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Blood, Vol. 94 No. 10 (November 15), 1999:
pp. 3340-3348
Responses in Refractory Hairy Cell Leukemia to a Recombinant
Immunotoxin
Robert J. Kreitman,
Wyndham H. Wilson,
David Robbins,
Inger Margulies,
Maryalice Stetler-Stevenson,
Thomas A. Waldmann, and
Ira Pastan
From the Laboratory of Molecular Biology, the Laboratory of Clinical
Pathology, the Metabolism Branch, and the Medicine Branch, National
Cancer Institute, National Institutes of Health, Bethesda, MD.
We report major responses in 4 of 4 patients with hairy cell
leukemia (HCL) who have recently been treated on a phase I trial with
the recombinant immunotoxin LMB-2. The immunotoxin, designed to target
CD25+ malignancies, is composed of the Fv portion of the
anti-Tac (anti-CD25) antibody, fused to a 38-kD truncated form of
Pseudomonas exotoxin A, and has previously been called
anti-Tac(Fv)-PE38. All 4 HCL patients were resistant to standard and
salvage therapies for HCL, including 2-chlorodeoxyadenosine (CdA) and
interferon  , and all patients responded to LMB-2 after a single
cycle. One patient treated with 2 cycles had a complete remission (CR),
with regression of HCL cells from the blood and marrow and resolution of splenomegaly and pancytopenia. As is typical for patients in CR
after treatment with CdA, minimal residual disease was detectable by
flow cytometry of the bone marrow aspirate. This patient has not
relapsed after 11 months. Three other patients had 98% to 99.8%
reductions in malignant circulating cells. These results represent a
proof of principal that targeted therapy with recombinant Fv-containing
proteins can be clinically useful. LMB-2 may be an effective new
therapy for patients with chemotherapy-resistant CD25+ HCL.
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