Impact Of Infection And Drug Toxicity During Chemotherapy On The Incidence Of Graft-versus-host Disease And On Prognosis

Aim: About 60-70% AML patients have the indication of allogeneic hematopoietic stem cell transplantation(Allo-HSCT).Graft failure,impaired immune reconstitution,graft-versus-host disease and disease relapse are four major barrier to a successful allo-HSCT.GvHD,especially acute GvHD,is the most common factor among these four.Approximately 70% patients suffer from acute GvHD of different severity despite of prophylaxis.Corticosteroid is the first-line therapy for acute GvHD,but half of the patients fail to obtain long-term remission after standard steroid treatment and their prognosis is poor despite of all salvage treatment available.Thus,to improve acute GvHD prophylaxis to prevent the occurrence of acute GvHD is a critical way to improve the prognosis of allo-HSCT recipients.Overdosed immunosuppression,however,may result in delay of immune reconstitution and disease relapse.Our study aim to find a subgroup of patients with higher risk of acute GvHD and to establish a personalized acute GvHD prophylaxis in the future.Design: Infections and drug toxicities are two major complications during chemotherapy.They,to certain extent,active immune response locally or systemically.The pathophysiology of acute GvHD is known to be a cascade by the activation and proliferation of T lymphocytes and NK cells,the production of pro-inflammatory chemokines by these cells and the activation the more T lymphocytes.But whether former immune activation play a role in the occurrence of acute GvHD is not clear.Our study try to explore the impact of infection and drug toxicity during the chemotherapy prior to allo-HSCT on the incidence of acute GvHD and on prognosis of patients.Method: We retrospectively enrolled 345 patients transplanted from 21 French centers in the ALFA-0702 protocol and studied the relation between their incidence of infection and drug toxicity during the chemotherapy and their incidence of GvHD after the transplantation.Furthermore,we studied the impact of infection and drug toxicity on the prognosis of patients.Results: Immune stimulation by infection or drug toxicity during induction and/or consolidation increases the incidence of grade Ⅱ-Ⅳ acute GvHD(p=0.03),especially the incidence of stage 3-4 skin acute GvHD(p=0.001).Besides,cutaneous infection during induction increases the risk of chronic GvHD(p=0.04)and further has impact on relapse-free survival(p=0.048)and treatment-related mortality of patients(p=0.039).Conclusion: We identified a subgroup of patients with higher risk of acute GvHD and chronic GvHD.Whether they may benefit from stronger GvHD prophylaxis remains to be explored in a prospective study.