Viral Infections after Umbilical Cord Blood Transplant: A Retrospective Analisys of 156 Children Transplanted at a Single Institution

Umbilical cord blood (UCB) is an alternative option for hematopoietic stem cell transplantation and it has been successfully used to treat children with malignant and non malignant diseases. The slower rate of neutrophil engraftment and delayed immune reconstitution impose a substantial risk for infections and mortality.  Furthermore, the use of anti-thymocyte globulin (ATG) has been linked to a higher risk of viral infections. In order to assess the occurrence of viral infections we retrospectively analyzed the outcomes of 156 children who underwent a UCB transplant (UCBT) between January 1996 and October 2012 in a single institution. Diagnostic methods varied over time: initially antigenemia, immunofluorescence and immunoenzymatic tests were used and since 2005 Polymerase Chain Reaction (PCR) was employed for vigilance and diagnosis of viral reactivation. Fifty and one girls and 105 boys with a median age of 60 months (range 2 – 168 months) were transplanted for malignant (48 pts) and non-malignant diseases: BM failure syndromes: 55 patients (pts), primary immunodeficiencies (PID): 41 pts and inborn errors of metabolism (IEM): 12 pts. HLA compatibility: 6/6 or 5/6: 98 pts and 4/6: 58 pts. Conditioning Regimen was based on chemotherapy in 119 pts and TBI based in 37 pts. The median number of Total Nucleated Cell was 5,2 x 10⁷/Kg (range: 1,4 - 36,4 x 10⁷/Kg). A hundred and forty three pts were evaluable for engraftment with a median time for neutrophil recovery of 26 days and for platelet recovery of 42 days. Viral infection occurred in 99/156 pts. In the univariate analysis it was more frequent in pts who received ATG: 87/122 (p 0,0001), in those who developed acute GVHD: 65/80 (p 0,0001) or chronic GVHD: 49/59 (p 0,0001) and in 4/6 HLA mismatched UCBT (p 0,001). The most frequent virus detected in this cohort was Cytomegalovirus (CMV): 74 pts, followed by Epstein-Barr virus (EBV): 14 pts and adenovirus: 8pts. CMV status pre-transplant correlated with higher incidence of CMV infection post transplant. Moreover, viral infections were associated with bacterial infection in 79/127 pts (p 0,01). Death occurred in 81 pts and the main cause was bacterial infection. In this analysis the presence of viral infection per se was not associated to a high mortality. Conclusion: we observed a high prevalence of viral infections among UCB recipients and a positive association of its occurrence with HLA-mismatch, development of acute or chronic GVHD and the use of ATG. Viral infections were usually associated with other infectious agents such bacteria or fungi and this could be an important factor for morbidity and mortality. Currently, close PCR surveillance allows early detection of viremia and aggressive treatment.