Abstract
Background:
Patients undergoing allogeneic (allo) and autologous (auto) hematopoietic cell transplantation (HCT) require extensive hospitalizations or daily clinic visits for the duration of their transplant. Home HCT, wherein patients live at home and providers make daily trips to the patient’s residence to perform assessments and deliver any necessary interventions, may enhance patient quality of life and improve outcomes.
Objectives:
We conducted the first study of home HCT in the United States to evaluate this model in the US healthcare setting and to determine the effect on clinical outcomes and quality of life.
Study Design:
This case-control study evaluated patients who received home HCT at Duke University in Durham, NC from November 2012 to March 2018. Each home HCT patient was matched with two controls from the same institution who had received standard treatment based on age, disease, and type of transplant for outcomes comparison. Clinical outcomes were abstracted from electronic health records and quality of life was assessed via FACT-BMT. Clinical outcomes were compared with student’s t-test or Fisher’s exact test (continuous variables) or chi-square test (categorical variables). Quality of life scores were compared using the student’s t-test. All analyses used a significance threshold of 0.05.
Results:
25 patients received home HCT, including 8 allos and 17 autos. Clinical outcomes were not significantly different between the home HCT patients and their matched controls; home HCT patients had decreased incidence of relapse within one year of transplant (Table 1). Pre-HCT quality of life was well-preserved for autologous home HCT patients.
Conclusion(s):
This Phase I study demonstrated that home HCT can be successfully implemented in the United States. There was no evidence that home HCT outcomes were inferior to standard-of-care treatment, and patients undergoing autologous home HCT were able to maintain their quality of life. A Phase II randomized trial of home vs. standard HCT is currently underway to better compare outcomes and costs.
Keywords: hematopoietic cell transplantation, home-based, quality of life
Introduction
Each year in the United States, approximately 20,000 individuals undergo autologous or allogeneic hematopoietic cell transplantation (HCT), often requiring weeks to months-long hospitalization and conferring significant treatment-related morbidity and mortality1–5. Before stem cell engraftment, patients experience a period of neutropenia in which they are vulnerable to infection; despite current safeguards, rates of bloodstream infections occur in 20–45% of the hospitalized peri-HCT population2,6–12. HCT patients also report decreased quality of life and substantial out-of-pocket costs throughout the transplant process, with many continuing to experience financial challenges multiple years after transplant13–16.
In an attempt to reduce the rate of nosocomial infections and improve patient quality of life, several transplant centers have begun to allow their inpatients increased freedom to leave their hospital rooms at will, while others have established outpatient transplant programs where patients live near the hospital and make daily visits to the transplant clinic17–20. Although the move from inpatient hospitalization to outpatient day programs has many benefits, this approach places significant financial, emotional, and time burdens on caregivers who are often responsible for transportation logistics21,22.
Another option, home HCT, has been trialed at the Karolinska Institute in Sweden and may provide the optimal approach to minimizing transplant complications and maximizing patient quality of life23,24. In this approach, patients receive pre-HCT conditioning and stem cell infusion in a medical setting and are immediately discharged to their home on post-HCT Day 1. Providers (such as physicians, advanced practice providers, and/or registered nurses) make daily trips to the patient’s residence to perform a physical exam, draw labs, and deliver any needed interventions, such as blood transfusions or electrolyte supplementation. In a series of case-control studies conducted by the Karolinska Institute, allogeneic home HCT patients were discharged earlier than their standard care counterparts and also exhibited increased caloric intake, lower rates of acute graft-versus-host disease (GVHD), improved treatment-related mortality, and decreased medical costs23–27. Notably, standard-of-care at the Karolinska institute involves spending the entirety of the peri-transplant course inpatient, whereas the American approach incorporates outpatient day programs that allow patients to live at home and commute to clinic.
Inspired by this approach, we conducted the first study of home HCT in the United States to evaluate this model in the US healthcare setting and to determine the effect on clinical outcomes and quality of life.
Methods
Selection of Home HCT Patients:
This Phase 1 study includes patients who received home HCT at Duke University, Durham, NC from November 2012 to March 2018 and matched controls from the same institution. Aside from the care environment, all other clinical protocols (prophylactic antibiotics, frequency of visits, etc.) were identical in the two groups. Patients were required to be between the ages of 18 and 80 years, able to read and write English, live within a 90-minute driving distance of the medical center, and have a caregiver or team of caregivers for the duration of the stem cell transplant and recovery. Patients that did not have a caregiver, had a documented active infection prior to transplant, or used homeopathic medications or probiotics that could impact the gut microbiota were excluded from the study. Criteria for selection of home HCT patients were applied uniformly to the entire Duke cohort, with enrollment done on a first-come, first-serve basis as permitted by staffing bandwidth. This study was approved by the Duke Health System Institutional Review Board and was registered on ClinicalTrials.gov (NCT01725022).
Selection of Matched Controls:
To evaluate the safety of home HCT, participant clinical outcomes retrospectively were compared to that of a matched control cohort of patients, including both autologous and allogeneic transplant recipients, who underwent standard-of-care HCT during the study timeframe. Transplants were not matched by year but occurred during the same period from November 2012 – March 2018. These patients also required 24/7 caregiver support as this is standard-of-care for HCT at the study institution. Two matched controls were selected for each home HCT patient from a pool of patients transplanted during the same period who were enrolled in our IRB-approved biorepository. Logistic regression models were used to create a pool of multiple standard care patients for each home HCT patient. Autologous patients were matched by age, gender, and disease. Allogeneic patients were matched by age, gender, disease, donor type, and conditioning regimen intensity. Matched controls did not undergo home inspection, as this is not standard-of-care practice at our institution.
Home and Standard of Care HCT:
Patients eligible for home HCT underwent home inspection prior to the study to confirm cleanliness and suitability (e.g., absence of black mold, functional heating and cooling, clean water source). If the home was found to be suitable, they proceeded with home HCT. They would receive conditioning chemotherapy +/− irradiation followed by stem cell infusion in either the hospital or day clinic. The patient would then be discharged home on post-HCT Day 1 unless other medical conditions (e.g., sepsis, hypotension) required them to stay in the hospital.
A typical day at home would include a morning visit from an advanced practice provider (nurse practitioner or physician assistant). A full physical exam would be performed, and labs drawn and taken to the hospital for processing. If interventions were warranted, a nurse would return to the home in the early afternoon to deliver appropriate care based on the morning’s assessment and laboratory results (e.g., intravenous electrolyte supplementation, red blood cell or platelet transfusion, etc.). Patients would then videoconference (FaceTime or Jabber) with the attending physician. Patients were asked to return to the day clinic if they were receiving a red blood cell or platelet transfusion for the first time at our institution, administration of methotrexate or cyclophosphamide for graft-versus-host disease prophylaxis, removal of a Hickman catheter, or for any fever. If a patient required inpatient treatment or if the home was no longer suitable, the study participant would be admitted to the hospital. Daily follow up in the home would continue until the patient was discharged from the acute HCT phase to continue their care in the regular return clinic.
Patients who underwent standard-of-care HCT during this time also received their conditioning regimen followed by stem cell infusion in either the hospital or day clinic. They would either remain inpatient until engraftment or live in a local residence and make daily trips to the HCT clinic.
Clinical Outcomes and Definitions:
Clinical outcomes and demographic data were abstracted via queries of the Duke Adult Blood and Marrow Transplant database, automated chart review using the Duke Enterprise Data Unified Content Explorer for information not in the database, and manual review of electronic medical records for information not available through automated chart review. The following outcomes were collected for the home HCT patients and their matched controls: mortality, relapse, percent time hospitalized (defined as days in the hospital divided by days from start of HCT to discharge from acute peri-HCT care), days to engraftment, days to discharge from acute peri-HCT care, incidence of febrile neutropenia, days of febrile neutropenia, incidence and severity or acute and chronic graft-versus-host disease (GVHD) (in allogeneic HCT patients), clinically-significant bloodstream infection, laboratory-confirmed bloodstream infection (LCBI), mucosal barrier injury-laboratory confirmed bloodstream infection (MBI-LCBI), respiratory infection, Clostridioides difficile infection, and clinically-significant cytomegalovirus infection (csCMV). All infection variables were calculated for two time periods: “peri-transplant” (from the start of conditioning until discharge from the transplant phase) and “within the first year post-transplant” (from the start of conditioning until one year after stem cell infusion). Days to engraftment was defined as the number of days from stem cell infusion until neutrophil engraftment, the first of three consecutive days with absolute neutrophil count > 500. Febrile neutropenia was defined as fever (temperature > 38°C) occurring in a patient with less than 1500 neutrophils per microliter of blood28. Acute and chronic GVHD were scored based on internationally recognized scoring systems as described in the National Institutes of Health Chronic GVHD Diagnosis and Staging Consensus Working Group29,30. LCBI was defined as the presence of ≥1 positive blood cultures of a known pathogen or ≥2 positive and independently-drawn blood cultures of a common commensal with corresponding clinical symptoms per Centers for Disease Control/National Health Safety Network (CDC/NHSN) criteria31. MBI-LCBI was defined as an LCBI with an enteric organism associated with mucosal barrier injury disease per the CDC/NHSN31. The variable “clinically-significant bloodstream infection” includes both laboratory-confirmed bloodstream infections and infections deemed significant by the treatment team but that did not meet CDC/NHSN criteria (e.g., a febrile patient with only one positive culture of a common commensal but in whom there was a high clinical suspicion of bloodstream infection and who improved with a full course of antibiotic treatment was deemed to have a clinically significant bloodstream infection). Respiratory viral infection was defined as having a positive result on a respiratory viral panel testing for rhinovirus, parainfluenza, human metapneumovirus, adenovirus, respiratory syncytial virus, or influenza A or B. Clostridioides difficile infection was defined as a positive C. difficile PCR with corresponding symptoms of diarrhea. csCMV was defined has the detection of CMV DNA by PCR necessitating antiviral therapy with or without end-organ involvment32.
Quality of Life Data Collection:
The validated Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) survey was used to assess quality of life in home HCT patients at Day 0 (stem cell infusion), Day 30, Day 60, and Day 100 post-transplant33.
As matched controls were not collectively enrolled in a study that tracked similar quality of life measures, we compared these metrics between our home HCT patients and a previously described cohort undergoing standard-of-care HCT from 2010–201334,35. Quality of life data for this historical standard-of-care group was obtained for Day 0 and Day 100 post-transplant.
Statistical Analysis:
For comparison of clinical outcomes, continuous variables were compared using a t-test, while categorical variables were compared via the chi-square test or Fisher’s exact test. For comparison of quality-of-life metrics, FACT-BMT survey scores were compared within groups at various timepoints using the student’s t-test. Change of scores from baseline were also compared between groups (home vs standard-of-care) at Day 30, Day 80 and Day 100 using the student’s t-test. All analyses used a significance threshold of 0.05.
Results
Patient Demographics:
25 patients received home HCT, including 8 (32%) allogeneic HCT patients (allos) and 17 (68%) autologous HCT patients (autos). The oldest patient receiving home HCT was 74 years old. The median travel time to Duke was 26 minutes. Three home HCT autos had a pre-transplant Karnofsky Performance Status (KPS) score of 70, indicating that they were unable to carry on normal daily activities. There were no significant differences between the home HCT and matched control groups in demographics or baseline HCT characteristics, including pre-transplant KPS score and disease status (Table 1a, Table 1b, Table 1c). The most common indication for allo HCT in both the home and matched control patients was acute leukemia, while the most common indication for auto HCT was multiple myeloma.
Table 1a.
Combined Patient Demographics and Baseline Characteristics
| Home HCT (N=25) | Matched Controls (N= 50) | P-value1 | |
|---|---|---|---|
| Median Age (range) | 58 (29–74) | 58 (20–76) | 0.85 |
| Gender (female) | 9 (36%) | 22 (44%) | 0.51 |
| Race | 0.53 | ||
| White | 21 (84%) | 38 (76%) | · |
| Black | 4 (16%) | 10 (20%) | · |
| Other | 0 (0%) | 2 (4%) | · |
| Ethnicity (non-Hispanic) | 25 (100%) | 49 (98%) | · |
| Karnofsky Performance Status | 0.62 | ||
| 80 or below | 13 (52%) | 12 (48%) | · |
| 90–100 | 29 (58%) | 21 (42%) | · |
P-values obtained via t-test or Chi-square test.
Table 1b.
Allogeneic Patient Demographics and Baseline Characteristics
| Home HCT (N=8) | Matched Controls (N= 16) | P-value1 | |
|---|---|---|---|
| Median Age (range) | 45.5 (29–63) | 50.5 (23–72) | 0.87 |
| Gender (female) | 5 (62.5%) | 7 (43.8%) | 0.39 |
| Race | 0.99 | ||
| White | 6 (75%) | 12 (75%) | · |
| Black | 2 (25%) | 3 (18.8%) | · |
| Other | 0 (0%) | 1 (6.3%) | · |
| Ethnicity (non-Hispanic) | 8 (100%) | 16 (100%) | · |
| Karnofsky Performance Status | 0.68 | ||
| 80 or below | 3 (37.5%) | 8 (50%) | · |
| 90–100 | 5 (62.5%) | 8 (50%) | · |
| Disease | 0.45 | ||
| Acute leukemia (AML+ALL)2 | 5 (62.5%) | 10 (62.5%) | · |
| Lymphoma (HL+NHL)3 | 1 (12.5%) | 0 (0%) | · |
| MDS/MPN4 | 2 (25%) | 6 (37.5%) | · |
| Disease Status | 0.56 | ||
| First Complete Remission | 4 (50%) | 7 (43.8%) | · |
| 2nd or greater CR5 | 0 (0%) | 3 (18.8%) | · |
| Partial Remission | 1 (12.5%) | 0 (0%) | · |
| Active | 1 (12.5%) | 3 (18.8%) | · |
| Stable | 2 (25%) | 3 (18.8%) | · |
| Myeloablative Conditioning | 7 (87.5%) | 15 (93.8%) | 0.57 |
| HLA Matching6/Donor Type | 0.99 | ||
| MUD7 | 1 (12.5%) | 2 (12.5%) | · |
| MRD8 | 6 (75%) | 11 (68.8%) | · |
| MMRD9 | 1 (12.5%) | 3 (18.8%) | · |
| MMUD10 | 0 (0%) | 0 (0%) | · |
| Stem Cell Source | 0.99 | ||
| Peripheral blood | 7 (87.5%) | 12 (75%) | · |
| Bone marrow | 1 (12.5%) | 3 (18.8%) | · |
| Cord blood | 0 (0%) | 1 (6.3%) | · |
| GVHD11 Prophylaxis | 0.89 | ||
| CNI/MMF12 | 0 (0%) | 1 (6.3%) | · |
| CNI/MTX13 | 5 (62.5%) | 10 (62.5%) | · |
| PTCy14 | 1 (12.5%) | 3 (18.8%) | · |
| Other | 2 (25%) | 2 (12.5%) | · |
| T Cell Depletion | 1 (12.5%) | 3 (18.8%) | 0.99 |
P-values obtained via t-test or Chi-square test.
Acute Leukemia: acute myeloid leukemia + acute lymphoblastic leukemia.
Lymphoma: Hodgkin Lymphoma + Non-Hodgkin Lymphoma.
MDS/MPN: Myelodysplastic Syndrome/ Myeloproliferative Neoplasm.
CR: Complete Remission.
HLA: Human Leukocyte Antigen.
MUD: Matched Unrelated Donor.
MRD: Matched Related Donor.
MMRD: Mismatched Related Donor.
MMUD: Mismatched Unrelated Donor.
GVHD: Graft-Versus-Host Disease.
CNI/MMF: Calcineurin Inhibitor/ Mycophenolate mofetil.
CNI/MTX: Calcineurin Inhibitor/ Methotrexate.
PTCy: Post-transplant Cyclophosphamide.
Table 1c.
Autologous Patient Demographics and Baseline Characteristics
| Home HCT (N=17) | Matched Controls (N=34) | P-value1 | |
|---|---|---|---|
| Median Age (range) | 60 (46–74) | 61.5 (20–76) | 0.68 |
| Gender (female) | 4 (23.5%) | 15 (44.1%) | 0.15 |
| Race | 0.80 | ||
| White | 15 (88.2%) | 26 (76.5%) | · |
| Black | 2 (11.8%) | 7 (20.6%) | · |
| Other | 0 (0%) | 1 (2.9%) | · |
| Ethnicity (non-Hispanic) | 17 (100%) | 33 (97.1%) | 0.20 |
| Karnofsky Performance Status | 0.99 | ||
| 80 or below | 10 (58.8%) | 21 (61.8%) | · |
| 90–100 | 7 (41.2%) | 13 (38.2%) | · |
| Disease | 0.77 | ||
| Plasma Cell Dyscrasia | 11 (64.7%) | 20 (58.8%) | · |
| Lymphoma (HL+NHL)2 | 6 (35.3%) | 14 (41.2%) | · |
| Disease Status | 0.62 | ||
| First Complete Remission | 3 (17.6%) | 11 (32.4%) | · |
| 2nd or greater CR3 | 4 (23.5%) | 6 (17.6%) | · |
| Partial Remission | 10 (58.8%) | 17 (50%) | · |
| Stem cell source | 0.99 | ||
| Peripheral blood | 17 (100%) | 33 (97.1%) | · |
| Bone marrow/Peripheral blood | 0 (0%) | 1 (2.9%) | · |
P-values obtained via t-test or Chi-square test.
Lymphoma: Hodgkin Lymphoma + Non-Hodgkin Lymphoma.
CR: Complete Remission.
The 50 matched controls included 16 allos and 34 autos. 22 patients received inpatient care, while 28 received outpatient care.
HCT Course:
Clinical outcomes for home HCT patients and their matched controls are compiled in Tables 2a, 2b, and 2c. The home HCT cohort spent, in aggregate, 60.3% of their days entirely at home (without visiting the hospital or transplant clinic). Home HCT patients spent a median of 21% of their days in the hospital while their matched controls spent a median of 27% of their days in the hospital (p=0.36). Home HCT allos averaged significantly fewer clinic visits during transplant course compared to their matched controls (14.6 vs. 47.4, p=<0.001); this was also true for autos (5 vs. 12.3, p=<0.001). Home HCT allos spent an average of 17.8 days in the hospital, compared to 25.1 hospital days for matched controls (p=0.28). Home HCT autos averaged 4.6 hospitalized days, compared to 3.7 for matched controls (p=0.92).
Table 2a.
Combined Patient Outcomes
| Home HCT (N=25) | Matched Controls (N=50) | P-value1 | |
|---|---|---|---|
| Mean Number of Clinic Visits (IQR) | 8.1 (3–10) | 23.5 (13.3–30.5) | <0.001 |
| Mean Days Hospitalized (IQR) | 8.9 (1–10) | 11.3 (0–17) | 0.44 |
| Mean Percent Time Hospitalized (IQR) | 21% (4%–32%) | 27% (0%–40%) | 0.36 |
| Median Days to Engraftment (IQR) | 13 (12–16) | 12 (11–17) | 0.92 |
| Incidence of Febrile Neutropenia | 16 (64%) | 38 (76%) | 0.28 |
| Median Days of Febrile Neutropenia (IQR) | 7.5 (4.75–9.25) | 5 (3.25–10.75) | 0.91 |
| Clinically-Significant BSI2 Peri-Transplant | 7 (28%) | 8 (16%) | 0.22 |
| LCBI3 Peri-Transplant | 6 (24%) | 5 (10%) | 0.16 |
| MBI-LCBI4 Peri-Transplant | 2 (8%) | 4 (8%) | 0.99 |
| Respiratory Infection Peri-Transplant | 3 (12%) | 5 (10%) | 0.99 |
| C. difficile Infection Peri-Transplant | 0 (0%) | 4 (8%) | 0.29 |
| Clinically-Significant BSI2 1 Year Post-Transplant | 8 (32%) | 9 (18%) | 0.17 |
| LCBI3 1 Year Post-Transplant | 7 (28%) | 5 (10%) | 0.09 |
| MBI-LCBI4 1 Year Post-Transplant | 2 (8%) | 4 (8%) | 0.99 |
| Respiratory Infection 1Year Post-Transplant | 5 (20%) | 6 (12%) | 0.49 |
| C. difficile Infection 1 Year Post-Transplant | 0 (0%) | 6 (12%) | 0.17 |
P-values obtained via t-test, Fisher’s exact test, or Chi-square test.
BSI: Bloodstream Infection.
LCBI: Laboratory-Confirmed Bloodstream Infection.
MBI-LCBI: Mucosal Barrier Injury Laboratory-Confirmed Bloodstream Infection.
Table 2b.
Allogeneic Patient Outcomes
| Home HCT (N=8) | Matched Controls (N=16) | P-value1 | |
|---|---|---|---|
| Mean Number of Clinic Visits (IQR) | 14.6 (9.5–17.8) | 47.4 (34.8–51.3) | <0.001 |
| Mean Days Hospitalized (IQR) | 17.8 (6.5–22) | 25.1 (16.8–37.3) | 0.28 |
| Mean Percent Time Hospitalized (IQR) | 21% (8%–24%) | 26% (16%–36%) | 0.52 |
| Median Days to Engraftment (IQR) | 16 (16–19) | 18.5 (16.5–24) | 0.22 |
| Median Days to Discharge (IQR) | 92.5 (72–93.5) | 86 (83–111.5) | 0.21 |
| Incidence of Febrile Neutropenia | 5 (62.5%) | 11 (68.8%) | 0.99 |
| Median Days of Febrile Neutropenia (IQR) | 13 (9–14) | 16 (11–18) | 0.29 |
| Incidence of Acute GVHD2 | 0.52 | ||
| Grade A | 1 (12.5%) | 4 (25%) | · |
| Grade B | 4 (50%) | 3 (18.8%) | · |
| Grade C | 0 (0%) | 1 (6.3%) | · |
| Grade D | 1 (12.5%) | 1 (6.3%) | · |
| Incidence of Chronic GVHD2 | 0.83 | ||
| Mild | 2 (25%) | 2 (12.5%) | · |
| Moderate | 1 (12.5%) | 3 (18.8%) | · |
| Severe | 0 (0%) | 0 (0%) | · |
| Clinically-Significant BSI3 peri-Transplant | 2 (25%) | 4 (25%) | 0.99 |
| LCBI4 Peri-Transplant | 2 (25%) | 3 (18.8%) | 0.99 |
| MBI-LCBI5 Peri-Transplant | 1 (12.5%) | 2 (12.5%) | 0.99 |
| Respiratory Infection Peri-Transplant | 3 (37.5%) | 3 (18.8%) | 0.36 |
| C. difficile Infection Peri-Transplant | 0 (0%) | 2 (12.5%) | 0.54 |
| csCMV6 peri-Transplant | 3 (37.5%) | 6 (37.5%) | 0.99 |
| Clinically-Signiiicqnt BSI3 1 Year Post-Transplant | 3 (37.5%) | 5 (31.3%) | 0.99 |
| LCBI4 1 Year Post-Transplant | 3 (37.5%) | 3 (18.8%) | 0.36 |
| MBI-LCBI5 1 Year Post-Transplant | 1 (12.5%) | 2 (12.5%) | 0.99 |
| Respiratory Infection 1 Year Post-Transplant | 4 (50%) | 4 (25%) | 0.36 |
| C. difficile Infection 1 Year Post-Transplant | 0 (0%) | 4 (25%) | 0.26 |
| csCMV6 1 Year Post-Transplant | 3 (37.5%) | 6 (37.5%) | 0.99 |
| Relapse 1 Year Post-Transplant | 2 (25%) | 7 (43.8%) | 0.66 |
| Mortality 1 Year Post-Transplant | 2 (25%) | 5 (31.3%) | 0.99 |
P-values obtained via t-test or Chi-square test.
GVHD: Graft-Versus-Host Disease.
BSI: Bloodstream Infection.
LCBI: Laboratory-Confirmed Bloodstream Infection.
MBI-LCBI: Mucosal Barrier Injury Laboratory-Confirmed Bloodstream Infection.
csCMV: Clinically-Significant CMV.
Table 2c.
Autologous Patient Outcomes
| Home HCT (N=17) | Matched Controls (N=34) | P-value1 | |
|---|---|---|---|
| Mean Number of Clinic Visits (IQR) | 5 (2–8) | 12.3 (11–16) | <0.001 |
| Mean Days Hospitalized (IQR) | 4.6 (0–8) | 3.7 (0–8.8) | 0.92 |
| Mean Percent Time Hospitalized (IQR) | 21% (0%–33%) | 27% (0%–41 %) | 0.10 |
| Median Days to Engraftment (IQR) | 12 (12–13) | 11 (11–12) | 0.07 |
| Median Days to Discharge (IQR) | 19 (16–23, | 16.5 (14–18) | 0.004 |
| Incidence of Febrile Neutropenia | 11 (64.7%) | 27 (79.4%) | 0.31 |
| Median Days of Febrile Neutropenia (IQR) | 5 (4–7) | 4 (3–5) | 0.22 |
| Clinically-Significant BSI2 Peri-Transplant | 5 (29.4%) | 4 (11.8%) | 0.14 |
| LCBI3 Peri-Transplant | 4 (23.5%) | 2 (5.9%) | 0.09 |
| MBI-LCBI4 Peri-Transplant | 1 (5.9%) | 2 (5.9%) | 0.99 |
| Respiratory Infection Peri-Transplant | 0 (0%) | 2 (5.9%) | 0.55 |
| C. difficile Infection, Peri-Transplant | 0 (0%) | 2 (5.9%) | 0.55 |
| Clinically-Significant BSI2 1 Year Post-Transplant | 5 (29.4%) | 4 (11.8%) | 0.14 |
| LCBI3 1 Year Post-Transplant | 4 (23.5%) | 2 (5.9%) | 0.09 |
| MBI-LCBI4 1 Year Post-Transplant | 1 (5.9%) | 2 (5.9%) | 0.99 |
| Respiratory Infection 1 Year Post-Transplant | 1 (5.9%) | 2 (5.9%) | 0.99 |
| C. difficile Infection 1 Year Post-Transplant | 0 (0%) | 2 (5.9%) | 0.55 |
| Relapse 1 Year Post-Transplant | 0 (0%) | 7 (20.6%) | 0.08 |
| Mortality 1 Year Post-Transplant | 0 (0%) | 2 (5.9%) | 0.55 |
P-values obtained via t-test or Chi-square test.
BSI: Bloodstream Infection.
LCBI: Laboratory-Confirmed Bloodstream Infection.
MBI-LCBI: Mucosal Barrier Injury Laboratory-Confirmed Bloodstream Infection.
Reasons for hospitalization for the home HCT allos varied from mucositis (n=3, 37.5%), headache (n=1, 12.5%), GVHD (n=1, 12.5%), febrile neutropenia (n=1, 12.5%), and pleural effusion (n=1, 12.5%). Matched allogeneic transplant recipient controls generally remained in the hospital through engraftment and would return for bacteremia (n=4, 25%) or pain (n=3, 18.8%). Among autologous transplant recipients, fever was the leading indication for hospitalization for both home HCT (n=5, 62.5%) and matched control (n=8, 50%) patients.
Clinical outcomes:
There were no significant differences in incidence of febrile neutropenia, bloodstream infection, respiratory infection, or C. difficile infection during the peri-HCT period between the cohort of all home HCT patients and their matched controls. By one-year post-HCT, home HCT patients exhibited trends toward lower rates of C. difficile infection (0% vs 12%, p=0.17), and higher rates of LCBI (28% vs 10%, p=0.09) compared to their matched controls. (Table 2a).
Further analysis by transplant type revealed no significant differences between home HCT allos and their matched controls in median time to discharge from transplant phase, acute or chronic GVHD or in clinically significant bloodstream infection, LCBI, MBI-LCBI, respiratory infection, C. difficile infection, csCMV between groups during either the peri-transplant period or when tracked up to 1 year following transplant (Table 2b). There was also no difference between groups in 1-year relapse or mortality (Table 2b).
For autos, the median time to discharge from peri-transplant care for patients treated at home was 19 days versus 16.5 days for their matched controls (p=0.004). Among autos, there were no significant differences in clinically significant bloodstream infection, LCBI, MBI-LCBI, respiratory infection, C. difficile infection, or csCMV between groups during either the peri-transplant period or when tracked up to 1 year following transplant (Table 2c). None of the home HCT patients had relapsed disease within 1 year of transplant compared to 7 (20.6%) matched controls having relapsed disease within 1 year of transplant, though this difference was not statistically significant (p=0.08).
Quality of Life:
Quality of life was assessed via the FACT-BMT. A greater FACT-BMT score indicates a higher self-reported quality of life rating. The home HCT autos (n=11) did not experience a significant peri-transplant change in mean FACT-BMT; however, their mean score at Day 100 is significantly greater than their initial score at Day 0 (119.5 vs 108.3, p=0.001, Figure 1). Allo HCT data was not compared, as there were too few patients (n=2) who completed quality of life surveys at all necessary timepoints.
Figure 1.
Quality of life scores for autologous home HCT patients from Day 0 (stem cell infusion) until 100 days post-transplant: The mean quality of life score for home HCT autologous patients (n=11) does not significantly change until Day 100, at which point it is significantly greater than the FACT-BMT average at Day 0 (119.5 vs 108.3, p=0.001).
FACT-BMT scores were also compared between the autologous HCT patients who completed the FACT-BMT (n=11) and a previously described cohort of standard care patients (n=70) that underwent HCT during the same timeframe34,35. There was no significant difference in mean FACT-BMT at the start of transplant between home HCT and standard care patients (Figure 2). However, by Day 100, the mean FACT-BMT score of the home HCT autos was significantly greater than that of the standard care cohort (119.5 vs 104.7, p=0.016).
Figure 2.
Quality-of-life comparison between autologous home HCT patients (n=11) and historical controls (n=70): Mean FACT-BMT scores were not different between autologous home HCT or standard care patients at Day 0 (p=0.15). Home HCT autologous patients exhibited significantly higher scores at Day 100 compared to the standard care group (119.5 vs 104.7, p=0.016).
Discussion
While the sample size was small, this Phase I study demonstrated that home HCT can be successfully implemented in the United States, and there was no evidence that home HCT outcomes were inferior to standard-of-care treatment.
There was no difference in acute graft-versus-host disease (aGVHD) between groups. The Karolinska Institute has reported decreased aGVHD in their home HCT patients; however, the Karolinska standard care cohort spent the entirety of their transplant course in the hospital, whereas our matched controls only spent 26% of their days in the hospital due to our outpatient transplant program24,25. Thus, a difference might have been noted had our matched controls been hospitalized for a greater duration of their transplant, during which time they might have experienced increased hospitalization-related effects, such as disruption of the gut microbiota36.
For autos, median time to discharge was longer for home HCT patients than for their matched controls. Of note, “time to discharge from peri-transplant care” refers to the time in which the patients were actively followed by the transplant team and required to be near the transplant center. Therefore, the autologous home group did not spend more time in the hospital than matched controls; rather, they were followed by the care team for a longer period. This may have been due to increased time to engraftment in the home group, or extra precaution toward this group on the part of the transplant team.
Patients undergoing HCT experience impaired physical function, symptoms of anxiety and depression, and increased fatigue which can contribute to decreased quality of life37. In this study, home HCT autos experienced a significant increase in quality of life from their Day 0 baseline by Day 100, which has not been previously reported in the literature for standard-of-care treatment (Figure 2)38,39. Home HCT autos also reported higher quality of life scores at Day 100 compared to the standard care cohort (Figure 1), suggesting that home HCT care contributes to enhanced quality of life following HCT. This could be due to increased satisfaction, decreased financial burden, or improved medical outcomes. These data align with testimonials from our patients praising the home HCT program. They appreciate the ability to work from home, engage in their normal daily activities, and avoid costs associated with relocation to an apartment or the hospital.
Two phase 2 randomized controlled trials are currently underway to compare home HCT vs standard care treatment in allogeneic and autologous HCT recipients (NCT03667599, NCT02218151). These studies will include larger populations to power comparisons of clinical outcomes, gut microbiota, skin microbiota, and medical costs. Additional quality of life assessments will also be administered to evaluate the impact of home HCT on sleep, cognitive function, depression, anxiety, fatigue, and physical function. As healthcare utilization increases and hospitals run out of space40, home HCT holds great potential as a way to deliver high-quality care while improving patients’ quality of life and minimizing time spent in healthcare facilities. This may have particular importance during pandemics such as COVID-19, when keeping patients out of the hospital both protects patients and minimizes the burden on hospital resources41.
Highlights:
This case-control study confirmed viability of home HCT model at our institution.
Patient outcomes were comparable between the home and standard groups.
Autologous home HCT recipients had preserved quality of life throughout transplant.
Acknowledgements
We would like to thank the Duke Home HCT nurses, advanced practice providers, and physicians for their excellent work. We also acknowledge our collaborators Olle Ringden, Britt-Marie Svahn, and Stephan Mielke at the Karolinska Institute for their advice regarding the establishment of a home HCT program. Supported by grants from the National Cancer Institute (R01 CA203950-01, to ADS, NJC, AB, and LB; P30 CA008748 to Duke Cancer Institute), the National Heart, Lung, and Blood Institute (1R01HL124112, to ADS), the National Center for Advancing Translational Science (KL2 TR001115-03 to ADS), the National Institute of Aging and Duke Claude D. Pepper Older Americans Independence Center (2P30AG028716-11 Mini #6, to ADS), and Seres Therapeutics (to ADS).
Footnotes
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Financial Disclosure Statement
TC participates on the Speaker’s Bureau for Janssen Biotech. The other authors declare no conflict(s) of interest.
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