Ex vivo immunotherapy for patients with benzene-induced aplastic anemia

J Hematother Stem Cell Res. 2003 Oct;12(5):505-14. doi: 10.1089/152581603322448213.

Abstract

Aplastic anemia is a bone marrow failure disorder characterized by pancytopenia and a hypocellular marrow. Benzene is one of the etiologic agents capable of inducing the disease. With modest to severe aplastic anemia, one previously untreated patient and 13 patients who had failed immunosuppressive therapy were studied. Peripheral blood mononuclear cells from patients were expanded in vitro with a combination of cytokines and a calcium-mobilizing agents for 2 days, and the activated cells were infused intravenously once a week. In some cases, we used allogenic leukocytes instead of autologous cultured lymphocytes. After 6-35 weeks of the treatment, all patients had multilineage responses to this therapy and achieved complete disease remission, defined as normal blood count, independence from transfusion, and normal bone marrow histology. The therapy was safe and well tolerated with minimal side effects. The cultured cells produced interleukin-1 and induced immune responses in vivo. Serum interleukin-2 and interferon- gamma were detected following cell infusion. Finally, patients had sustained responses to the therapy and no relapse was found up to 18 months after cellular therapy.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Anemia, Aplastic / etiology
  • Anemia, Aplastic / therapy*
  • Benzene / poisoning
  • Blood Cell Count
  • Blood Transfusion
  • Bone Marrow / anatomy & histology
  • Bone Marrow / pathology
  • CD4-CD8 Ratio
  • Calcimycin / pharmacology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • Hemoglobins / analysis
  • Humans
  • Immunotherapy / methods*
  • Interferon-gamma / blood
  • Interleukin-1 / blood
  • Interleukin-2 / analysis
  • Interleukin-2 / pharmacology
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / transplantation
  • Male
  • Occupational Exposure / adverse effects
  • Recurrence
  • Remission Induction
  • Stem Cell Transplantation / adverse effects
  • Stem Cell Transplantation / methods*

Substances

  • Hemoglobins
  • Interleukin-1
  • Interleukin-2
  • Calcimycin
  • Interferon-gamma
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Benzene