BACKGROUND: Reduced intensity stem cell cell transplantation (RIST) from unrelated umbilical cord blood (RI-UCBT) is a novel therapeutic strategy for patients with malignant and non-malignant diseases, but infectious complications of this procedure have not been previously well described. OBJECTIVE: To analyze the incidence and characteristics of documented infections in patients with hematologic malignancies undergoing RI-UCBT. PATIENTS AND METHODS: We retrospectively investigated the incidence and characteristics of infection in a series of 46 patients with hematologic malignancies or severe aplastic anemia who underwent RI-UCBT from March 2002 to August 2003. The median age was 57 years (range 20-70). Acyclovir, co-trimoxazole, fluconazole, and tosufloxacin were administered for anti-infectious prophylaxis. GVHD prophylaxis was cyclosporine alone. RESULTS: Severe neutropenia developed in all patients, lasting for a median of 17 days. 43 patients (93%) achieved full chimerism by day 56. 15 patients (33%) developed grade II-IV acute graft-versus-host disease and received additional steroid therapy. Bacterial infections occurred in 13 patients (28%). The causative organisms were gram-positive (n=10) and gram-negative organisms (n=3). Fungal infections were documented in five patients (11%). 17 of 46 cytomegalovirus (CMV) - seropositive patients (37%) developed CMV antigenemia at a median of 43 days, but no CMV disease developed. All viremic patients responded to intravenous foscarnet therapy. 18 patients (39%) died before day 100 after transplantation. Infection was considered the primary cause of death in five patients (disseminated aspergillosis=2, MRSA sepsis=1, P. aeruginosa sepsis=1, and E. faecium sepsis=1) and contributed to death in another six. Multivariate analysis showed that steroid therapy was an independent risk factor for subsequent documented CMV antigenemia. DISCUSSION: This study demonstorates that bacterial and fungal infection is a major complication in adults undergoing RI-UCBT. Longer period of neutropenia, acute GVHD, immunosuppressive therapy, and impaired immune response may also contribute to the infections seen in RI-UCBT patients. Low incidence and lack of mortality due to CMV disease were observed. Thorough studies of the risk of post-transplant infection are necessary to optimize surveillance as well as pre-emptive and/or prophylactic treatment strategies in the RI-UCBT setting.
Full conference title:
American Society of Hematology 45th Annual Meeting
- ASH 45th (2003)