What is the diagnostic approach for graft versus host disease (GVHD)?

Diagnostic Approach for Graft Versus Host Disease (GVHD)

The diagnostic approach for GVHD requires organ-directed biopsies of suspected sites combined with clinical assessment, laboratory testing, and imaging to rule out non-GVHD causes of symptoms. 1

Initial Evaluation

Clinical Assessment

• Skin manifestations: Assess for maculopapular rash, extent of body surface area involvement, bullous lesions
• GI tract symptoms: Document diarrhea volume, nausea, vomiting, abdominal pain
• Liver function: Monitor for hyperbilirubinemia and elevated liver enzymes
• Other symptoms: Evaluate for fever, lymphadenopathy (common in EBV-PTLD associated with GVHD) 1

Laboratory Testing

• Complete blood count with differential (monitor for cytopenias)
• Comprehensive liver function tests (bilirubin, transaminases, alkaline phosphatase)
• Viral studies to rule out viral reactivation (EBV, CMV)
• Stool studies to exclude infectious causes of diarrhea 1

Diagnostic Procedures

Tissue Biopsies

• Skin biopsy: First-line diagnostic procedure for cutaneous manifestations
• GI tract biopsies: Rectosigmoid biopsies have higher sensitivity and negative predictive value than other sites
  • Upper GI biopsy for nausea/vomiting
  • Lower GI biopsy for diarrhea
• Liver biopsy: Consider in patients with abnormal liver function tests without evidence of GVHD elsewhere 1

Imaging Studies

• CT scan or PET-CT to evaluate extent of disease involvement
• PET-CT particularly useful for staging EBV-PTLD associated with GVHD 1

Diagnostic Criteria

Acute GVHD

• Diagnosis based on clinical presentation and histopathologic findings
• Grading according to modified Glucksberg (consensus) criteria:
  • Skin: Stage 1-4 based on percentage of body surface area affected
  • Liver: Based on bilirubin levels
  • GI tract: Based on volume of diarrhea 1

Chronic GVHD

• Diagnosis requires at least one diagnostic manifestation of cGVHD or at least one distinctive manifestation plus confirmation by biopsy
• Bronchiolitis obliterans syndrome (BOS) requires pulmonary function tests and presence of cGVHD in another organ
• Grading according to NIH Consensus Development Project criteria 1

Special Considerations

Timing of GVHD

• Acute GVHD: Typically occurs within 100 days of transplantation
• Chronic GVHD: Usually develops within the first year but can occur years later 1

GVHD After CAR-T Cell Therapy

• GVHD can occur in patients who received CAR-T therapy after allogeneic hematopoietic cell transplantation
• Diagnosis follows standard protocols but must balance immunosuppression against CAR-T viability 1

EBV-Associated PTLD in GVHD

• Monitor EBV DNA-emia by quantitative PCR weekly starting within first month after transplant
• Continue monitoring for at least 4 months post-transplant
• Diagnostic workup includes physical examination, PET-CT/CT imaging, endoscopy for GI symptoms, tissue biopsy with EBER ISH and/or immunohistochemistry 1

Predictive Factors

Early immunologic recovery patterns may help predict GVHD development:

• Higher percentages of CD8+ T cells and lower fraction of CD56+ NK cells within 2 weeks of marrow infusion correlate with increased risk of grades 2-4 GVHD 2

Common Pitfalls to Avoid

1. Delayed diagnosis: Early recognition is critical as GVHD can progress rapidly
2. Misdiagnosis: Always rule out non-GVHD causes of symptoms (infections, drug toxicity, malignancy)
3. Incomplete assessment: All potentially affected organs should be evaluated
4. Relying solely on clinical features: Histopathologic confirmation is important when feasible
5. Inadequate monitoring: Regular follow-up is essential, especially in high-risk patients

Diagnostic Algorithm

1. Suspect GVHD based on clinical presentation and timing after transplantation
2. Rule out alternative diagnoses with appropriate tests
3. Obtain tissue biopsies from affected organs when feasible
4. Grade severity using standardized criteria
5. Monitor response to therapy using NIH Response Criteria

By following this systematic diagnostic approach, clinicians can ensure timely identification and appropriate management of GVHD, potentially improving morbidity, mortality, and quality of life outcomes for patients.