Patients who stay in their own familiar home environments during hematopoietic stem cell transplantation (HSCT) maintain a healthier gut microbiome than patients who undergo traditional inpatient HSCT, according to findings from a new phase 1 study. As a result, patients who undergo home HSCT have a better quality of life and a lower risk of adverse transplant outcomes.
Anthony D. Sung, MD, on behalf of his research team at the Duke Cancer Institute, described the home HSCT protocol at the American Society of Hematology's 59th Annual Meeting & Exposition, December 9 to 12, 2017, in Atlanta, GA.
Loss of bacterial diversity in the gastrointestinal tract increases the risk of transplant-related mortality. Changes in the predominance of specific populations of bacteria also influence outcomes. Domination of intestinal Enterococcus can cause enterococcal bacteremia, whereas the preservation of organisms such as Blautia reduces the risk of graft-versus-host disease (GVHD).
Multiple factors can alter the gut microbiome in patients undergoing HSCT, including conditioning chemotherapy, radiation therapy, antibiotic prophylaxis, diet, and change in environment, notably exposure to inpatient units and outpatient clinics.
"Traditionally we put our transplant patients in the hospital—what we think of as a protective environment," Sung said. "But taking patients out of their homes and putting them into alternate environments such as the hospital may cause significant disruption to their microbiome," he added.
Sung and his team at Duke focused on stabilizing the patient's environment by providing transplant services at home. The phase 1 study enrolled patients who were candidates for HSCT, lived within a 30-minute drive from the transplant center at Duke, and passed a home inspection to verify post-transplant safety (eg, the absence of black mold).
The home HSCT protocol was designed to keep patients at home for the duration of transplant. All patients underwent standard transplant conditioning chemotherapy as an inpatient or outpatient but were discharged home after receiving their infusion of stem cells.
After patients were discharged home, a typical day would include a morning house call by an advanced practice provider (nurse or physician assistant) for a full assessment, examination, and blood draw. The provider would then return to the hospital, and the patient's blood sample would be processed. Next, a nurse would make an afternoon house call, bringing home blood transfusions, intravenous antibiotics, fluids, and/or electrolytes, as indicated by results from the morning's assessment and blood test results. During the house call, the nurse could facilitate a video conference with an attending physician if needed.
Patients returned to the hospital for any events that could not be safely managed at home, such as febrile neutropenia. Patients also returned to the hospital for routine scheduled procedures, such as GVHD prophylaxis with methotrexate or the first blood transfusion to monitor for infusion reactions. Stool samples were collected at baseline, weekly for the first 4 weeks, and at days 60, 100, and 180 to assess changes in the gut microbiome.
To date, 22 patients undergoing autologous (n = 16) or allogeneic (n = 6) transplant have completed the home HSCT protocol. The median patient ages in the autologous and allogeneic groups were 60 years (range, 46-74 years) and 52 years (range, 34-63 years), respectively. Approximately two-thirds of patients had a Karnofsky Performance Status of 70 or 80 at baseline. Patients in the autologous group most commonly had multiple myeloma (62%) or non-Hodgkin lymphoma (38%), whereas those in the allogeneic group were more likely to have leukemia (67%). The patient's spouse was the primary caregiver in 75% to 83% of cases.
Results support the feasibility of keeping patients at home for a substantial portion of the transplant process (Table). Patients in the autologous and allogeneic groups spent 48% and 67% of their transplant days at home, respectively. More than one-third of patients spent 75% or more of their days at home. Febrile neutropenia was the most common reason for patients in the autologous (n = 9) and allogeneic (n = 4) groups to return for inpatient or outpatient care. The rates of bacteremia and GVHD were low relative to standard HSCT protocols. There was 1 case of treatment-related mortality involving GVHD in a patient post-allogeneic HSCT.
TABLE. Clinical Outcomes Associated With Home Transplantation
(n = 16)
(n = 6)
|Duration and Location of Transplant|
|Median duration (range)||18 days
|Median days at home, %||7.5 days (48%)||51 days (67%)|
|Median outpatient days, %||3 days (19%)||13 days (14%)|
|Median inpatient days, %||5 days (30%)||12 days (19%)|
|Patients spending > 75% of days at home, n (%)||6 (38%)||2 (33%)|
|Febrile neutropenia, n (%)||9 (56%)||4 (66%)|
|Bacteremia, n (%)||2 (13%)||2 (33%)|
|GVHD, n (%)||NA||3 (50%)|
|Treatment-related mortality, n (%)||0||1 (17%)|
GVHD = graft-versus-host disease; HSCT = hematopoietic stem cell transplantation.
Keeping patients at home appeared to maintain their gut microbiome or restore their biome after transplant. Relative to control data from patients undergoing standard HSCT, patients managed with the home HSCT protocol maintained greater microbiome diversity during and after transplant. Patients treated at home also avoided the typical domination of intestinal Enterococcus that occurs in the weeks following standard transplant.
Feedback on the home HSCT protocol was positive. "Patients and their caregivers endorsed the program, providing numerous expressions of appreciation and gratitude on exit interviews," Sung said. Favorable scores on quality-of-life measures reinforce the benefits of home care for transplant patients.
Based on positive findings from the phase 1 study, Sung and colleagues are planning a randomized phase 2 trial of home versus standard transplant in patients undergoing allogeneic HSCT. End points will include GVHD, infections, transplant-related mortality, biome diversity, and quality of life.
The team will also examine the impact of the home HSCT protocol on costs. "Keeping patients out of the hospital for even half the duration of transplant could have tremendous cost savings that would offset the increased staffing and travel required for house calls," Sung said.
Source: Sung AD, Nichols KR, Messina JA, et al. Hematopoietic stem cell transplantation at home. Presented at: American Society of Hematology 59th Annual Meeting; December 9-12, 2017; Atlanta, GA. Abstract 745.