Therapy with OKT3 monoclonal antibody in refractory T cell acute lymphoblastic leukemia induces interleukin-2 responsiveness

Leukemia. 1995 Mar;9(3):382-90.

Abstract

Administration of cytokines to patients with leukemia or lymphoma may recruit dormant malignant cells into cell cycle and thus make them more susceptible to chemotherapy. We treated a patient with refractory T cell acute lymphoblastic leukemia (ALL) with OKT3 monoclonal antibody and observed a dramatic but transient decrease of lymphoblasts. The T ALL cells were rather mature by morphology and immunophenotyping, expressing CD7, CD4, CD8 and CD3 surface antigens and nuclear TdT. Cytogenetic analysis revealed inversion of chromosome 14(q11q32.1). A total of 500 mg OKT3 (maximum dose 50 mg/day) was given. A decrease of lymphoblasts in the blood and a reduction of spleen size was observed. Complement levels dropped remarkably. Despite increasing serum levels of tumor necrosis factor, treatment was well tolerated overall. CD3 therapy induced strong IL-2 responsiveness of the lymphoblasts. Thus, OKT3 antibody treatment not only significantly decreased CD3-positive tumor cells, but also induced IL-2-mediated proliferation. This may also allow sequential application of CD3 and IL-2 to render certain T cell tumors more susceptible to chemotherapy.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biopterins / analogs & derivatives
  • Biopterins / analysis
  • Chromosome Aberrations
  • Combined Modality Therapy
  • Complement System Proteins / analysis
  • Cytokines / blood
  • Drug Resistance
  • Fatal Outcome
  • Humans
  • Immunophenotyping
  • Interleukin-2 / pharmacology*
  • Interleukin-2 / therapeutic use
  • Karyotyping
  • Leukemia-Lymphoma, Adult T-Cell / blood
  • Leukemia-Lymphoma, Adult T-Cell / genetics
  • Leukemia-Lymphoma, Adult T-Cell / pathology
  • Leukemia-Lymphoma, Adult T-Cell / therapy*
  • Lymphocyte Activation
  • Male
  • Mitogens / pharmacology
  • Muromonab-CD3 / therapeutic use*
  • Neoplastic Stem Cells / drug effects*
  • Neopterin
  • Salvage Therapy
  • T-Lymphocyte Subsets / drug effects*
  • Tumor Cells, Cultured / drug effects

Substances

  • Cytokines
  • Interleukin-2
  • Mitogens
  • Muromonab-CD3
  • Biopterins
  • Neopterin
  • Complement System Proteins