Effect of Lym-1 radioimmunoconjugate on refractory chronic lymphocytic leukemia.
BACKGROUND
Although chronic lymphocytic leukemia is usually indolent and responsive to treatment early in its course, later stages are characterized by inexorable progression despite standard treatment so that new therapies are needed. Because malignant lymphocytes have characteristic surface antigens, the role of monoclonal antibodies is worthy of intensive investigation.


METHODS
Five patients with refractory chronic lymphocytic leukemia were treated with a novel radioimmunoconjugate, 131I-Lym-1, reactive with antigenic sites on malignant B lymphocytes. 131I-Lym-1 was given to the patients in doses of 20-65 mCi at 2-6-week intervals.


RESULTS
Radioimmunoconjugate treatment using 131I-Lym-1 induced objective responses with dramatic reduction in lymphadenopathy and, in two patients, normalization of leukocyte counts. However, lymphocytes continued to be the dominate cells in the peripheral blood and bone marrow. Because these patients had advanced disease associated with preexisting peripheral cytopenias, requiring repeated transfusions, and recurrent infections, hematopoietic toxicity from 131I-Lym-1 was difficult to evaluate. The patients seemed to tolerate at least 200 mCi of 131I given at these dose levels, and intervals before toxicity added to their existing peripheral cytopenias. Radionuclide doses in excess of 300 mCi aggravated preexisting thrombocytopenia.


CONCLUSIONS
Although the data raise the possibility of a role for 131I-Lym-1 monoclonal antibody in the treatment of chronic lymphocytic leukemia, strategies to address the radionuclide-induced thrombocytopenia are essential before this intervention can become a clinically useful therapeutic modality for chronic lymphocytic leukemia.
DeNardo
G L
GL
Division of Hematology and Oncology, School of Medicine, University of California, Davis.
Lewis
J P
JP
DeNardo
S J
SJ
O'Grady
L F
LF
D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D000951:Antigens, Neoplasm / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D005260:Female; D006801:Humans; D007145:Immunoglobulin kappa-Chains / Q000276:immunology; D000922:Immunotoxins / Q000008:administration & dosage*; D007457:Iodine Radioisotopes / Q000008:administration & dosage; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology / Q000532:radiotherapy*; D008297:Male; D051379:Mice; D008875:Middle Aged; D010865:Pilot Projects; D016499:Radioimmunotherapy / Q000379:methods*; D014916:Whole-Body Irradiation
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D007145:Immunoglobulin kappa-Chains; D000922:Immunotoxins; D007457:Iodine Radioisotopes