Multivariate analysis of the relation between immune dysfunction and treatment intensity in children with acute lymphoblastic leukemia.

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.

Procedure: 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.