Hairy cell leukemia, a B-cell neoplasm that is particularly sensitive to the cytotoxic effect of anti-Tac(Fv)-PE38 (LMB-2).

Anti-Tac(Fv)-PE38 (LMB-2) is a recombinant, single-chain immunotoxin composed of the variable domains of the anti-Tac (anti-CD25) monoclonal antibody fused to a truncated form of Pseudomonas exotoxin (PE). Until now, this agent has been reported to be very cytotoxic toward T-cell but not B-cell leukemic cells freshly obtained from patients and is being tested clinically in patients with CD25+ malignancies of both B- and T-cell origin. Hairy cell leukemia (HCL) is a B-cell malignancy in which the cells are usually CD25+ and their ex vivo sensitivity to LMB-2 was unknown. Malignant cells from the first HCL patient to be tested were very sensitive to the cytotoxic effect of LMB-2 in vitro (IC50, 1.1 ng/ml), and this patient responded clinically to LMB-2 administered systemically. Therefore, we decided to assess the potential clinical utility of LMB-2 in other patients with HCL. We tested fresh leukemic cells from nine additional CD25+ HCL patients. LMB-2 was very cytotoxic ex vivo in all patients with IC50s as low as 0.5 ng/ml. Malignant cells freshly obtained from patients with chronic lymphocytic leukemia were also sensitive to LMB-2 but not as sensitive as cells from HCL patients. These results indicate that CD25+ HCL is a B-cell neoplasm that is particularly sensitive to LMB-2, and this agent may be useful in patients who have failed standard therapies.