title: Slow desensitization of imatinib-induced nonimmediate reactions and dynamic changes of drug-specific CD4+CD25+CD134+lymphocytes.
abstract: Imatinib is a tyrosine kinase inhibitor indicated for the treatment of gastrointestinal stromal tumors (GISTs) and certain neoplastic diseases; however, nonimmediate adverse reactions are common.
  
  
  
  To describe the process of imatinib slow desensitization in patients who experienced nonimmediate reactions to imatinib and the dynamic change in drug-specific CD4+CD25+CD134+T-lymphocyte percentages.
  
  
  
  Five patients diagnosed as having GISTs and with a recent history of imatinib-induced nonimmediate reactions (maculopapular exanthema with eosinophilia, exfoliative dermatitis, palmar-plantar erythrodysesthesia, and drug rash with eosinophilia and systemic symptoms) were desensitized using a slow desensitization protocol. The reintroduced imatinib dosage was stepped up every week starting from 10 mg/d and increasing to 25, 50, 75, 100, 150, 200, and 300 mg/d until the target dose of 400 mg/d was achieved. Prednisolone of up to 30 mg/d was allowed if allergic reactions recurred. The percentages of CD4+CD25+CD134+T cells present after incubating peripheral blood mononuclear cells with imatinib, at baseline and after successful desensitization, were analyzed using flow cytometric analysis.
  
  
  
  By using a slow desensitization technique, all patients were able to receive 400 mg/d of imatinib, and prednisolone was gradually tapered off. The percentages of imatinib-induced CD4+CD25+CD134+T cells decreased from a mean (SD) of 11.3% (6.5%) and 13.4% (7.3%) at baseline to 3.2% (0.7%) and 3.0% (1.1%) after successful desensitization, when stimulating peripheral blood mononuclear cells with 1 and 2 μM of imatinib, respectively.
  
  
  
  Slow desensitization is a helpful procedure in treating patients with imatinib-induced nonimmediate reactions other than simple maculopapular exanthema. The reduced percentages of imatinib-induced CD4+CD25+CD134+T cells in these patients may be associated with immune tolerance.
authors: Division of Allergy and Clinical Immunology, Department of Medicine, Faculty of Medicine, and Chulalongkorn Allergy and Clinical Immunology Research Group, Chulalongkorn University, Bangkok, Thailand; King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand. Electronic address: Jettanong.K@chula.ac.th.
authors: Jettanong
authors: J
authors: Klaewsongkram
authors: Division of Allergy and Clinical Immunology, Department of Medicine, Faculty of Medicine, and Chulalongkorn Allergy and Clinical Immunology Research Group, Chulalongkorn University, Bangkok, Thailand.
authors: Pattarawat
authors: P
authors: Thantiworasit
authors: Center of Excellence in Immunology and Immune-Mediated Diseases, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors: Pimpayao
authors: P
authors: Sodsai
authors: Division of Allergy and Clinical Immunology, Department of Medicine, Faculty of Medicine, and Chulalongkorn Allergy and Clinical Immunology Research Group, Chulalongkorn University, Bangkok, Thailand.
authors: Supranee
authors: S
authors: Buranapraditkun
authors: King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.
authors: Pungjai
authors: P
authors: Mongkolpathumrat
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003888:Desensitization, Immunologic; D004342:Drug Hypersensitivity / Q000188:drug therapy / Q000209:etiology; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D000068877:Imatinib Mesylate / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D000068877:Imatinib Mesylate; D011239:Prednisolone