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Effects of therapy with T101 ricin A-chain immunotoxin in two leukemia
patients
G Laurent, J Pris, JP Farcet, P Carayon, H Blythman, P Casellas, P Poncelet and FK Jansen
Two leukemia patients, refractory to chemotherapy, were treated with
T101-ricin A-chain immunotoxin (T101 IT). Patient 1 (T-ALL) received a
single 13.5 mg dose of T101 IT IV (12-hour infusion). Patient 2 (B-CLL) was
treated with a daily 25 mg dose of T101 IT IV (two-hour infusion) over
three consecutive days. Patient 2 also received 300 mg of chloroquine IM on
days two and three as enhancer. In vivo binding of T101 IT was demonstrated
by FACS analysis using either an antimouse Ig- FITC or anti-A-chain-FITC
antibodies. Following IT therapy, the expression of T65 antigen on target
cells dropped to 50% and 20% of pretreatment levels, respectively. In
patient 1, circulating blast cells remained unsaturated during therapy
while in patient 2, cells were fully saturated for four to six hours
following each infusion. Pharmacokinetic studies showed a rapid clearance
of T101 IT after IV administration. Antimouse and anti-A-chain antibodies
could not be detected. There were no treatment-related adverse effects. In
patient 1 a rapid but transient decrease of target cells was observed,
possibly related to the administration of the antibody part of T101 IT. In
contrast, patient 2 showed a 40% reduction of the lymphocyte count, which
remained stable over a period of 2 weeks. Such a clinical benefit following
IT therapy in patient 2 could be ascribed to the absence of circulating
free antigen and the complete saturation of target cells.
Volume 67,
Issue 6,
pp. 1680-1687,
06/01/1986
Copyright © 1986 by The American Society of Hematology
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