. There were no meaningful differences in caregiver characteristics between study groups at baseline. Overall, 83 and 87 caregivers completed the day 30 and day 60 post-HCT assessments with a missing data rate of 9.8 % and 5.4%, respectively.

Figure 1: Consort diagram:

HCT = Hematopoietic stem cell transplantation

Table 1: Caregivers’ baseline characteristics:

MPN = Myeloproliferative neoplasm; MDS = Myelodysplastic syndrome; SD = Standard Deviation; QOL = Quality of Life; CarGOQOL= Caregiver Oncology Quality of Life Questionnaire; CRA = Caregiver Reaction Assessment; HADS-A= Hospital Anxiety and Depression Scale- Anxiety Symptoms; HADS-D = Hospital Anxiety and Depression Scale – Depression Symptoms, CASE-T = Cancer Self-Efficacy Scale-Transplant; MOCS = Measure of Current Status.

Caregiver Characteristics	BMT-CARE (N = 45)	Usual Care (N = 47)
Age, Median (range)	58 (23-75)	62 (22-93)
Female Sex, n (%)	31 (68.9%)	33 (70.2%)
Relationship to Patient, n (%)
Married	36 (80.0%)	39 (83.0%)
Child	5 (11.1%)	1 (2.1%)
Parent	3 (6.7%)	3 (6.4%)
Sibling	1 (2.2)	3 (6.4%)
Divorced	0 (0.0)	1 (2.1%)
Race, n (%)
White	42 (93.3%)	43 (91.5%)
American Indian	0 (0.0)	2 (4.3%)
Black	2 (4.5%)	1 (2.1%)
Other	1 (2.2%)	1 (2.1%)
Hispanic Ethnicity, n (%)	1 (2.2%)	1 (2.1%)
Religion, n (%)
Catholic	18 (40.0%)	22 (46.8%)
Non-Catholic Christian	13 (28.9%)	14 (29.8%)
None	8 (17.8%)	6 (12.8%)
Jewish	4 (8.9%)	3 (6.4%)
Atheist	0 (0.0)	2 (4.2%)
Other	2 (4.4%)	0 (0.0%)
Education, n (%)
High school	10 (22.2%)	11 (23.4%)
College	24 (53.3%)	27 (57.4%)
Post-Graduate Degree	11 (24.5%)	9 (19.2%)
Employment, n (%)
Employed	22 (48.9%)	27 (57.4%)
Retired	14 (31.1%)	14 (29.8%)
Caring for Home or Family	4 (8.9%)	4 (8.5%)
Unemployed	2 (4.4%)	2 (4.3%)
Disabled	3 (6.7%)	0 (0.0%)
Patient Diagnosis, n (%)
Acute Leukemia	17 (37.8%)	15 (31.9%)
Lymphoma	10 (22.2%)	11 (23.4%)
Multiple Myeloma	10 (22.2%)	7 (14.9%)
MPN/MDS	8 (17.8%)	14 (29.8%)
Transplant Type, n (%)
Allogeneic	28 (62.2%)	31 (65.9%)
Autologous	17 (37.8%)	16 (34.1%)
QOL (CarGOQOL), mean (SD)	73.24 (10.34)	77.66 (12.61)
Caregiving burden (CRA), mean (SD)	55.27 (11.93)	47.28 (11.43)
Anxiety Symptoms (HADS-A), mean (SD)	7.80 (3.92)	6.40 (4.09)
Depression Symptoms (HADS-D), mean (SD)	4.92 (2.80)	3.51 (3.43)
Self-Efficacy (CASE-T)	138.52 (24.60)	146.78 (23.33)
Coping Skills (MOCS)	30.48 (8.73)	33.80 (8.63)

Feasibility of BMT-CARE

Overall, 72.5% (100/138) of eligible caregivers enrolled in the study and 80% (36/45) attended at least 50% of the intervention sessions, with 66.7% (31/45) completing all six intervention sessions [Figure 1]. The median number of intervention sessions was 6 (range 0-6), and the median duration of the sessions was 55 minutes (range 25-80). Approximately 46% of the intervention sessions occurred over the telephone, and 4% were delivered over videoconference. Treatment fidelity was 80% or higher for all sessions (range 80% - 100%) (intercoder kappa statistic = 0.76).

Caregiver Reported Outcomes

Table 2 shows the effect of BMT-CARE on caregivers’ outcomes at day 60 post-HCT. Caregivers assigned to BMT-CARE reported better QOL (adjusted means: 81.22 [95%CI 77.69, 84.74] vs. 70.96 [95%CI 67.56, 74.36], Cohen’s d = 0.68, P < 0.001), and lower caregiving burden (adjusted means: 46.95 [95%CI 43.62, 50.29] vs. 55.06 [95%CI 51.81, 58.31], Cohen’s d = 0.73, P = 0.001) compared to caregivers receiving usual care at day 60 post-HCT. In addition, caregivers assigned to the CARE intervention reported fewer symptoms of anxiety (adjusted means: 3.62 [95%CI 2.47, 4.77] vs. 7.22 [95%CI 6.11, 8.33], Cohen’s d = 0.96, P < 0.001) and depression (adjusted means: 2.85 [95%CI 2.02, 3.68] vs. 4.40 [95%CI 3.60, 5.20], Cohen’s d = 0.57, P < 0.001) compared to those receiving usual care. BMT-CARE intervention participants also reported higher self-efficacy and coping skills at 60 days post-HCT compared to those receiving usual care [Table 2].

Table 2: Effect of CARE intervention on caregiver-reported outcomes at 60 days post-HCT:

Results of ANCOVA models controlling for baseline values for the criterion outcome. CI = Confidence Interval; QOL = Quality of Life; CarGOQOL= Caregiver Oncology Quality of Life Questionnaire; CRA = Caregiver Reaction Assessment; HADS-A= Hospital Anxiety and Depression Scale- Anxiety Symptoms; HADS-D = Hospital Anxiety and Depression Scale – Depression Symptoms, CASE-T = Cancer Self-Efficacy Scale-Transplant; MOCS = Measure of Current Status.

Caregiver Outcomes 60 Days Post-HCT	Sample Size	Group Assignment	Adjusted Mean Score	95% CI	Cohen’s D	P-Value
QOL (CarGOQOL)	87	Usual Care Intervention	70.96 81.22	67.56 , 74.36 77.69 , 84.74	0.68	<0.001
Caregiving Burden (CRA)	86	Usual Care Intervention	55.06 46.95	51.81 , 58.31 43.62 , 50.29	0.73	0.001
Anxiety Symptoms (HADS-A)	87	Usual Care Intervention	7.22 3.62	6.11 , 8.33 2.47 , 4.77	0.96	<0.001
Depression Symptoms (HADS-D)	87	Usual Care Intervention	4.40 2.85	3.60 , 5.20 2.02 , 3.68	0.57	0.009
Self-Efficacy (CASE-T)	82	Usual Care Intervention	147.06 156.20	141.56 , 152.57 150.69 , 161.71	0.51	0.023
Coping Skills (MOCS)	83	Usual Care Intervention	28.02 36.54	25.41 , 30.64 33.88 , 39.19	0.98	<0.001

Using mixed linear effects models to examine the data longitudinally across all timepoints with Maximum Likelihood to impute missing data [Table 3], caregivers assigned to BMT-CARE reported better QOL (B = 6.11, [95%CI 3.50, 8.71], P < 0.001), lower caregiving burden (B = −6.02, [95%CI −8.49, −3.55], P < 0.001), and fewer symptoms of anxiety (B = −2.18, [95%CI −3.07, −1.28], P < 0.001) and depression (B = −1.23, [95%CI −1.92, −0.54], P < 0.001) compared to those receiving usual care. Caregivers assigned to BMT-CARE also reported improvement in self-efficacy (B = 7.22, [95%CI 2.40, 12.03], P = 0.003), and coping skills (B = 4.83, 95%CI [3.04, 6.94], P < 0.001) compared to those receiving usual care.

Table 3: Longitudinal effects of CARE intervention on caregiver-reported outcomes:

Results of mixed linear effect models using Maximum Likelihood to impute missing data. CI = Confidence Interval; QOL = Quality of Life; CarGOQOL= Caregiver Oncology Quality of Life Questionnaire; CRA = Caregiver Reaction Assessment; HADS-A= Hospital Anxiety and Depression Scale- Anxiety Symptoms; HADS-D = Hospital Anxiety and Depression Scale – Depression Symptoms, CASE-T = Cancer Self-Efficacy Scale-Transplant; MOCS = Measure of Current Status.

Caregiver Outcomes (N = 92)	Group * Time Estimate	95% CI	P- Value
QOL (CarGOQOL)	6.11	3.50 , 8.71	<0.001
Caregiving Burden (CRA)	−6.02	−8.49 , −3.55	<0.001
Anxiety Symptoms (HADS-A)	−2.18	−3.07 , −1.28	<0.001
Depression Symptoms (HADS-D)	−1.23	−1.92 , −0.54	<0.001
Self-Efficacy (CASE-t)	7.22	2.40 , 12.03	0.003
Coping skills (MOCS)	4.83	3.04 , 6.94	<0.001

DISCUSSION

The findings of this trial demonstrate that a multimodal psychosocial intervention spanning the HCT trajectory is feasible with promising efficacy for improving caregiver-reported outcomes. Almost three quarters of eligible caregivers enrolled in the study, and over two thirds completed all intervention sessions. BMT-CARE led to a significant improvement in caregiver QOL, caregiving burden, anxiety and depression symptoms, as well as self-efficacy and coping skills. These encouraging findings warrant further testing in a multi-site randomized clinical trial.

Despite recruiting caregivers at the time of heightened stress prior to HCT,^{11, 19, 32-34} BMT-CARE was feasible with high enrollment and retention rates. These findings are particularly relevant given the challenges of recruiting caregivers for supportive care interventions, especially with the competing demands on caregivers’ time.^{5, 13, 35-37} Importantly, approximately half of the BMT-CARE intervention sessions took place over the telephone or via video conferencing, which allows for a more scalable and potentially disseminable intervention delivery model.³⁸ We also included interventionists with diverse mental health training and backgrounds to enhance the scalability of BMT-CARE. Most studies have exclusively used psychologists to deliver behavioral interventions. Given that all transplant centers have access to either psychology or social work to support patients undergoing HCT and their caregivers, BMT-CARE has promising potential for scalability in this population. While prior caregiver interventions have focused exclusively on allogeneic HCT recipients,^16-18 we chose to include caregivers of autologous and allogeneic HCT recipients given the similarities in the HCT trajectory and acute post-HCT recovery period to ensure the generalizability of our findings to the larger transplant population.

Despite the prolonged caregiving process required for HCT,^{12, 14, 39} BMT-CARE led to improvement in both QOL and caregiving burden with medium effect sizes. Although prior caregiver interventions have shown reductions in stress and psychological distress among caregivers of HCT recipients, no studies demonstrated improvement in caregiver-reported QOL or caregiving burden.^16-18 Improvements in both QOL and caregiving burden are notable given the intense care demands of HCT recipients, the chronic nature of caregiving in this population, and the critical need to address caregiving burden as a major contributor to caregiver moral exhaustion and morbidity.^12-15

We also demonstrate the preliminary efficacy of BMT-CARE for improving anxiety and depression symptoms, as well as caregivers’ self-efficacy and coping skills, with medium to large effect sizes. Prior studies of caregiver interventions have demonstrated reduction in caregiver psychological distress. ^{16-18, 38}Enhancing caregivers’ self-efficacy and coping skills may be a key factor in reducing caregiver psychological distress and their perceived caregiving burden.^40-42 In fact, caregiving preparedness and self-efficacy may also lead to improvement in patient health behaviors such as adherence to complex post-HCT medical regimens.⁴³ Future studies to examine the effect of BMT-CARE on patient outcomes and to explore potential mediators of the intervention effects on caregivers’ psychological distress, and caregiving burden are warranted.

This study has several notable limitations. First, it was conducted at a single, tertiary care academic center with limited sociodemographic diversity, thereby limiting the generalizability of our findings to other care settings and caregivers of other races and ethnic backgrounds. Second, the study staff and participants were not blinded to randomization, which may have introduced bias. The RA collecting participant-reported outcomes was also not blinded to randomization. Although prior studies have suggested low-risk of bias with self-reported assessments,^{44, 45} nonetheless this is an important study limitation. Third, we did not collect long-term follow-up data to assess the sustainability of the intervention effects on caregiver-reported outcomes. Fourth, despite randomization, there were some baseline differences in caregiver-reported outcomes between the two groups, likely due to the relatively small sample size of this study. Intervention participants reported slightly worse baseline caregiver-reported outcomes. Nonetheless, we controlled for baseline differences in all of our analyses. Fifth, we did not assess the impact of the BMT-CARE intervention on patient outcomes. Sixth, we are unable to ascertain in this small feasibility study whether the intervention delivery modality impacts caregiver-reported outcomes.

In conclusion, a brief multimodal psychosocial intervention for caregivers of autologous and allogeneic HCT recipients tailored to the HCT trajectory is feasible and has promising preliminary efficacy for improving caregiver QOL, caregiving burden, anxiety and depression symptoms, as well as self-efficacy and coping skills. A future multi-site trial is needed to assess the impact of this potentially scalable intervention on long-term patient and caregiver outcomes and to explore potential mediators and moderators of intervention effects on these outcomes.