title: Efficacy of the anti-CD22 recombinant immunotoxin BL22 in chemotherapy-resistant hairy-cell leukemia.
abstract: 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.affiliation: Laboratory of Molecular Biology, National Cancer Institute, Bethesda, MD 20892, USA. kreitmar@mail.nih.gov
authors.forename: R J
authors.initials: RJ
authors.lastname: Kreitman
authors.forename: W H
authors.initials: WH
authors.lastname: Wilson
authors.forename: K
authors.initials: K
authors.lastname: Bergeron
authors.forename: M
authors.initials: M
authors.lastname: Raggio
authors.forename: M
authors.initials: M
authors.lastname: Stetler-Stevenson
authors.forename: D J
authors.initials: DJ
authors.lastname: FitzGerald
authors.forename: I
authors.initials: I
authors.lastname: Pastan
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D017338:Cladribine / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004768:Enterotoxins; D005098:Exotoxins / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006463:Hemolytic-Uremic Syndrome / Q000139:chemically induced; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage* / Q000009:adverse effects; D007943:Leukemia, Hairy Cell / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011549:Pseudomonas; D012008:Recurrence; D012074:Remission Induction / Q000379:methods
chemical_list: D000906:Antibodies; D000970:Antineoplastic Agents; D004768:Enterotoxins; D005098:Exotoxins; D000922:Immunotoxins; C431326:RFB4(dsFv)-PE38 recombinant immunotoxin; D017338:Cladribine