Incidence and outcome of infections after unrelated cord blood transplantation in patients with hematological malignancies: a long-term single center experience

Introduction: Unrelated cord blood (UCB) has become an alternative stem cell source for patients with hematological malignancies requiring allogeneic transplantation and lacking a HLA-matched donor. Infections after an UCB transplantation (UCBT) represent a leading cause of morbidity and mortality. The aim of this study was to evaluate the incidence, risk factors and outcome of infections occurring after an UCBT. Materials (or patients) and methods: We performed a retrospective study in 75 patients who received a UCBT at our center between July 1995 and July 2013: there were 51 children (median age 9 years, range 1-17) and 24 adults (median age 28 years, range 18-60). Patients were affected by high risk hematological malignancies: 22 had acute myeloid leukemia, 47 acute lymphoblastic leukemia and 6 chronic myeloid leukemia. All patients received a myeloablative conditioning regimen, in vivo T-cell depletion with antilymphocyte serum, and cyclosporine plus corticosteroid as GVHD prophylaxis. Fluconazole, acyclovir and ciprofloxacin were administered as prophylaxis for fungal, viral and bacterial infections, respectively. All patients underwent CMV antigenemia or DNAemia monitoring, while EBV DNAemia monitoring was performed since 2002 for the last 40 patients. Results: The incidences of bacteremia, proven/probable invasive fungal diseases (IFD), CMV infection, EBV infection and herpes zoster disease were 88%, 21%, 61%, 20% and 17% of transplants, respectively. Out of 80 bacterial isolates, 44% were Gram negative and 56% Gram positive. IFDs were caused by filamentous fungi in 62% of cases. Gastrointestinal CMV disease was documented in 4% of patients with virus infection. Out of 8 patients with EBV infection, 3 developed a posttransplant lymphoproliferative disorder (PTLD) (fatal in 2 cases). The distribution of the infections in the early (days 1- 40 from transplant), late (days 41- 100), very late (days 101 - 365) phases and after day 365 are detailed in Figure 1. Bacterial, fungal and CMV infections were documented mainly during the early engraftment phase, while EBV and herpes zoster infections were generally documented after day 100. The duration of pre-engraftment neutropenia did not correlate significantly with an increased infectious risk. Grade II-IV acute GVHD was significantly predictive of the development of an IFD (HR 0.28; IC: 0.09 – 0.87; P¼0.029). At a median follow-up of 10 years, 30 of 75 (40%) patients are still alive. Infections represented the primary cause of death in 24% of patients. The attributable mortality rate for bacterial and fungal infections accounted for 4.5% and 31%, respectively. Conclusion: Our study confirms the high rate of infectious complications occurring after an UCBT. In agreement with other experiences, the early engraftment phase represented the period at higher risk of bacterial, fungal and CMV infections. After this time period, a moderate risk of developing IFDs persists up to 6 months, especially in patients with GVHD. Infections by viruses other than CMV have been more frequently documented after the very late phase posttransplant. These epidemiological findings should be considered for the definition of tailored anti-fungal prophylaxis and virological pre-emptive strategies. Disclosure of Interest: None declared.