title: Long-term immune reconstitution and infection burden after mismatched hematopoietic stem cell transplantation.
abstract: Mismatched unrelated donor (MMUD) or umbilical cord blood (UCB) can be chosen as alternative donors for allogeneic stem cell transplantation but might be associated with long-lasting immune deficiency. Sixty-six patients who underwent a first transplantation from either UCB (n = 30) or 9/10 MMUD (n = 36) and who survived beyond 3 months were evaluated. Immune reconstitution was prospectively assessed at sequential time points after transplantation. NK, B, CD4(+), and CD8(+) T cells and their naïve and memory subsets, as well as regulatory T cells (Treg), were studied. Detailed analyses on infections occurring after 3 months were also assessed. The 18-month cumulative incidences of infection-related death were 8% and 3%, and of infections were 72% and 57% after MMUD and UCB transplantation, respectively. Rates of infection per 12 patient-month were roughly 2 overall (1 for bacterial, .9 for viral, and .3 for fungal infections). Memory, naïve CD4(+) and CD8(+)T cells, naïve B cells, and Treg cells reconstitution between the 2 sources were roughly similar. Absolute CD4(+)T cells hardly reached 500 per μL by 1 year after transplantation and most B cells were of naïve phenotype. Correlations between immune reconstitution and infection were then performed by multivariate analyses. Low CD4(+) and high CD8(+)T cells absolute counts at 3 months were linked to increased risks of overall and viral (but not bacterial) infections. When assessing for the naïve/memory phenotypes at 3 months among the CD4(+) T cell compartment, higher percentages of memory subsets were protective against late infections. Central memory CD4(+)T cells protected against overall and bacterial infections; late effector memory CD4(+)T cells protected against overall, bacterial, and viral infections. To the contrary, high percentage of effector- and late effector-memory subsets at 3 months among the CD8(+) T cell compartment predicted higher risks for viral infections. Patients who underwent transplantation from alternative donors represent a population with very high risk of infection. Detailed phenotypic analysis of immune reconstitution may help to evaluate infection risk and to adjust infection prophylaxis.
authors.affiliation: Service d'Hématologie Greffe, AP-HP Hôpital Saint Louis, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Servais
authors.affiliation: Service d'Hématologie Greffe, AP-HP Hôpital Saint Louis, Paris, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Lengline
authors.affiliation: AP-HP Hôpital Saint Louis, DBIM, Paris, France.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Porcher
authors.affiliation: Immunologie, AP-HP Hôpital Saint Louis, Paris, France.
authors.forename: Maryvonnick
authors.initials: M
authors.lastname: Carmagnat
authors.affiliation: Service d'Hématologie Greffe, AP-HP Hôpital Saint Louis, Paris, France.
authors.forename: Régis
authors.initials: R
authors.lastname: Peffault de Latour
authors.affiliation: Service d'Hématologie Greffe, AP-HP Hôpital Saint Louis, Paris, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Robin
authors.affiliation: Service d'Hématologie Greffe, AP-HP Hôpital Saint Louis, Paris, France.
authors.forename: Flore
authors.initials: F
authors.lastname: Sicre de Fontebrune
authors.affiliation: Immunologie, AP-HP Hôpital Saint Louis, Paris, France; Inserm U 940, Hôpital Saint Louis, Paris, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Clave
authors.affiliation: Immunologie, AP-HP Hôpital Saint Louis, Paris, France.
authors.forename: Guitta
authors.initials: G
authors.lastname: Maki
authors.affiliation: Immunologie, AP-HP Hôpital Saint Louis, Paris, France.
authors.forename: Clémence
authors.initials: C
authors.lastname: Granier
authors.affiliation: Service d'Hématologie Greffe, AP-HP Hôpital Saint Louis, Paris, France.
authors.forename: Alienor
authors.initials: A
authors.lastname: Xhaard
authors.affiliation: Service d'Hématologie Greffe, AP-HP Hôpital Saint Louis, Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Dhedin
authors.affiliation: Service des Maladies Infectieuses et Tropicales, AP-HP Hôpital Saint Louis, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Molina
authors.affiliation: Immunologie, AP-HP Hôpital Saint Louis, Paris, France; Inserm U 940, Hôpital Saint Louis, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Toubert
authors.affiliation: Immunologie, AP-HP Hôpital Saint Louis, Paris, France; Inserm U 940, Hôpital Saint Louis, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Moins-Teisserenc
authors.affiliation: Service d'Hématologie Greffe, AP-HP Hôpital Saint Louis, Paris, France; Inserm U 940, Hôpital Saint Louis, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, France. Electronic address: gerard.socie@sls.aphp.fr.
authors.forename: Gérard
authors.initials: G
authors.lastname: Socie
mesh_terms: D000293:Adolescent; D000328:Adult; D001424:Bacterial Infections / Q000209:etiology / Q000276:immunology / Q000473:pathology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D002648:Child; D006085:Graft Survival; D006680:HLA Antigens / Q000276:immunology; D019337:Hematologic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D006650:Histocompatibility Testing; D006801:Humans; D007156:Immunologic Memory; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology; D018655:Lymphocyte Count; D008875:Middle Aged; D009181:Mycoses / Q000209:etiology / Q000276:immunology / Q000473:pathology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D014019:Tissue Donors; D023001:Transplantation Tolerance; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014777:Virus Diseases / Q000209:etiology / Q000276:immunology / Q000473:pathology*
chemical_list: D006680:HLA Antigens
keywords: Hematopoietic stem cell transplantation; Immune reconstitution; Infection