title: Approach to the patient after relapse of hairy cell leukemia.
abstract: The current hairy cell leukemia (HCL) treatment is excellent, but evidence of cure with purine analogs cladribine and pentostatin, is lacking. Significant long-term immune suppression, particularly to CD4+ T-cells, and declining complete remission rates with each course, make the identification of new therapies an important goal. The anti-CD20 monoclonal antibody (Mab) rituximab displays significant activity, and, while causing prolonged normal B-cell depletion, spares T-cells. Recombinant immunotoxins, containing an Fv fragment of a Mab fused to truncated Pseudomonas exotoxin, have shown efficacy in HCL resistant to both purine analogs and rituximab. LMB-2 targets CD25 and can induce remission providing the HCL cells are CD25+. All HCL cells display CD22. Recombinant anti-CD22 immunotoxin BL22, targeting CD22, has shown significant efficacy in phase I and II testing, and avoids prolonged suppression of both normal B- and T-cells. An improved high-affinity version of BL22, termed HA22, is currently undergoing phase I testing.
authors.affiliation: Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. kreitmar@mail.nih.gov
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Kreitman
authors.forename: David J P
authors.initials: DJ
authors.lastname: Fitzgerald
authors.forename: Ira
authors.initials: I
authors.lastname: Pastan
mesh_terms: D000465:Algorithms; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017338:Cladribine / Q000627:therapeutic use; D003131:Combined Modality Therapy; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use; D053645:Interleukin-2 Receptor alpha Subunit / Q000037:antagonists & inhibitors / Q000276:immunology; D007943:Leukemia, Hairy Cell / Q000473:pathology / Q000628:therapy*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012008:Recurrence; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C497867:CD22 protein, human; C508017:IL2RA protein, human; D000922:Immunotoxins; D053645:Interleukin-2 Receptor alpha Subunit; D011994:Recombinant Proteins; D051918:Sialic Acid Binding Ig-like Lectin 2; D017338:Cladribine