Influence of bone marrow graft lymphocyte subsets on outcome after HLA-identical sibling transplants

Exp Hematol. 2001 Nov;29(11):1347-52. doi: 10.1016/s0301-472x(01)00737-8.

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.

Materials and 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.

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Antigens, CD34 / analysis
  • Bone Marrow Transplantation* / mortality
  • CD3 Complex / analysis
  • CD4-Positive T-Lymphocytes / transplantation
  • CD8-Positive T-Lymphocytes / transplantation
  • Child
  • Child, Preschool
  • Chronic Disease
  • Comorbidity
  • Cytomegalovirus Infections / epidemiology
  • Female
  • France / epidemiology
  • Graft Survival
  • Graft vs Host Disease / epidemiology
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / prevention & control
  • Hematologic Neoplasms / mortality
  • Hematologic Neoplasms / therapy
  • Histocompatibility
  • Humans
  • Incidence
  • Leukocyte Count
  • Lymphocyte Count
  • Lymphocyte Subsets / transplantation*
  • Male
  • Middle Aged
  • Neutrophils
  • Nuclear Family
  • Risk
  • Survival Analysis
  • Tissue Donors
  • Transplantation, Homologous

Substances

  • Antigens, CD34
  • CD3 Complex