ACUTE GRAFT Versus Host Disease 1990-2017: Reduced Incidence and Predictive Factors

Alessandra Di Francesco¹ , Anna Maria Raiola² , Alida Dominietto² , Carmen Di Grazia², Francesca Gualandi², Maria Teresa Van Lint², Patrizia Chiusolo^{1, 3}, Luca Laurenti^{1, 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.