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Related Experiment Videos

BL22 and lymphoid malignancies.

Robert J Kreitman1, Ira Pastan

  • 1Centers for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 37, Room 5124b, Bethesda, MD 20892-4255, USA. kreitmar@mail.nih.gov

Best Practice & Research. Clinical Haematology
|September 26, 2006
PubMed
Summary
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BL22, an anti-CD22 immunotoxin, shows significant activity in chemoresistant hairy-cell leukemia, inducing complete remission in 61% of patients. Further trials are underway to mitigate dose-limiting hemolytic uremic syndrome.

Area of Science:

  • Oncology
  • Immunology
  • Pharmacology

Background:

  • Hairy-cell leukemia (HCL) is often chemoresistant.
  • BL22 is a novel recombinant immunotoxin targeting the CD22 antigen.

Purpose of the Study:

  • To evaluate the safety and efficacy of BL22 in patients with chemoresistant HCL.
  • To investigate the mechanism of action and dose-limiting toxicities of BL22.

Main Methods:

  • Phase I clinical trial of BL22 in patients with HCL.
  • BL22 mechanism involves CD22 binding, endocytosis, cytoplasmic translocation, and elongation factor 2 inactivation.

Main Results:

  • BL22 demonstrated high activity in chemoresistant HCL, with 61% of 31 patients achieving complete remission.

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  • Cytopenias improved in responders.
  • Reversible hemolytic uremic syndrome (HUS) was the dose-limiting toxicity, observed in cycles 2-3.
  • Conclusions:

    • BL22 is an active agent in chemoresistant HCL.
    • Modified protocols are being investigated in ongoing Phase II HCL and Phase I chronic lymphocytic leukemia (CLL) and acute lymphocytic leukemia (ALL) trials to prevent HUS.