BACKGROUND: Hairy-cell leukemia that is resistant to treatment with purine analogues, including cladribine, has a poor prognosis. We tested the safety and efficacy of an immunotoxin directed against a surface antigen that is strongly expressed by leukemic hairy cells. METHODS: RFB4(dsFv)-PE38 (BL22), a recombinant immunotoxin containing an anti-CD22 variable domain (Fv) fused to truncated pseudomonas exotoxin, was administered in a dose-escalation trial by intravenous infusion every other day for a total of three doses. RESULTS: Of 16 patients who were resistant to cladribine, 11 had a complete remission and 2 had a partial remission with BL22. The three patients who did not have a response received low doses of BL22 or had preexisting toxin-neutralizing antibodies. Of the 11 patients in complete remission, 2 had minimal residual disease in the bone marrow or blood. During a median follow-up of 16 months (range, 10 to 23), 3 of the 11 patients who had a complete response relapsed and were retreated; all of these patients had a second complete remission. In 2 of the 16 patients, a serious but completely reversible hemolytic-uremic syndrome developed during the second cycle of treatment with BL22. Common toxic effects included transient hypoalbuminemia and elevated aminotransferase levels. CONCLUSIONS: BL22 can induce complete remissions in patients with hairy-cell leukemia that is resistant to treatment with purine analogues.
BACKGROUND:Hairy-cell leukemia that is resistant to treatment with purine analogues, including cladribine, has a poor prognosis. We tested the safety and efficacy of an immunotoxin directed against a surface antigen that is strongly expressed by leukemic hairy cells. METHODS: RFB4(dsFv)-PE38 (BL22), a recombinant immunotoxin containing an anti-CD22 variable domain (Fv) fused to truncated pseudomonas exotoxin, was administered in a dose-escalation trial by intravenous infusion every other day for a total of three doses. RESULTS: Of 16 patients who were resistant to cladribine, 11 had a complete remission and 2 had a partial remission with BL22. The three patients who did not have a response received low doses of BL22 or had preexisting toxin-neutralizing antibodies. Of the 11 patients in complete remission, 2 had minimal residual disease in the bone marrow or blood. During a median follow-up of 16 months (range, 10 to 23), 3 of the 11 patients who had a complete response relapsed and were retreated; all of these patients had a second complete remission. In 2 of the 16 patients, a serious but completely reversible hemolytic-uremic syndrome developed during the second cycle of treatment with BL22. Common toxic effects included transient hypoalbuminemia and elevated aminotransferase levels. CONCLUSIONS: BL22 can induce complete remissions in patients with hairy-cell leukemia that is resistant to treatment with purine analogues.
Authors: Richard R Furman; Michael L Grossbard; Jeffrey L Johnson; Andrew L Pecora; Peter A Cassileth; Sin-Ho Jung; Bruce A Peterson; Lee M Nadler; Arnold Freedman; Ruthee-Lu Bayer; Nancy L Bartlett; David D Hurd; Bruce D Cheson Journal: Leuk Lymphoma Date: 2011-01-28
Authors: Viola Biberacher; Thomas Decker; Madlen Oelsner; Michaela Wagner; Christian Bogner; Burkhard Schmidt; Robert J Kreitman; Christian Peschel; Ira Pastan; Christian Meyer Zum Büschenfelde; Ingo Ringshausen Journal: Haematologica Date: 2011-12-16 Impact factor: 9.941
Authors: Zhuqing Li; Sankaranarayana P Mahesh; De Fen Shen; Baoying Liu; Willie O Siu; Frank S Hwang; Qing-Chen Wang; Chi-Chao Chan; Ira Pastan; Robert B Nussenblatt Journal: Cancer Res Date: 2006-11-01 Impact factor: 12.701