Feasibility of Cyclosporine Prophylaxis Withdrawal in Critically Ill Allogenic Hematopoietic Stem Cell Transplant Patients Admitted to the Intensive Care Unit With No GVHD

Abstract

Twenty percent of allogenic hematopoietic stem cell transplantation (allo-HSCT) patients require intensive care unit (ICU) admission. Feasibility and long-term consequences of cyclosporine graft-versus-host disease (GVHD) prophylaxis withdrawal in the ICU are unknown. To assess the impact of cyclosporine prophylaxis withdrawal in critically ill allo-HSCT patients admitted to the ICU on GVHD incidence and to evaluate 6-month overall survival according to cyclosporine withdrawal and GVHD occurrence. From 2010 to 2020, 101 critically ill allo-HSCT patients admitted to the ICU in our institution were included. All received cyclosporine as GVHD prophylaxis. None of them had GVHD at ICU admission. Patients were admitted in the ICU after a median time of 11 days (5.5-18) after allo-HSCT. ICU, hospital mortality, and 6-month mortality were 43.6%, 56.4%, and 59.4%, respectively. Cyclosporine was withdrawn for 52 and continued for 49 patients in the ICU. A total of 38.6% (n=39) developed secondarily acute GVHD (aGVHD) after a median of 28 days (15-40) after cyclosporine was discontinued. In 74.4% (n=29) of cases, patients in the hematology ward developed aGVHD after ICU discharge. Cyclosporine dosages were similar in both groups. Factors independently associated with aGVHD occurrence in multivariate analysis were cyclosporine withdrawal in the ICU (subdistribution hazard ratios [sHR]=2.04, 95% confidence interval [CI]=1.02-4.1, P=.044), renal replacement therapy (RRT) (sHR=0.43, 95% CI=0.19-0.9, P=.03) and fungal prophylaxis (sHR=2.62, 95% CI=1.35-5.07, P=.004). Cyclosporine withdrawal in the ICU was associated with poorer 6-month overall survival (OS) (HR=1.96, 95% CI=1.16-3.33, P=.012), but after adjusting on severity (simplified acute physiology score, vasopressors, mechanical ventilation and RRT requirement), 6-month OS did not differ (HR=1.35, 95% CI=0.76-2.42, P=.30). GVHD occurrence after ICU stay was significantly associated with better 6-month OS in unadjusted (HR=0.53, 95% CI=0.31-0.90, P=.02) and severity-adjusted analysis (HR=0.54, 95% CI=0.31-0.93, P=.028). Cyclosporine prophylaxis withdrawal in critically ill allo-HSCT patients in the ICU appears to be feasible and did not impair long-term outcome.