Effect of Age and Previous Autologous Transplant on Treatment-Related Mortality and GVHD in 140 Patients Treated with Reduce-Intensity Conditioning and Allograft for Advanced Hematological Malignancies.
Authors: Corradini Paolo , Zallio Francesco , Mariotti Jacopo , Valagussa Pinuccia , Dodero Anna , Bregni Marco , Ciceri Fabio , Bacigalupo Andrea , Lucesole Moira , Patriarca Francesca , Rambaldi Andrea , Scimè Rosanna , Bandini Giuseppe , Gianni Alessandro M. , Tarella Corrado , Olivieri Attilio 
Published: October 2019

Abstract
Previous autografting and older age are traditionally considered poor prognostic factors for patients receiving myeloablative conditioning followed by allogeneic stem cell transplantation (SCT). Reduced intensity conditioning (RIC) achieved a significant reduction of treatment related mortality, but the influence of previously described risk factors on the outcome of this new strategy has not been fully described. We have evaluated if age older than 55 years and a failed autologous transplantation could have an impact on transplant-related mortality (TRM) and graft versus host disease (GVHD) occurrence. One hundred and forty allogeneic SCTs from HLA-identical sibling donors were analyzed: all patients received the same conditioning (Thiotepa 10mg/Kg, Fludarabine 60 mg/ms and Cyclophosphamide 60 mg/kg and) and GVHD prophylaxis (cyclosporin 2mg/kg and short course methotrexate). Patients were divided in two cohorts according to age: 86 patients were younger and 54 older than 55 years (range 20–69). Main pre-transplant characteristics were fairly well distributed in both cohorts, in terms of: sex, mismatch donor/recipient, CMV status, previous autografting, disease status at transplant, type of disease (lymphoid vs myeloid), stem cell source and number of previous lines of chemotherapy (<2 vs ≥2). Four-year treatment related mortality (TRM) was 13% for younger group and 17% for the older one (p=0.3), while overall survival (OS) was 58% and 59%, respectively (p=0.9). By univariate and multivariate analysis no pretransplant risk factor examined was found as significantly negative predictor of TRM; in particular no significantly association was found between a previously failed autograft and TRM in the younger (p=0.8) and in the older cohort (p=0.1). Instead, looking at GVHD, we observed that the occurrence of grade III–IV aGVHD was associated with a significantly worse TRM in both young (p=0.008) and elderly patients (p=0.005); similarly, extensive cGVHD was a predictor for worse TRM if compared to limited cGVHD in younger (p=0.8) and older patients (p=0.03). Finally, a strong association between favourable outcome and the onset of limited cGVHD was observed not only if compared to patients with extensive cGVHD but even compared to patients who never showed any sign of cGVHD; in fact 4-year OS curve for younger patients with limited cGVHD was 80% vs 50% of patients with no cGVHD (p=0.03); the same applies for the older cohort (4-years OS of 100% vs 48%, respectively). Our results indicate that: RIC can be safely applied to patients over 50 years; the deleterious effect of a previous failed autoBMT has been minimized by the RIC program. Moreover, severe GVHD still has a maior impact on the outcome; otherwise limited cGVHD seems an effective immunotherapy in high risk patients.