title: Serious infection risk and immune recovery after double-unit cord blood transplantation without antithymocyte globulin.
abstract: Factors contributing to infection risk after cord blood transplantation (CBT) include the use of anti-thymocyte globulin (ATG), prolonged neutropenia, and failure to transfer immunity. In the present study, we investigated the potential of double-unit CBT without ATG to reduce the risk of infection and evaluated the nature of serious infections in the first year after CBT using this approach. Seventy-two predominantly adult patients underwent CBT for hematologic malignancies; of these, 52 patients received myeloablative conditioning, and 20 received nonmyeloablative conditioning. The peak incidences of bacterial infections (32%), fungal infections (14%), and bacterial/fungal pneumonias (10%) occurred in the first 30 days posttransplantation. Three such infections contributed to early mortality. The peak incidence of viral infections was 31-60 days posttransplantation, affecting 30% of patients. Cytomegalovirus (CMV) was the most common viral infection. CMV infections occurring before day 120 (n = 23) had no relationship with graft-versus-host disease (GVHD), whereas CMV infections occurring after day 120 (n = 5), along with all cases of Epstein-Barr virus viremia (n = 5) and adenoviral enteritis (n = 2), occurred exclusively in the context of GVHD therapy or corticosteroid use for another indication. Viral infections had the highest lethality: 2 were a direct cause of death, and 3 contributed to death. Patients exhibited steady immune recovery, achieving a median CD3(+)4(+) T cell count >200 cells/μL by day 120 post-CBT, and no infection-related deaths occurred after day 120. Our results suggest that double-unit CBT without ATG is associated with prompt T cell recovery, and, unlike in CBT incorporating ATG, infection is rarely a primary cause of death. However, CBT without ATG is associated with a significant risk of GVHD, and serious infections remain a challenge, especially in the setting of GVHD. New strategies are needed to further reduce infectious complications after CBT; these will require earlier neutrophil recovery and more effective prevention of GVHD, ideally without the profound T cell depletion associated with ATG therapy.
authors.affiliation: Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
authors.forename: Craig
authors.initials: C
authors.lastname: Sauter
authors.forename: Michelle
authors.initials: M
authors.lastname: Abboud
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Jia
authors.forename: Glenn
authors.initials: G
authors.lastname: Heller
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Gonzales
authors.forename: Marissa
authors.initials: M
authors.lastname: Lubin
authors.forename: Rebecca
authors.initials: R
authors.lastname: Hawke
authors.forename: Miguel-Angel
authors.initials: MA
authors.lastname: Perales
authors.forename: Marcel R
authors.initials: MR
authors.lastname: van den Brink
authors.forename: Sergio
authors.initials: S
authors.lastname: Giralt
authors.forename: Genovefa
authors.initials: G
authors.lastname: Papanicolaou
authors.forename: Andromachi
authors.initials: A
authors.lastname: Scaradavou
authors.forename: Trudy N
authors.initials: TN
authors.lastname: Small
authors.forename: Juliet N
authors.initials: JN
authors.lastname: Barker
mesh_terms: D000328:Adult; D000368:Aged; D000961:Antilymphocyte Serum / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D036101:Cord Blood Stem Cell Transplantation; D003587:Cytomegalovirus; D003586:Cytomegalovirus Infections / Q000401:mortality* / Q000517:prevention & control; D020031:Epstein-Barr Virus Infections / Q000401:mortality* / Q000517:prevention & control; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000401:mortality / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy; D004854:Herpesvirus 4, Human; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage*; D007223:Infant; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D019172:Transplantation Conditioning
chemical_list: D000961:Antilymphocyte Serum; D007155:Immunologic Factors