Affiliation:
1. From the Departments of Pediatric Oncology, Biostatistics and Computational Biology, and Medical Oncology, Dana-Farber Cancer Institute; Allergy/Immunology, Texas Children's Hospital; Vaccine Research Center, National Institutes of Health; Division of Hematology/Oncology, Children's Hospital, Boston; and Harvard Medical School.
Abstract
Abstract
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 healthy 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. (Blood. 2005; 106:1749-1754)
Publisher
American Society of Hematology
Subject
Cell Biology,Hematology,Immunology,Biochemistry
Reference46 articles.
1. Larson RA, Dodge RK, Linker CA, et al. A randomized controlled trial of filgrastim during remission induction and consolidation chemotherapy for adults with acute lymphoblastic leukemia: CALGB study 9111. Blood.1998;92: 1556-1564.
2. Kantarjian HM, O'Brien S, Smith TL, et al. Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia. J Clin Oncol.2000;18: 547-561.
3. Rubnitz JE, Lensing S, Zhou Y, et al. Death during induction therapy and first remission of acute leukemia in childhood. Cancer.2004;101: 1677-1684.
4. Mackall CL, Fleisher TA, Brown MR, et al. Lymphocyte depletion during treatment with intensive chemotherapy for cancer. Blood.1994;84: 2221-2228.
5. Mackall CL, Fleisher TA, Brown MR, et al. Age, thymopoiesis, and CD4+ T-lymphocyte regeneration after intensive chemotherapy. N Engl J Med.1995;332: 143-149.
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