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Blood, 1 September 2005, Vol. 106, No. 5, pp. 1749-1754.
Prepublished online as a Blood First Edition Paper on May 26, 2005; DOI 10.1182/blood-2005-03-1082.
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Submitted March 17, 2005
Accepted May 9, 2005
Antigen-specific T cell memory is preserved in children treated for acute lymphoblastic leukemia
William N Haining*, Donna S Neuberg, Heather L Keczkemethy, John W Evans, Stephen Rivoli, Rebecca Gelman, Howard M Rosenblatt, William T Shearer, Javier Guenaga, Daniel C Douek, Lewis B Silverman, Steven E Sallan, Eva C Guinan, and Lee M Nadler
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Division of Hematology/Oncology, Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA
Department of Biostatistics, Dana-Farber Cancer Institute, Boston, MA, USA
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
Allergy/Immunology, Texas Children's Hospital, Houston, TX, USA
Vaccine Research Center, National Institutes of Health, Bethesda, MD, USA
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA
* Corresponding author; email: nicholas_haining{at}dfci.harvard.edu.
Despite profound T cell immunodeficiency, most patients treated with chemotherapy do not succumb to infection. The basis for residual protective immunity in lymphopenic patients is not known. We prospectively measured T cell numbers, thymopoiesis, and T cell memory in 73 children undergoing a 2-year chemotherapy regimen for acute lymphoblastic leukemia (ALL) and compared them to an age-matched cohort of 805 healthy children. Most patients had profound defects in CD4 and CD8 T cell numbers at diagnosis that did not recover during the 2 years of therapy. Thymic output and the fraction of naive T cells were significantly lower than in normal controls. However, the remaining T cell compartment was enriched for antigen-experienced, memory T cells defined both by phenotype and by function. This relative sparing of T cell memory may, in part, account for the maintenance of protective immunity in lymphopenic patients treated for ALL. Moreover, because the memory T cell compartment is least affected by ALL and its treatment, strategies to induce immunity to pathogens or tumor antigens in cancer patients may be most successful if they seek to expand pre-existing memory T cells.
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