Abstract
Graft-versus-host disease (GVHD) is a complication following allogeneic hematopoietic cell transplant (allo-HCT) that frequently causes multiorgan affection and decrease in quality of life. Global assessment and care of these patients require a multidisciplinary approach, but access to focused clinics is limited given their scarcity and location in major cities, as well as mobility and transportation challenges that frequently affect these patients. Thus, we established a multispecialty GVHD telehealth (TH) clinic and hypothesized that a virtual platform will expand access to clinical care in children and adults. The clinic team members included BMT specialist, nursing, dermatologist, dentist, nutritionist, physiatrist, research personnel and others as needed. We evaluated all GVHD-related visits (in-person and TH) conducted in a single center from 01/2022 to 12/2022. Ninety-three patients received a total of 308 visits, and one-third were via TH. Approximately half of the in-person group had at least 1 TH visit, and 10 patients were seen exclusively via TH. Most patients had advanced chronic GVHD. More male patients were seen in GVHD clinic, but female patients had increased in clinic visits via TH (41% TH vs. 32% in-person). One-third of clinic visits were from patients of racial and ethnic minorities. While only 6% (n=12/217) of in-person visits were for patients living >100 miles from the center, 34% (n= 31/91) of TH visits were from far distances including out-of-state. At baseline, the most common patient-reported symptoms in a subset of patients included fatigue, disturbed sleep, and distress. Fifteen patients completed a follow-up symptom survey and reported significantly reduced distress regarding their GVHD (p= 0.02), although other symptoms remained stable. A multidisciplinary TH clinic provided care for adult and pediatric patients with GVHD. We demonstrated preliminary feasibility of building a robust TH platform with a collaborative multispecialty approach that allowed access and continuity of medical care. Gender inequalities were reduced, and distance to our center represented a lesser barrier to attending specialized care via TH. Additionally, patients reported a significant reduction in distress. Our findings support the ongoing development of a virtual platform to improve access to specialized GVHD care.
Keywords: GVHD, telehealth
INTRODUCTION
Graft-versus-host disease (GVHD) is a complex immune-mediated complication that frequently develops after allogeneic hematopoietic stem cell transplantation (allo-HCT)1,2 and can affect multiple organs, including skin, mouth, musculoskeletal system, gastrointestinal tract, and lungs, among others3-5. Therapy for GVHD, particularly systemic corticosteroids, can further contribute to complications such as infection and poor bone health6,7. While global assessment and care of these patients require a multispecialty approach8, access to focused clinics that can provide such care is limited given their scarcity and location in major cities, as well as mobility and transportation challenges that frequently affect patients with advanced GVHD9,10. Access to adequate medical care was further limited during the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak, declared a worldwide pandemic. In the U.S., a National Emergency was declared, and the Federation of State Medical Boards waived in-state licensure requirements for telehealth visits.
At Memorial Sloan Kettering Cancer Center (MSK), patients scheduled for GVHD-focused clinic visits had their appointments postponed or canceled. We, thus, proposed to establish a multispecialty GVHD telehealth clinic to expand access to specialized GVHD care. We hypothesized that a telehealth platform will provide continuity of patient care with a more diverse population of people affected by GVHD.
METHODS
Patients
Patients included in the analysis were children and adult allo-HCT recipients who were assessed for signs and/or symptoms of GVHD in-person or via telehealth platform by the GVHD clinic care team provider(s) at MSK between 01/01/2022 and 12/31/2022. The patient’s distance to the center from their primary residency or location at time of the clinic visit, including out-of-state location was assessed. The analysis was approved by the institutional review board.
GVHD Clinic Guidelines and Patient-Reported Outcome
A patient resource guideline was developed to assist the virtual clinic visit. The institutional Patient Education Committee reviewed and approved all the patient-related documents. A total of 4 guidelines were developed tailored to adults and children, which included an introduction to the GVHD clinic (Supplemental File 1) with a description of the GVHD clinic care team, instructions about the completion of the food and drink journal and digital patient-reported outcome measures (PROMs) surveys, what to expect during the day of the clinic visit, and post-clinic visit and follow-up; at-home medical photos guideline (Supplemental File 2A Adult, 2B Children) to include skin (face, arms, torso, and legs), mouth and lips, and range of motion (shoulder, elbow, wrist and fingers, and feet)11; stretching exercises in GVHD (Supplemental File 3) adapted for neck, back and extremities; and tips for managing GVHD such as skin care, makeup, physical activity and GVHD symptoms (Supplemental File 4).
A PROM questionnaire (M.D. Anderson Symptom Inventory - MDASI) evaluated the severity of symptoms experienced by patients with cancer and limitations in activities of daily living12. This questionnaire was adapted for children and adult patients with dynamically created checkboxes and radio buttons by the MSK e-Forms Committee. Each question included yes or no answer, and only if the former was selected, the question expanded to a scale of 0-10 (0= no symptom, 10= the worst possible in severity). An alert code red was set for severe pain, sadness, and shortness of breath with a scale of 8-10 whereas an alert code yellow was set for moderate symptoms of pain (score 7), drowsiness (score 8-10), and shortness of breath (score 6-7). If a patient had a severe or moderate response, an automatic message alert was sent to the primary medical team, monitored by nursing. This allowed nurses to follow up in real-time if needed. The link for completion of the questionnaire was shared with the patient at the time of GVHD clinic visit confirmation, approximately 1-5 days prior to their scheduled visit. During the assessment period, a total of 5 alerts code red were triggered (2 pain, 1 sadness, 2 shortness of breath) whereas 11 alerts code yellow were activated (3 pain, 5 drowsiness, 3 moderate shortness of breath). After the GVHD-RN assessment in real-time, further evaluation was escalated to the BMT clinician if clinically warranted. If a patient was unable to complete the questionnaire electronically, a paper version was provided if the clinic visit was conducted in person.
GVHD Telehealth Clinic Workflow
The in-person multispecialty GVHD clinic at MSK served as the clinic model for providers and participants. A virtual platform was implemented at the height of SARS-CoV-2 pandemic with the objective to expand access to specialized GVHD care in children and adults. The telemedicine platform was adapted for multi-provider use with simultaneous access. The MSK’s Digital Informatics & Technology Solution team (DigITs) developed the MSK Telemedicine platform in collaboration with Accenture, Avanade and Microsoft for integration of software capabilities. Patients were scheduled to the GVHD clinic using the TH platform when unable to attend in-person (e.g. transportation issues, lack of caregiver) or for continuity of care alternating with in-person visits.
A clinic workflow pre-, during, and post-visit was implemented (Figure 1). Before the patient’s multidisciplinary GVHD scheduled visit, a GVHD informational packet with a photo guide was provided electronically. Additionally, the patients had a link to the MDASI PROM survey12. During the visit day, the patients received a secured link to enter a virtual clinic room. A GVHD-trained nurse joined the visit for a dedicated GVHD evaluation and photo review for approximately 5-7 minutes. If photos were deemed inadequate, the nurse requested a retake. Alternatively, photos were obtained during the virtual visit as a screenshot if the patient allowed. Subsequently, a specialized provider(s) joined the visit either concurrently or consecutively with an approximate duration of 20-40 minutes. The GVHD team members included a BMT-GVHD specialist (adult or pediatric BMT) who coordinated the overall patient care, a GVHD-specialized dermatologist who conducted a dedicated skin evaluation, via both patient-taken clinical photographs and video exam, and addressed cutaneous and genital conditions, if applicable, a dentist who provided oral hygiene and care, a physiatrist who addressed limitations in mobility and activities of daily living through a dedicated review of systems and a focused evaluation including range of motion assessment11, and coordinated rehabilitation programs with physical therapy and/or occupational therapy as well as a nutritionist who evaluated the patient’s caloric intake and provided diet instructions. Additional providers were included on a case-by-case basis such as endocrinologist, ophthalmologist, gastroenterologist, and pulmonologist. Physicians-in-training (e.g., residents, fellows), interpreters, and other clinical team members could join the virtual appointment. At the end of the virtual visit, each provider summarized their recommendations to the patient. Post-visit, PROM questionnaire responses were collected, the research clinical assistant completed data collection, and the GVHD-trained nurse provided counseling and final instructions. Social worker assistance was utilized as a liaison with the local oncologist and provided information about patient support groups and other resources if needed. The average length of the multidisciplinary TH visit, including the post-visit care, was approximately 30-60 minutes. A subset of patients with GVHD-focused visits seen by the BMT-GVHD specialist alone were included in the analysis.
Figure 1. Multidisciplinary GVHD clinic workflow via telehealth.
The telehealth clinic workflow had three components of pre, during, and post- clinic visit. Multiple clinicians, social worker and research assistants were part of the team.
Study definitions
The Consensus Conference and MAGIC Criteria on Acute GVHD Grading guided aGVHD evaluation13,14; GVHD after day 100 with purely acute features was graded accordingly. Chronic GVHD was defined according to National Institutes of Health consensus criteria which were used to assess organ affection and severity of cGVHD3, and followed the institutional guidelines for review and adjudication of GVHD15. The distance of the patient’s location to the center was calculated using their reported zip code.
Statistical analysis
Descriptive statistics were used to summarize the data. At baseline and visit-related follow-up times, select measures from the MDASI for quality of life were assessed. Descriptive statistics summarized the baseline measurements, and the change from baseline when paired data were available was assessed using a Wilcoxon signed-rank test. Significance was assessed using a two-sided test at an alpha level of 0.05.
RESULTS
Patient demographics
All patients GVHD clinic visits (in-person, telehealth)
A total of 308 GVHD-related clinic visits for 93 individual patients were conducted in 12 months, and one-third (n= 91) were performed via TH (Table 1). The median number of visits per patient was 3 (range 1-11), and the median number of providers per patient was 1 (range 1-8), with an average of 2.5 providers per patient. The whole group had a median age of 50 years (range 4-81) with a median age for the adult clinic of 58 (range 25-81) and pediatric clinic of 14 years (range 4-25). Most of the clinic visits were for male patients (66%), which was similarly observed in the in-person clinic visits (68%). Approximately two-thirds of the clinic visits were for patients of White race, followed by White-Hispanic, Asian, Black (African American and Black Hispanic), and others.
Table 1.
Patient demographics for in-person and telehealth clinic visits
| GVHD clinic (IP & TH) (n= 308) |
GVHD clinic (IP) (n= 217) |
GVHD clinic (TH) (n= 91) |
|
|---|---|---|---|
| Median age, years (range) | 50 (4-81) | 50 (4-81) | 56 (4-73) |
| Adult clinic | 58 (25-81) | 57 (25-81) | 59 (25-73) |
| Pediatric clinic | 14 (4-25) | 12 (4-25) | 19 (4-25) |
| Male, n (%) | 202 (66%) | 148 (68%) | 54 (59%) |
| Race, n (%) | |||
| White | 203 (66%) | 134 (62%) | 69 (76%) |
| White-Hispanic | 31 (10%) | 19 (9%) | 12 (13%) |
| Asian | 23 (7%) | 18 (8%) | 5 (6%) |
| Black (AA/Hispanic) | 33 (11%) | 30 (14%) | 3 (3%) |
| Other | 18 (6%) | 16 (7%) | 2 (2%) |
| GVHD syndrome, n (%) | |||
| Acute GVHD | 5 (2%) | 5 (2%) | - |
| Persistent/recurrent aGVHD | 25 (8%) | 13 (6%) | 12 (13.3%) |
| Late aGVHD | 9 (3%) | 7 (3%) | 2 (2%) |
| Chronic GVHD | |||
| - Interrupted | 145 (47%) | 103 (48%) | 42 (46%) |
| - Progressive | 22 (7%) | 13 (6%) | 9 (10%) |
| - De novo | 55 (18%) | 43 (20%) | 12 (13.3%) |
| Overlap | 40 (13%) | 27 (12%) | 13 (14.3%) |
| No GVHD | 7 (2%) | 6 (3%) | 1 (1%) |
| GVHD syndrome, n (%) | |||
| Skin | 211 (69%) | 153 (71%) | 58 (64%) |
| Superficial sclerosis | 53 (25%) | 40 (26%) | 13 (22%) |
| Deep sclerosis | 158 (75%) | 113 (74%) | 45 (78%) |
| Oral | 68 (22%) | 44 (20%) | 24 (26%) |
| Eyes | 152 (49%) | 102 (47%) | 50 (55%) |
| Genitalia | 4 (1%) | 4 (2%) | 0 |
| GI | 63 (20%) | 49 (23%) | 14 (15%) |
| Liver | 0 | 0 | 0 |
| Lung | 38 (12%) | 33 (15%) | 5 (6%) |
| MSK | 99 (32%) | 77 (35%) | 22 (24%) |
| Range of motion, median (range) * | |||
| Shoulders | 6.5 (4-7) | 6.5 (4-7) | 7 (5-7) |
| Elbows | 7 (3-7) | 7 (5-7) | 7 (3-7) |
| Wrists | 6.5 (2-7) | 6.25 (2-7) | 7 (5-7) |
| Feet | 4 (2-4) | 4 (2-4) | 4 (2-4) |
| GVHD severity, n (%) | |||
| Grade 1-4 aGVHD | 25 (8%) | 19 (9%) | 8 (9%) |
| Mild | 44 (14%) | 28 (13%) | 16 (18%) |
| Moderate/Severe | 205 (67%) | 148 (68%) | 55 (60%) |
| No GVHD or quiescent | 34 (11%) | 22 (10%) | 12 (13%) |
| Proximity to center, n (%) | |||
| <25 miles | 115 (37.3%) | 90 (41%) | 23 (25%) |
| 25-50 miles | 109 (35.3%) | 81 (37%) | 28 (31%) |
| 51-100 miles | 43 (14%) | 34 (16%) | 9 (10%) |
| >100 miles | 41 (13.3%) | 12 (6%) | 31 (34%) |
Abbreviations: N, number; IP, in-person; TH, telehealth; AA, African American; GVHD, graft-versus-host disease; aGVHD, acute GVHD; GI, gastrointestinal.
Range of motion assessment in a cohort up to 171 cases.
Table 2 describes the disease and transplant characteristics in the 93 individual patients (72 adults, 21 pediatric). All patients were transplanted for the treatment of hematologic malignancies or advanced hematologic disorders. The most common malignant disease was acute leukemia and myelodysplastic syndrome, followed by lymphoma, and others. More patients received a reduced intensity or non-myeloablative conditioning. However, pediatric patients received predominantly myeloablative conditioning. Half of the patients had a matched-unrelated donor, followed by matched-related donor, and 21 (23%) patients received a haploidentical, cord blood or mismatched-unrelated donor. While most of the grafts were 8/8 HLA-matched from a peripheral blood stem cell source, pediatric patients had predominantly a bone marrow or cord blood graft. The most common GVHD prophylaxis was calcineurin inhibitor-based (CNI-based) and only 8 (9%) patients received post-transplant cyclophosphamide.
Table 2.
Patients’ disease and transplant characteristics
| Characteristic | Adult (IP) (n= 43) |
Adult (TH) (n= 35) |
Pediatric (IP) (n= 20) |
Pediatric (TH) (n= 7) |
|---|---|---|---|---|
| Diagnosis, n (%) | ||||
| Acute leukemia/MDS | 21 (49%) | 16 (45.7%) | 10 (50%) | 2 (29%) |
| Lymphoma | 15 (35%) | 16 (45.7%) | 1 (5%) | 1 (14%) |
| MM/CML/MPN/SCID/Other | 7 (16%) | 3 (8.6%) | 9 (45%) | 4 (57%) |
| Conditioning intensity, n (%) | ||||
| Myeloablative | 8 (22%) | 10 (28.5%) | 14 (70%) | 5 (71%) |
| Reduced intensity/NMA | 33 (74%) | 23 (66%) | 6 (30%) | 2 (29%) |
| Unknown | 2 (4%) | 2 (5.5%) | - | - |
| Donor, n (%) | ||||
| MRD | 14 (33%) | 10 (29%) | 3 (15%) | - |
| Related-haplo | 2 (5%) | 2 (5.5%) | 2 (10%) | 1 (14%) |
| MUD | 23 (53%) | 16 (45.5%) | 4 (20%) | 4 (57%) |
| MMUD* | 3 (7%) | 5 (14%) | 11 (55%) | 2 (29%) |
| Unknown | 1 (2%) | 2 (5.5%) | - | - |
| HLA match, n (%) | ||||
| 8/8 | 37 (86%) | 26 (74%) | 7 (35%) | 4 (57%) |
| <8/8 | 5 (12%) | 7 (20%) | 13 (65%) | 3 (43%) |
| Unknown | 1 (2%) | 2 (6%) | - | - |
| Stem cell source, n (%) | ||||
| PBSC | 37 (86%) | 27 (77%) | 4 (20%) | 1 (14%) |
| BM | 2 (4.7%) | 2 (6%) | 8 (40%) | 3 (43%) |
| CB | 2 (4.7%) | 3 (8.5%) | 8 (40%) | 2 (29%) |
| Unknown | 2 (4.7%) | 3 (8.5%) | - | 1 (14%) |
| GVHD prophylaxis, n (%) | ||||
| CNI (+/− MTX, +/− siro +/− other) | 34 (79%) | 30 (86%) | 16 (80%) | 6 (86%) |
| Siro/MMF/MTX | 1 (2.3%) | − (0%) | - | - |
| PTCY-based | 4 (9.3%) | 3 (8%) | 1 (5%) | 1 (14%) |
| T-cell depletion | 1 (2.3%) | 1 (3%) | 3 (15%) | - |
| Unknown | 3 (7%) | 1 (3%) | - | - |
Abbreviations: N, number; IP, in-person; TH, telehealth; MM, multiple myeloma; MDS, myelodysplastic syndrome; CML, chronic myeloid leukemia; MPN, myeloproliferative disorder; SCID, severe combined immunodeficiency; NMA, non-myeloablative; MRD, matched-related donor; MUD, matched-unrelated donor; MMUD, mismatched unrelated donor; HLA, human leukocyte antigen; PBSC, peripheral blood stem cell; BM, bone marrow, CB, cord blood; GVHD, graft-versus-host disease; CNI, calcineurin inhibitor; MTX, methotrexate; Siro, sirolimus; MMF, mycophenolate mofetil; PTCY, post-transplant cyclophosphamide.
Includes CB grafts
GVHD telehealth visits
Ninety-one TH visits for 42 individual patients were conducted in a 12-month period Table 1. The adult clinic had 78 visits (n= 35 patients) with a median age of 59 (range, 25-73), and the pediatric clinic had 13 visits (n= 7 patients), median age 19 (range, 4-25). The median number of TH visits per patient was 2 (range 1-9) whereas the median number of providers per patient was 1 (range 1-6), with an average of 1.96 per patient. Approximately half of the patients who had an in-person GVHD-related clinic visit utilized the TH platform. Notably, 10 patients (9 adults, 1 pediatric) were seen exclusively via the TH for a total of 17 visits. The gender distribution showed an increased number of clinic visits for female patients through TH when compared to in-person visits (41% TH vs. 32% in-person). Black patients had fewer clinic visits via TH (n= 3, 3%).
Patients seen via TH had a similar proportion of diagnoses of acute leukemia/myelodysplastic syndrome and lymphoma (Table 2). Most received reduced intensity or non-myeloablative conditioning except for the children who had myeloablative conditioning as the most used regimen. Similar to the in-person group, the majority received a matched related or unrelated donor allo-HCT from a peripheral blood stem cell graft, and GVHD prophylaxis was mainly CNI-based. Only 3 patients received PTCY-based and 1 patient had a CD34 selected graft.
GVHD Syndrome and Severity
Most of the cases seen in our multidisciplinary clinic had cGVHD (Table 1). Approximately half had cGVHD interrupted syndrome, followed by de novo cGVHD and overlap syndrome. The least common cGVHD syndrome was progressive cGVHD. Thirteen percent of the clinic visits (n= 39/308) had aGVHD features (5 aGVHD, 25 persistent or recurrent aGVHD, 9 late aGVHD). Notably, 7 visits had no GVHD diagnosis at the time of assessment. Organ involvement included the skin, followed by skin, eyes, musculoskeletal, oral, gastrointestinal, and lung. Notably, skin involvement was predominantly deep sclerosis (n= 158, 75%) whereas superficial involvement was observed less (n= 53, 255). Only four clinic visits demonstrated genitalia involvement and none of the cases had liver. Range of motion assessment in a cohort of patients demonstrated a wide range in mobility. Two-thirds of clinic visits were for patients with advanced moderate or severe cGVHD, and only 14% had mild cGVHD (n= 44/308), and 8% had grade 2-4 aGVHD (n= 25/308). Eleven percent of cases had quiescent symptoms or no GVHD.
The patients who were seen via TH had similar GVHD features to the overall group. Most cases had cGVHD, with cGVHD interrupted as the most common syndrome. Fifteen percent of the clinic visits were for patients with aGVHD features, mainly persistent or recurrent aGVHD. Organ involvement was similar to the overall group, with skin as the organ most commonly involved, followed by eyes, oral and musculoskeletal. No cases of genitalia and liver involvement were reported. Notably, the majority had advanced moderate or severe cGVHD, but cases with mild severity or not active GVHD (n= 28/91, 31%) used the TH platform as well. We evaluated the 10 patients see exclusively via TH and found that their median age was 58.5 years (range 16-73), 60% were male and most had acute leukemia/MDS (n= 9). The most common diagnosis was cGVHD interrupted (n= 6), followed by de novo cGVHD, overlap syndrome and persistent/recurrent aGVHD, 1 patient respectively. There was 1 patient with findings not consistent with GVHD. GVHD severity included 3 patients had no GVHD/quiescent, 4 with mild GVHD affecting the skin and/or mouth, whereas 3 had moderate/severe symptoms. The advanced cGVHD patients had multiorgan involvement including the skin (2 deep sclerosis, 1 superficial sclerosis), eyes (n= 3), lungs (n= 1), and musculoskeletal (n= 1). The patient with lung involvement had pulmonary function test performed locally. Most patients were White (n= 6), followed by Asian (n= 2), White Hispanic (n= 1) and Black (n= 1).
GVHD clinic visits and distance to the hospital
We calculated the distance from the patient’s current residence to our medical center. As expected, most clinic visits were for patients within a 0-50 miles radius of the center, which was similarly observed in the in-person clinic visits (Figure 2A). Only 6% (n= 12/217) of the clinic visits were for patients living >100 miles from MSK. In contrast, the TH platform had the largest proportion of visits from distant locations (>100 miles) (n=31/91, 34%, Figure 2B), including out-of-state locations such as Pennsylvania, Delaware, Florida, and Texas. Notably, patients living closer to the center at 0-50- and 51-100 miles radius used the TH platform as well.
Figure 2. Proximity to the medical center in miles. A. Clinic visits in-person, B. Clinic visits telehealth.
The proportion of clinic visits from far distance >100 miles increased with the telehealth platform.
Patient reported outcome measures (PROMs)
A subset of patients completed the PROM questionnaire MDASI for quality-of-life assessment. Fifty-two patients completed a baseline evaluation at the time of their initial visit to our GVHD clinic (Figure 3A). Overall, most patients reported multiple symptoms including pain, fatigue disturbed sleep and distress as well as having symptoms interfering with mood, work, relations with others and enjoyment of life. The reported symptoms with the highest median scores were fatigue and disturbed sleep whereas nausea and poor appetite were mild to no symptoms. Only 7 patients had no symptoms to report. A follow-up PRO questionnaire was obtained in a subset of 15 patients who returned to clinic at least once. Most symptoms remained stable except for distress which was significantly reduced (p= 0.02, Figure 3B).
Figure 3. The MDASI PROM questionnaire in a subset of patients. A. Baseline, B. Follow-up visit.
Patients reported multiple symptoms at the time of their medical visit. However, distressed was significantly reduced in a follow-up visit.
Discussion
GVHD is a life-threatening complication that frequently occurs after allo-HCT1,2,5,16-18. Patients affected by this complication require continued medical care and support4. Here, we evaluated the feasibility of building a robust GVHD clinic using a TH platform with a collaborative multispecialty approach that allowed continuity of care for adult and pediatric patients affected by acute and/or chronic GVHD. The TH platform served as an adjuvant to clinic visits that allowed frequent medical evaluations or served as the sole source of GVHD care. We observed that both adults and children utilized our TH platform. However, the utilization of the telehealth pediatric clinic was limited by a low number of patients with a higher median age. Patients with established care at MSK as well as elsewhere had access to our TH clinic. Our clinic workflow included specialists that addressed the most common complications in GVHD including dermatologist, dentist, physiatrist, nutritionist as well as BMT-GVHD specialist. Other providers were included on a case-by-case basis. Our digital platform was adapted to allow multi-provider type use for simultaneous access. Our digital GVHD informational packet with a photo guide was developed as an educational tool and navigation system for our clinic.
Our analysis included all adult and pediatric patients who had a GVHD-related visit in a 12-month period using both the in-person and TH platforms. Overall, we observed similar patients and transplant characteristics except for gender distribution. More male patients sought in-person medical care. Notably, this gap was narrowed by female patients who increased the use of the TH platform. While this observation requires further evaluation, we hypothesize that female patients have less access to healthcare because of logistical issues such as transportation, financial barriers, women’s roles as caregivers shifting to their spouses, and reliance on other family members with restricted availability4,9,19-21. Hence, access to the TH platform may have minimized gender inequality in access to GVHD healthcare.
The race distribution in our GVHD clinic was predominantly White, followed by White-Hispanic, Asian, and Black patients. Notably, we observed that the proportion of Black patients using the TH platform was lower when compared to in-person visits. A subset of our patients had limited access to smartphones or internet connectivity, which may have limited their virtual access. Thus, we utilized our social workers as an essential team member in our GVHD clinic to assist our patients. However, barriers to healthcare access for patients from racial and ethnic minorities require further evaluation22-24. We consider that further efforts in education and community outreach are needed as well.
As expected, most of our patients had advanced moderate to severe cGVHD. GVHD severity was not identified as a barrier for access to our TH platform as multiple patients with limited mobility or transportation were seen virtually, including at the peak of SARS-CoV-2 pandemic. Notably, patients with mild GVHD were seen in our clinic as well, who may benefit the most from early interventions to minimize the risk of further progression of their GVHD signs and symptoms16,25. However, our virtual platform limits our physical exam, such as evaluation of early skin sclerosis, which is relevant to prevent future morbid conditions26. Our clinic evaluated patients with acute GVHD, which is important to highlight since acute features can be present after day 1003, and patients should receive a dedicated review of systems, physical examination, and treatment despite their time post-HCT. Additionally, a subset of patients with quiescent GVHD or no GVHD were followed in our clinic. This continuity of care allowed treatment response assessment and therapy guidance for dose taper or treatment discontinuation.
Most clinic visits seen in our multidisciplinary GVHD clinic were from patients in proximity to our medical center and only a small proportion of patients from further distances sought in-person medical care. In contrast, a higher proportion of clinic visits of patients residing from further distances including out-of-state were seen through our TH platform. Notably, clinic visits from patients in close proximity to the medical center also occurred, which suggests that the TH platform can be used as a tool to access medical care for all patients. This is relevant because of the scarcity of multispecialty GVHD clinics for the care of adult and pediatric patients, and the healthcare system adapting to patients who return to their communities but still require dedicated multispecialty care or are relocating or traveling.
Our quality-of-life assessment showed that most patients reported multiple symptoms at baseline, and several had interferences with their life function including work, relations with others and life enjoyment. These findings were expected as GVHD can have a significant impact on QoL8,27-29. Notably, a subset of patients who completed a follow-up PROM survey showed stable symptoms except for a significant reduction in distress. However, this interpretation is limited by the small number of completed follow-up PROM surveys. We hypothesize that access to support and a specialized medical team contributes to the decrease in distress that is frequently seen in GVHD patients.
The findings above highlight that a multidisciplinary TH clinic provided care for adult and pediatric patients with GVHD, most with advanced disease. We demonstrated the feasibility of building a robust TH platform with a collaborative multispecialty approach that allowed continuity of care. Gender inequality was reduced, distance to our center represented a lesser barrier to attending specialized care, and patients reported a significant reduction in distress. Our findings support the ongoing development of a virtual platform to improve access to specialized GVHD care. Our model can be replicated by other medical centers to serve a wider underserved community24. Other medical centers in Miami and Chicago are adopting our clinic workflow. We want to highlight that while our results are encouraging and demonstrated feasibility, our findings need to be validated in a future larger prospective study. We plan to expand our multidisciplinary TH platform for the further support of patients with GVHD that can serve as a hybrid model of combined in-person and TH visits. Thorough in-person examinations are strongly recommended to detect early GVHD physical manifestations and accuracy of treatment response, particularly when skin deep sclerosis is present, as we predominantly observed in our patients. Collaboration with community health care providers and coordination of tests to be done locally such as bloodwork, radiology and pulmonary function tests are essential to optimize the care of GVHD patients that have access to the TH platform. Nonetheless, our efforts may be hampered due to the increasing medical licensing restrictions across state lines in the post-COVID era. Minimizing state licensing restrictions for physicians and advanced care providers who care for patients with rare diseases such as GVHD, can improve access to specialized medical care that is limited across the nation, particularly in rural and suburban areas. A collective effort in support of modernized healthcare access is urgently needed.
Supplementary Material
Highlights.
A telehealth platform with multidisciplinary approach was developed for GVHD care.
Female patients had increased visits via telehealth, reducing gender inequalities.
Increased proportion of patients from far distances were seen via telehealth.
Patients reported significant reduction in distress after attending GVHD clinic.
Our findings support the ongoing development of a virtual platform to improve access to specialized GVHD care.
ACNOWLEDGEMENTS
This study was supported by the Incyte Ingenuity Award in GVHD (2021 Award Recipient). The work was also supported by the Memorial Sloan Kettering Cancer Center Support Grant (P30 CA008748), and R01 HL164902-02. We would like to acknowledge the GVHD research team, nursing staff and advanced practice providers who greatly contributed to this work. We thank our patients and families for their support and contributions.
Footnotes
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CONFLICT OF INTEREST
A.C.H. serves as advisory board member and received honoraria from Incyte, Sanofi, y-mAbs Therapeutics, Janssen Scientific Affairs and Horizon Pharma. A.M. serves as a consultant for ADH Therapeutics, Alira Health, AstraZeneca, Blueprint Medicines, Protagonist Therapeutics, OnQuality, Sanofi, and Janssen, receives royalties from UpToDate, and research funding from Amryt Pharma, Incyte Corporation, Kintara Therapeutics, Novartis, Novocure. M.A.P. reports honoraria from Adicet, Allogene, Allovir, Caribou Biosciences, Celgene, Bristol-Myers Squibb, Equilium, Exevir, ImmPACT Bio, Incyte, Karyopharm, Kite/Gilead, Merck, Miltenyi Biotec, MorphoSys, Nektar Therapeutics, Novartis, Omeros, OrcaBio, Sanofi, Syncopation, VectivBio AG, and Vor Biopharma. He serves on DSMBs for Cidara Therapeutics and Sellas Life Sciences, and the scientific advisory board of NexImmune. He has ownership interests in NexImmune, Omeros and OrcaBio. He has received institutional research support for clinical trials from Allogene, Incyte, Kite/Gilead, Miltenyi Biotec, Nektar Therapeutics, and Novartis. D.M.P. serves as advisory board member for Incyte, Evive Biotechnology (Shanghai) Ltd Corporation and Sanofi, serves as consultant to CareDx and OncLive, and receives research funding from Incyte and Sanofi. Other authors have no conflicts of interest to declare.
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