Prophylaxis and Treatment of Graft Versus Host Disease After Allogeneic Stem Cell Transplantation: A Survey on Center Strategies by the European Group for Blood and Marrow Transplantation (EBMT)
Authors: Ruutu Tapani , van Biezen Anja , Hertenstein Bernd , Henseler Anja , Garderet Laurent , Passweg Jakob , Rocha Vanderson , Saccardi Riccardo , Sureda Anna , Gratwohl Alois , Niederwieser Dietger , de Witte Theo 
Published: October 2019

Abstract
Abstract 1261
Allogeneic stem cell transplantation is a poorly standardized treatment. Reported outcomes vary markedly, partly due to differences in treatment procedures. The EBMT performed a survey among its member centers about their present strategies in preventing and treating graft versus host disease (GvHD). Seventy-three centers from 23 countries participated in this survey. The main prophylactic regimens used in transplantations with myeloablative conditioning were cyclosporine (CsA) + methotrexate (MTX) in 83%, CsA + mycophenolate mofetil (MMF) in 14 %, tacrolimus (tacro) + MTX in 6%, CsA alone in 8%, and tacro alone, tacro + MMF and ex vivo T-cell depletion (TCD) in 1% of the centers. The administration of CsA was initiated on day -6 (1%), day -3 (13%), day -2 (7%), day -1 (78%) or day 0 (1%). CsA was initially given as short i.v. infusions in 56% (twice daily 91%), continuous infusion in 39% and orally in 5% of the centers. The initial CsA dose was most commonly 3 mg/kg/day (49%); 1–2,5 mg/kg/day was given in 16%, 4–6 mg/kg/day in 31%, and 10–12,5 mg/kg/day in 4% of the centers. Further doses were then usually adjusted according to CsA concentrations (88%), measured from whole blood (81%) or serum (19%). When measured from whole blood, the target CsA concentrations at 1 wk post-Tx ranged from 80 to 400 (mean 230) ng/ml, and at 2–4 wks and 2 mths the ranges (means) were 95–400 (210) and 60–350 (200) ng/ml, respectively. The typical duration of CsA prophylaxis was 60–100 (32%), 120–150 (10%), 180 (54%), or 210–365 (14%) days. In 56% of the centers the estimated risk of relapse affected the length of prophylaxis. MTX was given in the dose of 15 mg/m2 on day +1 and 10 mg/m2 on days +3, +6, and +11 in 63% and without the last dose in 28% of the centers. There were 6 other variants. Leucovorin rescue was given in 43% of the centers with variable dose and timing. ATG was included in the prophylaxis for one or more subgroups (one center all patients) in 79%, alemtuzumab in 25%, corticosteroids in 10%, and TCD in 24% (one center all patients) of the centers. The main prophylactic regimens in reduced intensity transplantations (RIC) were CsA + MMF (67%), CsA + MTX (33%), CsA (23%), in vivo TCD (19%), tacro + MMF (10%), ex vivo TCD (3%), and tacro alone and tacro + MTX (1% each). ATG was used in some groups of patients in 73% of the centers. The development of chimerism affected the intensity of prophylaxis in 82% of the centers. All centers used corticosteroids as first line treatment of acute GvHD. The treatment was started at first signs likely to be caused by GvHD (17%) or for grade II or higher (83%). The decision to treat was based on clinical signs only in 70% of the centers while in 30% histological documentation was needed. The corticosteroid of choice was methylprednisolone (83%) or prednisolone (17%). The initial daily dose/kg was 1-1, 5 mg (19%), 2 mg (76%), 3 mg (6%), 5–10mg (3%), or 20 mg (1%), given in 1 (16%), 2 (69%), 3 (9%) or 4 (6%) doses, i.v. (79%) or orally (21%). The severity of aGvHD affected the initial dose in 53% and the organ manifestation in 27% of the centers. The dose per kg/day indicating corticosteroid resistance and need for second line treatment was 1mg (3%), 2 mg (72%), 4–5 mg (13%), or 10 mg or more (12%). The minimum time to confirm corticosteroid resistance was 2 (2%), 3 (11%), 4–5 (27%), 6–7 (44%), 10–14 (13%) or 21 (3%) days. The most widely used second line treatments were MMF (33%), anti-TNF antibodies (31%), other monoclonal antibodies (16%), ATG (27%), extracorporeal photopheresis (ECP, 14%), mesenchymal stem cells (7%), alemtuzumab (7%), pentostatin (5%) and “keep going with corticosteroids” (12%). The initial treatment for newly diagnosed chronic GvHD in patients with no ongoing immunosuppressive treatment was corticosteroid (57%), calcineurin inhibitor (CNI) + corticosteroid (38%), or CNI alone (10%). The minimum duration of first line treatment of chronic GvHD to allow the evaluation of efficacy was 2 wks or less (21%), 2–4 wks (12%), 1 mth (42%), 1,5-4 mths (21%), or 9–12 mths (4%). The most commonly used second line treatments were ECP (53%), MMF (36%), rituximab (12%), CNI (12%), mTOR inhibitors (9%), corticosteroids (8%), and tyrosine kinase inhibitors (6%). In conclusion, the present results show marked differences between centers in the prophylaxis and management of GvHD. These findings underline the need for standardization and prospective controlled studies in GvHD prevention and treatment.

Disclosures:
No relevant conflicts of interest to declare.