title: Chronic myeloid leukemia patients resistant to or intolerant of interferon alpha and subsequently treated with imatinib show reduced immunoglobulin levels and hypogammaglobulinemia.
abstract: OBJECTIVE
  Imatinib mesylate inhibits ABL tyrosine kinase. This protein serves a complex role in cell cycling and is important in lymphopoiesis. We describe the immunologic findings in patients with chronic myeloid leukemia resistant to or intolerant of interferon (IFN) a who were treated with imatinib. This aspect could be of interest since patients with these characteristics may be exposed to this treatment for long periods.
  
  
  METHODS
  Immunologic and hematologic evaluation (including immunoglobulin levels and parameters of autoimmunity), immunophenotyping analysis of peripheral blood and bone marrow, and cytogenetic bone marrow analysis were performed at sequential time points of the treatment (0, 3, 6, and 9 and 12 months). The relationships among immunologic variables, and between the immunologic findings and response, were investigated.
  
  
  RESULTS
  Hypogammaglobulinemia IgG, IgA and IgM developed in 28%, 14% and 22% of the patients, respectively. Lymphocyte counts decreased significantly along the treatment. No correlation was found between Ig levels and lymphocyte counts or CD4, CD8 or CD19 subpopulations in peripheral blood, nor between Ig levels and bone marrow B-lineage precursors. No autoimmune phenomena were detected. Hypogammaglobulinemia had no clinical repercussions in patients who developed it. The percentage reductions of IgG, IgA and IgM levels were higher in patients with major genetic response to imatinib.
  
  
  CONCLUSIONS
  Hypogammaglobulinemia can develop in as many as 20-25% of patients with chronic myeloid leukemia previously exposed to IFN a and who are then treated with imatinib. The reduction of Ig is greater in patients with a better cytogenetic response, perhaps reflecting that the efficacy of imatinib in blocking BCR-ABL kinase activity runs in parallel with ABL inhibition, leading to a dysregulation of B-lymphocyte function. Close immunologic evaluation is recommended in these patients.
authors.affiliation: Department of Hematology, Hospital Universitario de la Princesa, Madrid, Spain. jlsteegmann@wanadoo.es
authors.forename: Juan Luis
authors.initials: JL
authors.lastname: Steegmann
authors.forename: Gemma
authors.initials: G
authors.lastname: Moreno
authors.forename: Concepción
authors.initials: C
authors.lastname: Aláez
authors.forename: Santiago
authors.initials: S
authors.lastname: Osorio
authors.forename: Asunción
authors.initials: A
authors.lastname: Granda
authors.forename: Rafael
authors.initials: R
authors.lastname: de la Cámara
authors.forename: Eva
authors.initials: E
authors.lastname: Arranz
authors.forename: Fernando Gómez
authors.initials: FG
authors.lastname: Reino
authors.forename: Francisco Rodriguez
authors.initials: FR
authors.lastname: Salvanés
authors.forename: José María
authors.initials: JM
authors.lastname: Fernández-Rañada
authors.forename: Cecilia
authors.initials: C
authors.lastname: Muñoz
mesh_terms: D000293:Adolescent; D000328:Adult; D000361:Agammaglobulinemia / Q000209:etiology* / Q000276:immunology; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015551:Autoimmunity; D001549:Benzamides; D004351:Drug Resistance; D004361:Drug Tolerance; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D016044:Fusion Proteins, bcr-abl; D006801:Humans; D000068877:Imatinib Mesylate; D007136:Immunoglobulins / Q000097:blood; D016130:Immunophenotyping; D016898:Interferon-alpha / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000150:complications / Q000188:drug therapy*; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000145:classification; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D004791:Enzyme Inhibitors; D007136:Immunoglobulins; D016898:Interferon-alpha; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl