Acute graft versus host disease 1976-2020: reduced incidence and predictive factors

Alessandra Di Francesco; Anna Maria Raiola; Alida Dominietto; Carmen Di Grazia; Francesca Gualandi; Maria Teresa Van Lint; Stefania Bregante; Patrizia Chiusolo; Luca Laurenti; Federica Sora; Sabrina Giammarco; Elisabetta Metafuni; Alberto Fresa; Simona Sica; Emanuele Angelucci; Andrea Bacigalupo

doi:10.3389/fmed.2023.1320692

Acute graft versus host disease 1976-2020: reduced incidence and predictive factors

Front Med (Lausanne). 2024 Jan 24:10:1320692. doi: 10.3389/fmed.2023.1320692. eCollection 2023.

Authors

Alessandra Di Francesco¹, Anna Maria Raiola², Alida Dominietto², Carmen Di Grazia², Francesca Gualandi², Maria Teresa Van Lint², Stefania Bregante², Patrizia Chiusolo^{1

3}, Luca Laurenti^{1

3}, Federica Sora^{1

3}, Sabrina Giammarco¹, Elisabetta Metafuni¹, Alberto Fresa¹, Simona Sica^{1

3}, Emanuele Angelucci², Andrea Bacigalupo^{1

3}

Affiliations

¹ Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy.
² IRCCS AOU San Martino IST, Genova, Italy.
³ Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Università Cattolica del Sacro Cuore, Roma, Italy.

Abstract

We studied the incidence of acute graft versus host disease (GvHD) and its outcome in three consecutive time frames (year <2000; 2000-2010; >2010), in 3,120 patients allografted in two transplant Centers between 1976 and 2020. The median age increased over the three periods from 32 to 42 to 54 years (p < 0.00001). The median day of onset of GvHD in the three periods was day +14, day +16, and day +30, respectively (p < 0.0001). The cumulative incidence (CI) of GvHD grades II-IV in the three periods was 47, 24, and 16%, respectively (p < 0.00001). The CI of GvHD grades III-IV was 13, 5, and 4% (p < 0.001). In multivariate analysis, significant predictive factors for GvHD II-IV, on top of year of transplant, were anti-thymocyte globulin (ATG) (RR 0.67, p > 0.001); post-transplant cyclophosphamide (PTCY) (RR 0.41, p < 0.001), a family mismatched donor (RR 1.31, p = 0.03) a matched unrelated donor (RR 2.1, p < 0.001), an unrelated mismatched donor (RR1.8, p = 0.001), donor age above 40 years (RR 1.27, p < 0.001), hematological malignancy-as compared to aplastic anemia (RR 2.3, p < 0.001). When selecting only GvHD grade II, in a multivariate analysis, there was a significant reduction of transplant-related mortality (TRM) for patients grafted in 2001-2010 (RR 0.62, p < 0.0001) and for patients grafted in 2011-2020 (RR 0.35, p < 0.0001) as compared to grafts before the year 2000. A similar reduction in time was seen for patients with GvHD grades III-IV. The overall TRM in the three periods was 30, 22, and 16% (p < 0.0001) and survival was 47, 51, and 58% (p < 0.0001). Relapse risk was unchanged. In conclusion, we showed improved prevention of acute GvHD with time, together with a significant delay in the onset of the disease. Treatment of GvHD has also improved over time, as suggested by both reduced TRM and improved survival in more recent transplant periods.

Keywords: GvHD; acute GVHD; allotransplantation; hematology; transplant.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by Associazione Italiana Ricerca contro il Cancro (AIRC) grant to AB 2017.