title: Multivariate analysis of the relation between immune dysfunction and treatment intensity in children with acute lymphoblastic leukemia.
abstract: BACKGROUND
  Immunoreconstitution following childhood acute lymphoblastic leukemia (ALL) is a complex process during which various immune functions recover differentially. This process is difficult to elucidate since variables are interrelated and require simultaneous evaluation, rendering conventional statistical methods inappropriate.
  
  
  METHODS
  We used principal components analysis (PCA) and projection of latent structures (PLS) to evaluate immune competence in 32 children treated for ALL. One or 6 months after completion of therapy, the relation between lymphocyte subpopulations, lymphocyte function and response to vaccination with tetanus, diphtheria and hemophilus influenzae, was investigated.
  
  
  RESULTS
  PCA demonstrated that increasing treatment intensity correlated with progressive immune dysfunction. Children treated with high intensity had poor response to vaccination associated with loss of humoral memory, decreased CD4(+) 45RA(+) T-lymphocytes and increased CD5+ B-lymphocytes. Patients treated with intermediate intensity had better preservation of humoral memory but decreased CD4(+) 45RA(+) T-cells. Patients with a low intensity regimen had similar vaccination response and lymphocyte levels as controls.
  
  
  CONCLUSIONS
  Our findings demonstrate the utility of PCA and PLS in detecting hidden structures in complex data and suggest that, even 6 months after therapy, patients treated with intermediate and high intensity have attenuated responses to de novo antigens whereas those with high intensity also respond poorly to recall antigens.
authors.affiliation: Department of Paediatrics, Institution for Clinical Sciences, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Torben
authors.initials: T
authors.lastname: Ek
authors.forename: Mats
authors.initials: M
authors.lastname: Josefson
authors.forename: Jonas
authors.initials: J
authors.lastname: Abrahamsson
mesh_terms: D000293:Adolescent; D000907:Antibodies, Bacterial / Q000276:immunology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D016022:Case-Control Studies; D049109:Cell Proliferation; D002648:Child; D004168:Diphtheria Toxoid / Q000008:administration & dosage; D005260:Female; D005434:Flow Cytometry; D018073:Haemophilus Vaccines / Q000008:administration & dosage; D006801:Humans; D007154:Immune System Diseases / Q000276:immunology*; D007136:Immunoglobulins / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000276:immunology*; D008297:Male; D008962:Models, Theoretical; D015999:Multivariate Analysis; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D025341:Principal Component Analysis; D011379:Prognosis; D013745:Tetanus Toxoid / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000907:Antibodies, Bacterial; D004168:Diphtheria Toxoid; D018073:Haemophilus Vaccines; D007136:Immunoglobulins; D013745:Tetanus Toxoid