Approach to the patient after relapse of hairy cell leukemia.
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.
Kreitman
Robert J
RJ
Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. kreitmar@mail.nih.gov
Fitzgerald
David J P
DJ
Pastan
Ira
I
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
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