Impaired pneumococcal immunity in children after treatment for acute lymphoblastic leukaemia.

Although the substantial risk for invasive pneumococcal disease is well recognized in children after allogeneic stem cell transplantation, little is known about the specific immunity against pneumococci in children after cytotoxic therapy for acute lymphoblastic leukaemia (ALL). We therefore assessed the spontaneous reconstitution of humoral immunity against pneumococcal antigens, of total IgG and the IgG2 subclass, and of lymphocyte subsets in a total of 53 children treated for ALL. None of the patients had received pneumococcal vaccination prior to or after therapy for ALL. At 3 and 9 months after completion of chemotherapy, most patients had levels of specific antibodies to pneumococcal antigens below the presumed threshold of protection and significantly lower than those of age-matched unvaccinated healthy controls. In contrast, at 9 months after completion of therapy, only a minority of patients had immunoglobulin concentrations or lymphocyte subset counts below the age-matched reference value. Our data indicate that patients with ALL who are unvaccinated against pneumococci have a selective immunodeficiency with an impaired antibody protection against pneumococci for up to 9 months after completion of therapy. Therefore, effective prevention, including chemoprophylaxis and active immunization, has to be considered in this patient population.

Age-matched lymphocyte subpopulation reference values in childhood and adolescence: application of exponential regression analysis.

BACKGROUND: Normal values of lymphocyte subpopulations for healthy children and adults have been published in defined age groups exclusively, which results in difficult data interpretation for patients close to the limit of contiguous age group ranges. In addition, normal values for a number of lymphocyte subpopulations have not been established to date. OBJECTIVE: The aim of this study was to develop a model which provides continuous age-dependent reference values. This model was applied for lymphocyte subpopulations such as naïve and memory T cells as well as their activation profile with diagnostic relevance in children and adults. STUDY DESIGN: A total of 100 blood samples, obtained from 80 healthy children and 20 adults were analysed by means of four colour-flow cytometry. Continuous age-dependent reference values were computed based on the residual values in an exponential regression model. RESULTS: We calculated a continuous age-related regression model for both, absolute cell counts and percentages of CD3(+)CD4(+) T helper (T(H)) cells, CD3(+)CD8(+) cytotoxic T cells, CD56(+)CD3(-) natural killer (NK) cells, CD56(+)CD3(+) T cells, CD3(+)CD4(+)CD45RA(+) naïve T(H) cells, CD3(+)CD4(+)CD45RO(+) memory T(H) cells, CD3(+)CD8(+)CD45RA(+)CD28(+) naïve cytotoxic T cells, CD3(+)CD8(+)CD45RO(+) memory cytotoxic T cells, CD3(+)CD8(+)CD69(+) early activated cytotoxic T cells and CD3(+)CD8(+)HLA-DR(+) late activated cytotoxic T cells, respectively, to obtain reference values. CONCLUSION: Based on an exponential regression model, the obtained reference values reflect the continuous maturation of lymphocyte subsets during childhood.