title: Influence of bone marrow graft lymphocyte subsets on outcome after HLA-identical sibling transplants.
abstract: OBJECTIVE
  The aim of this study was to analyze bone marrow lymphocyte subsets and CD34 cell dose and their influence on the outcomes of bone marrow transplantation.
  
  
  METHODS
  Forty-eight patients (median age 30 years, range 5-54) receiving HLA-identical sibling bone marrow transplantation for hematologic malignancies were analyzed.
  
  
  RESULTS
  Median number (range) of nucleated cells and CD34+ cells infused were 2.4 (0.4-6.0) x 10(8)/kg and 3.5 (0.5-13.0) x 10(6)/kg, respectively. Probability of neutrophil recovery was 97%. In a multivariate analysis, time to neutrophil recovery was shortened when a higher number of CD3/CD8 cells was infused (> or =1.0 x 10(7)/kg) (hazard ratio [HR] = 2.13, p = 0.018); when the patient was female or had negative cytomegalovirus serology (HR = 2.03, p = 0.03; HR = 0.41, p = 0.009; respectively). The incidence of grade II to IV acute graft-vs-host disease (GVHD) was 47%. Infusion of >1 x 10(7) CD4 infused/kg increased the risk of acute GVHD (HR = 2.86, p = 0.03). Nineteen of 40 patients at risk experienced chronic GVHD, the risk of which was increased by diagnosis of chronic leukemia (p = 0.03), <2.0 x 10(8) nucleated cells infused/kg (p = 0.05), and a low number of all lymphocyte subsets, except CD19. Estimated 3-year survival rate was 54%. Risk of death was increased in patients receiving <3.5 x 10(6)CD34 infused/kg (HR = 0.37, p = 0.02). Only six patients relapsed.
  
  
  CONCLUSIONS
  A high cell dose of CD3/CD8 is associated with faster neutrophil recovery, whereas a high cell dose of CD4+ cells increases the incidence of acute GVHD. A high number of nucleated cells and CD34+ cells infused was associated with decreased risk of chronic GVHD and improved survival, respectively.
authors.affiliation: Bone Marrow Transplant Unit, Saint Louis Hospital, 1, av. Claude Vellefaux, 75475 Paris, Cedex 10, France. vrocha@cbtg.com
authors.forename: V
authors.initials: V
authors.lastname: Rocha
authors.forename: M V
authors.initials: MV
authors.lastname: Carmagnat
authors.forename: S
authors.initials: S
authors.lastname: Chevret
authors.forename: O
authors.initials: O
authors.lastname: Flinois
authors.forename: H
authors.initials: H
authors.lastname: Bittencourt
authors.forename: H
authors.initials: H
authors.lastname: Esperou
authors.forename: F
authors.initials: F
authors.lastname: Garnier
authors.forename: P
authors.initials: P
authors.lastname: Ribaud
authors.forename: A
authors.initials: A
authors.lastname: Devergie
authors.forename: G
authors.initials: G
authors.lastname: Socié
authors.forename: L
authors.initials: L
authors.lastname: Dal'Cortivo
authors.forename: J P
authors.initials: JP
authors.lastname: Marolleau
authors.forename: D
authors.initials: D
authors.lastname: Charron
authors.forename: E
authors.initials: E
authors.lastname: Gluckman
authors.forename: C
authors.initials: C
authors.lastname: Rabian
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D018952:Antigens, CD34 / Q000032:analysis; D016026:Bone Marrow Transplantation / Q000401:mortality; D017252:CD3 Complex / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000637:transplantation; D018414:CD8-Positive T-Lymphocytes / Q000637:transplantation; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D015897:Comorbidity; D003586:Cytomegalovirus Infections / Q000453:epidemiology; D005260:Female; D005602:France / Q000453:epidemiology; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy; D006648:Histocompatibility; D006801:Humans; D015994:Incidence; D007958:Leukocyte Count; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000637:transplantation*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils; D009679:Nuclear Family; D012306:Risk; D016019:Survival Analysis; D014019:Tissue Donors; D014184:Transplantation, Homologous
chemical_list: D018952:Antigens, CD34; D017252:CD3 Complex