Therapy with OKT3 monoclonal antibody in refractory T cell acute lymphoblastic leukemia induces interleukin-2 responsiveness.
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.
Gramatzki
M
M
Department of Medicine III, University of Erlangen-Nürnberg, Germany.
Burger
R
R
Strobel
G
G
Trautmann
U
U
Bartram
C R
CR
Helm
G
G
Horneff
G
G
Alsalameh
S
S
Jonker
M
M
Gebhart
E
E
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001708:Biopterins / Q000031:analogs & derivatives / Q000032:analysis; D002869:Chromosome Aberrations; D003131:Combined Modality Therapy; D003165:Complement System Proteins / Q000032:analysis; D016207:Cytokines / Q000097:blood; D004351:Drug Resistance; D017809:Fatal Outcome; D006801:Humans; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000494:pharmacology* / Q000627:therapeutic use; D007621:Karyotyping; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000097:blood / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D008213:Lymphocyte Activation; D008297:Male; D008934:Mitogens / Q000494:pharmacology; D016853:Muromonab-CD3 / Q000627:therapeutic use*; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D019798:Neopterin; D016879:Salvage Therapy; D016176:T-Lymphocyte Subsets / Q000187:drug effects*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D016207:Cytokines; D007376:Interleukin-2; D008934:Mitogens; D016853:Muromonab-CD3; D001708:Biopterins; D019798:Neopterin; D003165:Complement System Proteins