Incidence and Outcome of Chronic Graft-Versus-Host Disease (cGVHD) Using National Institute of Health (NIH) Criteria.
Authors: Jagasia Madan , Giglia J. , Chinratanalab W. , Chen H. , Dixon S. , Frangoul H. , Engelhardt B. , Goodman S. , Greer J. , Kassim A. , Morgan D. , Ruffner K. , Schuening F. 
Published: October 2019

Abstract
BACKGROUND: cGVHD, defined as GVHD after day 100 from allogeneic stem cell transplant (SCT), is a common complication, with impact on morbidity and survival. cGVHD has been previously classified as limited or extensive using Glucksberg criteria, which have not been reproducible or prognostic for late non-relapse mortality (NRM). Recently the NIH consensus criteria were proposed, but the ability of this classification to predict outcome of various subtypes of cGVHD is unknown.
HYPOTHESES:
Do various subtypes of GVHD affect overall survival (OS) or NRM in patients (pts) with GVHD after day 100 from SCT? Is the NIH severity scale sensitive to change in cGVHD? Does the NIH severity scale predict OS or NRM?
METHOD: Pts undergoing their 1st SCT for a hematological malignancy from 1/2001 and 12/2003 were studied. 110 pts alive beyond day 100 after SCT met criteria for the retrospective study, and excluded pts who recieved donor lymphocyte infusion or a 2nd SCT. GVHD after day 100 was classified using NIH consensus criteria as follows: persistent acute GVHD (aGVHD) (assigned at day 100), recurrent aGVHD, delayed aGVHD, classic cGVHD, overlap GVHD (all assigned at time of onset). Severity scores were assigned to pts with classic and overlap GVHD at onset and peak. Survival was measured as OS from time of transplant and time of onset of GVHD. Cumulative NRM was also computed.
RESULT: 37 (34%) had no GVHD and 73 (66%) pts had GVHD. The OS was 44% vs. 66% (no GVHD vs. GVHD, P=0.026). Time to death was shorter in pts without GVHD (0.73 yrs vs. 1.27 yrs, P=0.002). Of the 73 pts with GVHD, 14 (19%) had limited and 59 (80%) had extensive cGVHD. Pts with limited GVHD were reclassified as persistent aGVHD (1, 7%), recurrent aGVHD (4, 29%), and classic cGVHD (9, 64%).Pts with extensive cGVHD were reclassified as persistent (2, 3%), delayed (2, 3%), recurrent (18, 31%), classic chronic (22, 37%) and overlap GVHD (15, 26%). 31 (42%) had no worsening and 42 (58%) pts had worsening of GVHD. 65% of pts with classic cGVHD (22/31) had worsening compared to other types (20 of 42, 47%) (P=0.046). Severity score increased in 12 of 31 pts (39%) who had clinical worsening of GVHD (kappa coefficient=0.31). The OS of pts with various types of GVHD as proposed by the NIH criteria were significantly different (P<0.0001). This was more apparent when pts with any acute features of GVHD were compared to classic cGVHD (3-yr OS 47% vs. 66%, P=0.0015). This effect persisted even when survival was measured from onset of GVHD (P=0.0336). Severity at onset or peak of GVHD activity in pts with classic and overlap GVHD did not impact the survival. The 3-yr NRM (with relapse as a competing risk) for the entire cohort was 21% and was not affected by presence or absence of GVHD, or subtypes of GVHD. Significant variables using Cox model with time dependent covariates were any aGVHD feature after day 100 (HR 5.273, P=0.0004), and extensive cGVHD (HR 0.284, P=0.0041).
CONCLUSION: The OS with different NIH subtypes of GVHD after day 100 from SCT varies and is superior for pts with classic cGVHD. Global severity score may be useful as a descriptive clinical indicator of morbidity and the need for immunosuppressive therapy, but within the limits of our study, this score has no prognostic value with respect to survival and did not change with clinical worsening of GVHD.