Synapse - Serious infection risk and immune recovery after double-unit cord blood transplantation without antithymocyte globulin

Serious infection risk and immune recovery after double-unit cord blood transplantation without antithymocyte globulin Journal Article

Authors:	Sauter, C.; Abboud, M.; Jia, X.; Heller, G.; Gonzales, A. M.; Lubin, M.; Hawke, R.; Perales, M. A.; Van Den Brink, M. R.; Giralt, S.; Papanicolaou, G.; Scaradavou, A.; Small, T. N.; Barker, J. N.
Article 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. © 2011 American Society for Blood and Marrow Transplantation.
Keywords:	adolescent; adult; child; controlled study; preschool child; school child; aged; child, preschool; middle aged; leukemia; retrospective studies; human cell; major clinical study; fludarabine; follow-up studies; infection; risk factors; aciclovir; cyclophosphamide; melphalan; herpes simplex; chronic myeloid leukemia; thiotepa; hodgkin disease; time factors; febrile neutropenia; acute leukemia; cord blood stem cell transplantation; myeloablative conditioning; myelodysplastic syndrome; nonmyeloablative conditioning; hematologic neoplasms; infant; graft versus host reaction; transplantation conditioning; enteritis; immunity; lymphatic leukemia; immunologic factors; vancomycin; cyclosporin a; graft vs host disease; mycophenolic acid 2 morpholinoethyl ester; bacterial infection; adenovirus infection; cytomegalovirus infection; mycosis; posaconazole; voriconazole; cytomegalovirus; clofarabine; micafungin; herpesvirus 4, human; opportunistic infection; epstein-barr virus infections; quinolone; aminoglycoside; epstein barr virus infection; anti-thymocyte globulin; unrelated donor umbilical cord blood transplantation; lung mycosis; cytomegalovirus infections; antilymphocyte serum; piperacillin; tazobactam
Journal Title:	Biology of Blood and Marrow Transplantation
Volume:	17
Issue:	10
ISSN:	1083-8791
Publisher:	Elsevier Inc.
Date Published:	2011-01-01
Start Page:	1460
End Page:	1471
Language:	English
DOI:	10.1016/j.bbmt.2011.02.001
PROVIDER:	scopus
PMCID:	PMC3165093
PUBMED:	21310254
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-80052970703&partnerID=40&md5=407926a365be3200c324091a4796f0c8
Notes:	--- - "Export Date: 3 October 2011" - "CODEN: BBMTF" - "Source: Scopus"