Despite the serious risk of morbidity and nonrelapse mortality that chronic graft-vs-host disease (cGVHD) presents to patients receiving hematopoietic cell transplantation (HCT), screening for manifestations of cGHVD remains inconsistent across US transplant centers, according to multicenter qualitative study on the topic published in Transplantation and Cellular Therapy.1 This finding is particularly concerning as transplant physicians have come to recognize the importance of early detection and prevention of cGVHD before the effects have permanent consequences across different organ systems in patients.
“Once these manifestations happen, it's really difficult to make them reversible, especially if they get picked up or detected late in the course,” Laila Alkhouli, MD, chief fellow in pediatric hematology/oncology and blood and marrow transplantation at Cleveland Clinic Children's in Cleveland, Ohio and first author of the study, said in an interview with Targeted OncologyTM.
This need for early intervention justified the study, conducted within the Engraft Learning Health Network (LHN), a multicenter collaborative of pediatric and adult HCT programs. Despite comprehensive frameworks and guidelines disseminated from the National Institutes of Health consensus criteria, Foundation for the Accreditation of Cellular Therapy (FACT), and Center for International Blood and Marrow Transplant Research (CIBMTR), Alkhouli and her colleagues sought to identify how real-world practice may differ. “The question we thought of is…how GVHD screening is actually being performed in real-world, daily clinical practice,” she said.
A Wide Range of Practice, Not Isolated Gaps
To answer that question, Alkhouli and colleagues conducted 33 structured interviews with clinician representatives across 10 Engraft LHN transplant centers, addressing assessment frequency, documentation, and organ-specific screening depth. “The main finding that we have is how much variability we found in terms of cGVHD screening,” she said. Only about half of respondents reported monthly screening in the first 6 months after day 100 posttransplant, and just 37% continued quarterly assessments beyond 1 year. The overall findings were not just about individual aspects lacking from a particular center’s practice, but the lack of a uniform approach to cGVHD screening across centers, Alkhouli observed.
cGVHD Screening by the Numbers
Based on 33 structured interviews across 10 Engraft Learning Health Network transplant centers:1
- 63% of respondents did not routinely discuss GU symptoms with male patients; 42% did not with female patients
- 37% continued quarterly cGVHD assessments beyond 1 year post-transplant, down from 52% who screened monthly in the first 6 months
- 12% performed comprehensive skin exams and 21% used structured skin scoring, despite universal review of skin symptoms
- 10% incorporated the Lee Symptom Scale, a validated patient-reported outcome measure, into routine documentation
- 0% reported a standardized or comprehensive oral cGVHD assessment; median clinician confidence identifying oral disease was 6 out of 10
- Fewer than 25% performed pulmonary function tests at intermediate intervals (9, 15, or 21 months), despite near-universal testing at the 1- and 2-year milestones
- Fewer than 10% routinely screened for rare manifestations, including neuropathy, cytopenias, eosinophilia, pleural/pericardial effusion, or immune dysregulation
That lack of uniformity extended to specific organ systems. Although skin symptoms were universally reviewed, comprehensive skin exams and structured cGVHD scoring were reported by only 12% and 21% of respondents, respectively. Alkhouli said that this was a good example of the issues they discovered; although most clinicians did ask about general skin symptoms such as dryness, itchiness, or new rashes, the lack of comprehensive examination could lead to missed signs of sclerotic features associated with poorer outcomes.
Alkhouri pointed to pulmonary function testing (PFT) as another area of “major variability,” noting that most centers tested at the 1- and 2-year milestones but inconsistently in between: a fewer than 25% of respondents reported PFTs at intermediate intervals such as 9, 15, or 21 months.
Why Early Detection of Chronic GVHD Matters
For Alkhouli, the stakes of that variability are what make the findings urgent. “Detecting cGVHD late is a major problem, because at that point, most of the manifestations—the damage—are already there, and the way back is really hard and difficult,” she said. “The changes are irreversible, and the risk of morbidity and high mortality from many manifestations, like pulmonary bronchiolitis obliterans, or fibrosis in the skin and in the joints—these are all irreversible manifestations.” Alkhouli and her coauthors cited findings that skin involvement affects up to 80% of patients with cGVHD, and even modest increases in epidermal disease burden have been independently associated with nonrelapse mortality.2
Translating Guidelines Into Daily Practice
When it comes to how screening practices are observed in common practice compared with a strict clinical trial, Alkhouli described a structural mismatch rather than a knowledge gap. “In a transplant clinic, physicians are busy most of the day dealing with competing issues,” she said. “These frameworks and guidelines are quite comprehensive, so outside of a clinical trial or a dedicated GVHD clinic, screening would be less structured or [more] provider dependent.” The study's oral cavity findings illustrate that mismatch: no respondents reported using a standardized or comprehensive oral assessment, and median clinician-reported confidence in identifying oral cGVHD was just 6 out of 10.1 “Having a practical tool that can take the important points from the guidelines and translate them into a streamlined, feasible process is the key,” Alkhouli said, “because cGVHD can start in a very subtle way.”
Genitourinary (GU) screening showed the starkest example of that gap, with 42% and 63% of respondents not routinely discussing GU symptoms with female and male patients, respectively. Alkhouli attributed this in part to discomfort on both the provider and patient sides of the exam room as several of the locations surveyed were pediatric centers. The discomfort in discussing these areas in younger patients could lead to less-than-comprehensive screening even though the GU organ systems can be affected seriously by cGVHD.
Why Chronic GVHD Screening Must Continue Beyond Year 1
Alkhouli also emphasized that screening needs to extend well beyond the first year posttransplant. “cGVHD screening must also be longitudinal, because we have new data now showing that new cGVHD can still happen even 1 to 2 years posttransplant,” she said, citing cGVHD Consortium data that reported new events beyond that window.3 “Transplant and cGVHD treatment are evolving. We [know] a lot more now, and early detection also must evolve. We don't just need to know if the patient has GVHD or doesn't—we want a systematic, structured process to screen and identify problems early, intervene early, and hopefully prevent bad complications.”
Building a Practical Screening Tool
Rather than framing the solution as stricter adherence to comprehensive guidelines, Alkhouli said the Engraft LHN is working toward something simpler. “We don't need to have a complex or complicated system to screen for cGVHD,” she said. “For providers, just having a systematic, structured way—comprehensive daily review of systems, focused but consistent physical exams, maybe a simple [electronic medical record (EMR)] tool or flow sheet or a dot phrase that they can use every day consistently with every patient—it’s as simple as that.” The network’s proposed next step is synthesizing existing guideline recommendations, including monthly screening for the first 6 months, quarterly assessment through year 2, and continued surveillance every 6 months thereafter, into a streamlined bundle for rapid-cycle implementation across centers.1
Patient and caregiver education is the other half of that equation, Alkhouli said. “We need to teach patients and caregivers about chronic GVHD symptoms—rashes, dryness, eye dryness, skin dryness, skin and joint stiffness, exercise intolerance—so they know to reach out to us earlier, rather than waiting for their next clinic appointment, which may be in 2 or 3 months.”
“Feasibility and consistency are important, rather than just complexity,” Alkhouli said. “Having a practical, feasible, streamlined tool and process that physicians can rely on in their daily clinical practice is the goal from all our work.” Beyond that, the long-term goal for cGVHD management is eventually “having earlier detection, earlier intervention, and hopefully improving outcomes of our transplant survivor population,” she concluded.
REFERENCES
1. Alkhouli L, Rotz S, Dandoy C, et al. Toward standardized screening for chronic graft-versus-host disease: insights from the Engraft Learning Network. Transplant Cell Ther. Published online 2026. doi:10.1016/j.jtct.2026.07.036
2. Baumrin E, Baker LX, Byrne M, et al. Prognostic value of cutaneous disease severity estimates on survival outcomes in patients with chronic graft-vs-host disease. JAMA Dermatol. 2023;159(4):393-402. doi:10.1001/jamadermatol.2022.6624
3. Pidala J, Onstad L, Carpenter P, et al. Longitudinal study of late acute and chronic graft-versus-host disease after allogeneic hematopoietic cell transplantation: a long-term follow-up study from the Chronic Graft-Versus-Host Disease Consortium. Transplant Cell Ther. 2026;32(2):205.e1-205.e12. doi:10.1016/j.jtct.2025.10.026
