The Importance of Adequate Symptom Assessment in Chronic Graft-Versus-Host Disease Management

Chronic graft-versus-host disease (cGVHD) remains a persistent cause of late morbidity and mortality in patients who have received an allogeneic transplantation. Rigorous, standardized symptom assessment should be the foundation of treatment decision-making.¹ Symptom assessment includes a structured, organ-by-organ evaluation coupled with a patient-reported symptom burden that is performed at baseline and at clinically meaningful intervals to guide treatment and tapering decisions.²  

Disease assessment requires grading organ function (0-3) of the skin, eyes, mouth, esophagus, upper and lower GI tract, liver, lungs, and joints and fascia, and genital tract assessment when applicable.²  Liver function tests to measure hepatic involvement, pulmonary function tests to assess for bronchiolitis, and photographic range-of-motion tools to assess for sclerotic disease should be utilized.² Global severity and the modified Lee Symptom Scale (LSS) scores should be recorded alongside organ function scores to capture symptom changes that impact patient care.^2.3 

Treatment options require precise phenotyping to match therapy to organ pattern, comorbidities, and patient tolerance; the current treatment landscape for GVHD is suited to this type of assessment.¹ Moreover, because steroid-refractory, steroid-dependent, and steroid-intolerant states warrant timely steroid-sparing strategies, assessment must also note corticosteroid toxicity and functional impact.² Practically speaking, that means not waiting for obvious progression when symptom burden persists or adverse effects from steroid therapy emerge, despite a nominal partial response by NIH criteria.² 

When systemic therapy beyond corticosteroids is required, approved treatments include a JAK inhibitor (ruxolitinib), a BTK inhibitor (ibrutinib), a ROCK inhibitor (belumosudil), and a CSF-1R inhibitor; Label-specified indications should guide sequencing and access.^3-5 Safety profiles for each product differ and should be considered at each assessment. Adverse reactions may include: cytopenias and infection with ruxolitinib; hemorrhage, infection, and cardiac events with ibrutinib; embryofetal toxicity and hemorrhage with belumosudil; and infusion-related reactions and musculoskeletal pain with axatilimab csfr.^3-5  

In conclusion, a checklist for clinical assessment should include: organ function scores, global severity score, modified LSS score, current steroid dose with toxicities, objective tests (eg, liver function tests), and a clear target or next visit, with a steroid response status explicitly assigned to trigger modification of therapy in a timely manner.² Such discipline shortens exposure to high-dose steroids, aligns escalation with patient-reported burden, and supports rational, class-balanced sequencing across approved treatment options.¹^,²  

References: 

1. Kovalenko I, Saleem T, Shah M, et al. Novel pharmacological treatment options of steroid-refractory graft-versus-host disease. Adv Hematol. 2023;2023:9949961. doi:10.1155/2023/9949961.
2. NCCN clinical practice guidelines in oncology (NCCN Guidelines®) for hematopoietic cell transplantation graft-versus-host disease. Version 1.2025.  
3. Teh C, Onstad L, Lee S, et al. Reliability and validity of the modified 7-day Lee chronic graft-versus-host disease symptom scale. Biol Blood Marrow Transplant. 2020;26(4):562-567. 
4. JAKAFI® (ruxolitinib). Prescribing Information. Incyte; 2023.  
5. IMBRUVICA® (ibrutinib). Prescribing Information. Pharmacyclics LLC; 2024.  
6. REZUROCK® (belumosudil). Prescribing Information. Sanofi; 2025.  
7. NIKTIMVO^TM (axatilimab-csfr). Prescribing Information. Incyte; 2025.