New Classification of Chronic Graft Versus Host Disease: Added Clarity from the Consensus Diagnoses.

Chronic graft versus host disease (CGVHD) is classically defined as occurring more than 100 days after hematopoietic cell transplant (HCT). But, with newer donor types and transplant strategies being used [eg. non myeloablative (NMA) and reduced intensity conditioning (RIC)] the presentation of the syndrome is changing. Clinical syndromes resembling acute GVHD (aGVHD) are often recognized beyond 100 days after HCT; possibly misdiagnosed as CGVHD. Additionally, the old grading system of limited versus extensive GVHD was designed to identify patients likely to benefit from systemic immune suppression and does not capture the severity of organ involvement. The Diagnosis and Staging Working Group of the NIH Consensus Development Project on Criteria for Clinical Trials in chronic graft-versus-host-disease proposed criteria for diagnosis and assessment of overall CGVHD severity. We retrospectively reviewed 197 patients who underwent sibling donor transplant between January 2002 to December 2005 to assess the applicability of the new criteria in predicting survival and transplant related mortality (TRM). Fifty four patients were diagnosed with CGVHD [cumulative incidence 28% (95% CI 22–34%)]. Of these, 8 [cumulative incidence 4% (95% CI 2–6%)] were reclassified as Late aGVHD; 31 [cumulative incidence 16% (95% CI 11–21%) had classic CGVHD and 15 [cumulative incidence 8% (95% CI 5–11%] had Overlap syndrome. Forty six patients with Overlap syndrome and classic CGVHD were graded. Six patients (13%) had Mild, 29 (63%) Moderate and 11 (24%) Severe CGVHD. After a median follow up of 35 months (range 4.3–59.2mo), 3 year probability of overall survival was significantly worse in Late aGVHD [25%(95% confidence interval 4–56%)] as compared to Overlap [87%(56–96%)] or CGVHD [75%(54–87%), p=0.001].). Amongst patients with Overlap and CGVHD (n = 46), similar survival was seen between mild or moderate disease. However, patients with severe disease had a trend to worse survival. [Mild-moderate 3 year probability of survival 85% (68–94%) versus Severe 57%(21–82%)]. Additonally, 3 year cumulative incidence of TRM was higher in patients with Late aGVHD [38% (9–67%)] versus Overlap syndrome [13%(0–27%)] or CGVHD [7%(0–13%)], p= 0.003. A trend towards greater TRM was seen in patients with severe GVHD [18%(0–36] versus mild+ moderate GVHD [6%(0–14%)]. This analysis indicates that the consensus guidelines are applicable to related donor HCT recipients and more reliably predicts survival and TRM than older classification of CGVHD. Prospective validation and testing in alternative donor cohorts is still needed before widespread acceptance is justified.