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1996-02-27
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Document 0576
DOCN M9630576
TI Radioimmunotherapy of interleukin-2R alpha-expressing adult T-cell
leukemia with Yttrium-90-labeled anti-Tac.
DT 9603
AU Waldmann TA; White JD; Carrasquillo JA; Reynolds JC; Paik CH; Gansow OA;
Brechbiel MW; Jaffe ES; Fleisher TA; Goldman CK; et al; Metabolism
Branch, National Cancer Institute, National Institutes; of Health,
Bethesda, MD 20892, USA.
SO Blood. 1995 Dec 1;86(11):4063-75. Unique Identifier : AIDSLINE
MED/96082159
AB Adult T-cell leukemia (ATL) is a malignancy of mature lymphocytes caused
by the retrovirus human T-cell lymphotropic virus-I. It is an aggressive
leukemia with a median survival time of 9 months; no chemotherapy
regimen appears successful in inducing long-term disease-free survival.
The scientific basis of the present study is that ATL cells express
high-affinity interleukin-2 receptors identified by the anti-Tac
monoclonal antibody, whereas normal resting cells do not. To exploit
this difference, we administered anti-Tac armed with Yttrium-90 (90Y) to
18 patients with ATL initially (first 9 patients) in a phase I
dose-escalation trial and subsequently (second group of 9 patients) in a
phase II trial involving a uniform 10-mCi dose of 90Y-labeled anti-Tac.
Patients undergoing a remission were permitted to receive up to eight
additional doses. At the 5- to 15-mCi doses used, 9 of 16 evaluable
patients responded to 90Y anti-Tac with a partial (7 patients) or
complete (2 patients) remission. The responses observed represent
improved efficacy in terms of length of remission when compared with
previous results with unmodified anti-Tac. Clinically meaningful (> or =
grade 3) toxicity was largely limited to the hematopoietic system. In
conclusion, radioimmunotherapy with 90Y anti-Tac directed toward the
IL-2R expressed on ATL cells may provide a useful approach for treatment
of this aggressive malignancy.
DE Adult Animal Antibodies, Anti-Idiotypic/BIOSYNTHESIS Antibodies,
Monoclonal/ADMINISTRATION & DOSAGE/ADVERSE EFFECTS/ THERAPEUTIC USE
Female Human Immunocompetence Leukemia-Lymphoma, T-Cell, Acute,
HTLV-I-Associated/IMMUNOLOGY/ METABOLISM/*RADIOTHERAPY Lymphocyte
Count Male Mice Middle Age *Radioimmunotherapy Receptors,
Interleukin-2/IMMUNOLOGY/METABOLISM T-Lymphocytes Yttrium
Radioisotopes/ADMINISTRATION & DOSAGE/ADVERSE EFFECTS/ *THERAPEUTIC USE
CLINICAL TRIAL CLINICAL TRIAL, PHASE I CLINICAL TRIAL, PHASE II
JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).