ACUTE GRAFT Versus Host Disease 1990-2017: Reduced Incidence and Predictive Factors
Authors: Di Francesco Alessandra , Bacigalupo Andrea 
Published: November 2019

Alessandra Di Francesco1 , Anna Maria Raiola2 , Alida Dominietto2 , Carmen Di Grazia2, Francesca Gualandi2, Maria Teresa Van Lint2, Patrizia Chiusolo1, 3, Luca Laurenti1, 3, Federica Sora'1, 3, Sabrina Giammarco1 , Elisabetta Metafuni1 , Emanuele Angelucci2 , and Andrea Bacigalupo
,3
1Istituto di Ematologia, Fondazione Policlinico Universitario A Gemelli IRCCS, Roma Italy
2IRCCS Policlinico San Martino, Genova, Italy
3Universita' Cattolica del Sacro Cuore, Roma, Italy;
Background: Acute Graft versus Host Disease (GvHD) is a major complication of allogeneic HSCT, and prophylaxis has significantly changed in time .
Aim of th study: we wanted to determine the cumulative incidence of GvHD and its outcome, in 3 periods :<2000; 2000-2010; >2010, together with predicting factors.
Methods: we analyzed 3126 patients allografted in 2 transplant Centers between 1976 and 2018. Median age increased over the 3 periods from 32 (1-66) to 42 years (9-71) to 50 years (range13-74) (<0.00001).
Results
GvHD timing : The median day of onset of GvHD before year 2000 was day +14 (2-90), between 2001 and 2010 it was day +19 (2-98) and beyond year 2010 it was day +33 (2-98) (p<0.0001). There were 237 patients developing GvHD before day 14 before year 2000, 71 patients between 2001 and 2010 and only 8 patients beyond 2010 (p<0-0001).
GvHD cumulative incidence. The cumulative incidence (CI) of GvHD grade II-IV was 47% before 2000, 24% between 2000 and 2010, and 16% after 2010 (p<0.00001).
The CI of GvHD grade III-IV was 13%, 5%, 4% respectively in the three periods (p<0.001). Survival at 5 years of patients with GvHD grade II has remained unchanged in the 3 periods (52%, 44%, 55%, respectively , p=0.2); survival of patients with GvHD grade III-IV has improved from 15%, to 30% and 23% respectively (p=0.003).
GvHD and donor type. The incidence of GvHD grade II-IV in HLA identical siblings (SIBS) was 25%, 19% and 14% in the 3 periods (p=0.0005), and for alternative donors, these figures were 43%, 34%, 21% (p<0.00001).
Transplant related mortality (TRM). The CI of TRM for patients with grade II GvHD has not changed significantly (27%, 25%, 20%, p=0.1) whereas TRM for patients with GvHD grade III-IV has been reduced from 70% (<2000) to 49% (2001-2010) to 26% beyond year 2010 (p=0.002).
Multivariate analysis on survival for patients with grade II GvHD . Significant predictors of survival, for patients with GvHD grade II, were the day of onset of acute GvHD (</>day 14), advanced phase of the disease, transplant year before year 2000, patients age over 60, and a donor other than an HLA identical sibling. When adding together these negative predictors , the 5 year survival was 28% for patients with 3-5 negative predictors, as compared to 56% for patients with 0-2 negative predictors
Conclusions. We show a very significant reduction of the CI of GvHD with time, together with a very significant delay of the onset of the disease. TRM has been reduced in patients with grade III-IV GvHD, less so in patients with GvHD grade II. In the latter significant clinical predictors may allow the identification of patients at high risk, eligible for treatment protocols.

Disclosures
No relevant conflicts of interest to declare.