title: Reinfusion of autologous lymphocytes with granulocyte-macrophage colony-stimulating factor induces rapid recovery of CD4+ and CD8+ T cells after high-dose chemotherapy for metastatic breast cancer.
abstract: OBJECTIVE
  Repeated high-dose chemotherapy (HDCT) followed by peripheral-blood progenitor cell (PBPC) transplantation can induce a complete remission in patients with metastatic breast cancer sensitive to standard chemotherapy (CT), but the majority of patients relapse within 1 to 2 years. The immune system is seriously compromised after HDCT, which precludes the development of effective immunotherapy. We investigated whether autologous lymphocytes, reinfused after HDCT, could induce a rapid recovery of T cells.
  
  
  METHODS
  Three patients were monitored for immune recovery without reinfusion of lymphocytes. In the next 11 patients, stem cells were harvested after CT + granulocyte colony-stimulating factor (G-CSF) and lymphocytes were harvested after CT + granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-2. These patients received stem cells and G-CSF after the first HDCT; stem cells, G-CSF, and lymphocytes after the second; and stem cells, GM-CSF, and lymphocytes after the third HDCT.
  
  
  RESULTS
  Patients not receiving lymphocyte reinfusion had a very slow recovery of lymphocytes. In particular, CD4 counts remained low (< 200/microL for 9 months). Lymphocyte reinfusion had a significant effect on the recovery of lymphocytes, T cells, and CD8+ T cells (normalized on day 25). Recovery of CD4+ T cells was significantly accelerated by lymphocyte reinfusion and GM-CSF, leading to counts of 500/microL at 25 days.
  
  
  CONCLUSIONS
  Lymphocyte reinfusion with G-CSF had a significant effect on the recovery of CD8+ T cells, whereas rapid recovery of CD4+ T cells required lymphocyte reinfusion and GM-CSF, which possibly acts as a survival factor through activation of antigen presenting cells. Whether the rapid recovery of CD4+ and CD8+ T cells prevents or delays relapse of the disease should be further investigated.
authors.affiliation: Department of Medical Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands. p.favre@nki.nl
authors.forename: G C
authors.initials: GC
authors.lastname: de Gast
authors.forename: F A
authors.initials: FA
authors.lastname: Vyth-Dreese
authors.forename: W
authors.initials: W
authors.lastname: Nooijen
authors.forename: C J C
authors.initials: CJ
authors.lastname: van den Bogaard
authors.forename: J
authors.initials: J
authors.lastname: Sein
authors.forename: M M J
authors.initials: MM
authors.lastname: Holtkamp
authors.forename: G A M
authors.initials: GA
authors.lastname: Linthorst
authors.forename: J W
authors.initials: JW
authors.lastname: Baars
authors.forename: J H
authors.initials: JH
authors.lastname: Schornagel
authors.forename: S
authors.initials: S
authors.lastname: Rodenhuis
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D001804:Blood Transfusion, Autologous; D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D003131:Combined Modality Therapy; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D007376:Interleukin-2 / Q000627:therapeutic use; D017710:Lymphocyte Transfusion; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011994:Recombinant Proteins; D018709:Statistics, Nonparametric
chemical_list: D007376:Interleukin-2; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor