Influence of the Intensity of the Conditioning Regimen on the Characteristics of Acute and Chronic Graft Versus Host Disease after Allogeneic Transplantation.
Authors: Diez-Campelo Maria , Perez-Simon Jose A. , Martino Rodrigo , Valcarce Daniel , Urbano Alvaro , Caballero Dolores M. , Leon Angel , Brunet Salut , Carreras Enric , Cañizo Consuelo Maria , Sierra Jorge , San Miguel Jesus F. 
Published: October 2019

Abstract
Although increasing numbers of allogeneic stem cell transplants are being performed worldwide using reduced intensity conditionings (allo-RIC), most of the current experience and knowledge on the characteristics of graft-versus-host disease (GVHD), especially chronic GVHD (cGVHD), comes from the use of myeloablative conditioning regimens (MCR). We have analyzed the incidence and characteristics of GVHD among 150 consecutive patients undergoing allo-RIC as compared to 88 concomitant patients undergoing MCR. All patients analized received peripheral blood stem cells (PBSC) from an HLA identical sibling and the same GVHD prophylaxis (cyclosporine and methotrexate). Incidences of acute GVHD (aGVHD) were 69% and 47% among MCR and allo-RIC, respectively (p<0.001). Incidences of grades 2–4 aGVHD were 51% vs 33%, respectively (p=0.0009). Regarding organ involvement, no signifficant differences were observed between either subgroups. Skin was the organ most frecuently involved in both subgroups (83 % vs 75.3% cases among MCR and allo-RIC patients, respectively; p=0.08). Regarding response to treatment, no significant differences were observed between both subgroups, with 66.1% vs 52.2% of patients reaching complete remission (CR) after first line therapy. Interestingly, gastrointestinal tract was the organ most frequently involved in treatment failure in both subgroups: 16 (66.6%) and 20 (80%) of MCR and allo-RIC patients (p=0.21) had gut GVHD relapse/progression/no response with or without other organs involvement. Liver was involved in treatment failure in 6 (25%) vs 12 (48%) patients undergoing MCR vs allo-RIC, respectively (p=0.02). In multivariate analysis, only type of conditioning (MCR vs RIC) significantly influenced the incidence of overall aGVHD: HR= 2.16 (95 % CI: 1.52–3.07), p<0.0001. Incidences of chronic GVHD (cGVHD) were 68% and 76% among MCR and allo-RIC patients, respectively (p=0.03), although patients who developed cGVHD, incidence of extensive cGVHD was higher in the MCR group as compared to allo-RIC (88 vs 64%, p=0.01). A higher incidence of severe skin cGVHD involvement was observed among MCR recipients (39.4% vs 9.6%, respectively; p=0.008). As far as response to immunosupressive treatment 41.4% of MCR vs 58.2% of allo-RIC patients reached CR (p=0.43). Among patients who reached CR of cGVHD, a high incidence of cGVHD relapse was observed in both subgroups (58.3% vs 50% among MCR vs allo-RIC patients), with most relapses occurring in the first year after inmunosuppression was stopped. Among patients who developed extensive cGVHD, 83.3% vs 37.9% of patients undergoing MCR vs allo-RIC required systemic immmunosupression 3 years after allogeneic PBSC transplantation (p=0.009). Thus, overall, duration of immunosupression was shorter among allo-RIC patients, since 36 months after transplant 68.8% vs 35.5% of patients receiving MCR vs RIC required systemic immunosupression (p=0.028). In conclusion, the use of reduced intensity conditioning regimens decreases the incidence of both acute and extensive cGVHD after PBSC allogeneic transplantation, thus reducing the immunosupression requirements at the long term follow up.