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Decrease of CD4+ and B-Lymphocyte Populations Is Not Associated with Severe Infectious Complications in Children with Acute Lymphoblastic Leukemia during Maintenance

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Abstract

The suppression of lymphopoiesis and immune competence during the maintenance phase in children with acute lymphoblastic leukemia (ALL) and the occurrence of infectious complications remain an unexplored area. In this study we assessed lymphocyte subpopulation disturbances during maintenance for childhood ALL along with the incidence, type, and severity of infections that occur during that period in the absence of neutropenia. Twenty-eight children (13 boys, 15 girls) with ALL aged 3-14 years (median 7 years) and treated according to the ALL-BFM 90/95 protocol were studied during maintenance for ALL. Complete white blood cell (WBC) counts and peripheral blood lymphocyte (PBL) analyses were performed. Major lymphocyte subsets (CD19+, CD3+CD4+, CD3+CD8+, CD3-CD16+CD56+, CD45RA+, CD45RO+) and markers of T-cell activation (CD25, CD38, CD69, HLA-DR) were analyzed with flow cytometry. Serum immunoglobulin G (IgG), IgA, and IgM levels were measured by a nephelometric assay. All infectious episodes during the study period were recorded in detail. Additionally, 41 age-matched immunocompetent children were used as controls. Absolute WBC counts (median, 3627/µL) and PBL counts (median, 1206/µL) were significantly below the age-adjusted control values (7400/µL and 2673/µL, respectively; P < 0001). B-lymphocyte, total CD4+, and memory CD4+ (CD4+CD45RO+) subsets were also significantly decreased (33/µL versus 377/µL [P <.0001], 531/µL versus 1045/µL [P <.01], and 80/µL versus 299/µL [P <.001], respectively). Significantly lower immunoglobulin levels were found in all patients. Twenty-two of the 28 patients presented with 74 episodes of a variety of minor infections (mostly respiratory viral [39], skin [7], and gastrointestinal [3]), none demanding prolonged hospital treatment. Our findings demonstrate a profound immunosuppression throughout maintenance therapy in children with ALL that has no major clinical impact in terms of increased incidence or severity of systemic infections.

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References

  1. Lee JW, Pizzo PA. Management of specific problems in children with leukemias and lymphomas. In: Patrick CC, ed. Infections in Immuno-compromised Infants and Children. New York, NY: Churchill Livingstone; 1992:195–214.

    Google Scholar 

  2. Pizzo PA Infectious complications in the child with cancer, I: pathophysiology of the compromised host and the initial evaluation and management of the febrile cancer patient. J Pediatr. 1981; 98:341–354.

    Article  PubMed  CAS  Google Scholar 

  3. Pizzo PA, Rubin M, Freifeld A, Wash TJ. The child with cancer and infection, I: empiric therapy for fever and neutropenia, and preventive strategies. J Pediatr. 1991;119:679–694.

    Article  PubMed  CAS  Google Scholar 

  4. Lex C, Korholz D, Kohlmuller B, et al. Infectious complications in children with acute lymphoblastic leukemia and T-cell lymphoma: a rationale for tailored supportive care. Support Care Cancer. 2001; 9:514–521.

    Article  PubMed  CAS  Google Scholar 

  5. Pizzo PA, Rubin M, Freifeld A, Walsh J. The child with cancer and infection, II: nonbacterial infections. J Pediatr. 1991;119:845–857.

    Article  PubMed  CAS  Google Scholar 

  6. Gross RA, Lee H, Wolff JA, Hall CB, Minnefore AB, Lazicki ME. Influenza immunization in immunosuppressed children. J Pediatr. 1978;92:30–35.

    Article  PubMed  CAS  Google Scholar 

  7. Polychronopoulou-Androulakaki S, Panagiotou JP, Kostaridou S, Kyratzopoulou A, Haidas S. Immune response of immunocompromised children with malignancies to a recombinant hepatitis B vaccine. Pediatr Hematol Oncol. 1996;13:425–431.

    Article  PubMed  CAS  Google Scholar 

  8. Lovat PE, Robinson JH, Windebank KP, Kernahan J, Watson JG. Serial study of T lymphocytes in childhood leukemia during remission. Pediatr Hematol Oncol. 1993;10:129–139.

    Article  PubMed  CAS  Google Scholar 

  9. Caver TE, Slobod KS, Flynn PM, et al. Profound abnormality of B/T lymphocyte ratio during chemotherapy for pediatric acute lymphoblastic leukemia. Leukemia. 1998;12:619–622.

    Article  PubMed  CAS  Google Scholar 

  10. Moritz B, Eder J, Meister B, Heitger A. Intact T-cell regenerative capacity in childhood acute lymphoblastic leukemia after remission induction therapy. Med Pediatr Oncol. 2001;36:283–289.

    Article  PubMed  CAS  Google Scholar 

  11. Katevas P, Lembesopoulos C, Kamitaki C, et al. Establishment of normal ranges of lymphocyte subpopulations in cord blood and in peripheral blood in infants and in children. Haema. 1999;2:145–151.

    Google Scholar 

  12. Erkeller-Yuksei FM, Deneys V, Yuksel B, et al. Age-related changes in human blood lymphocyte subpopulations. J Pediatr. 1992;120:216–222.

    Article  Google Scholar 

  13. Pui C-H, Evans WE. Acute lymphoblastic leukemia. N Engl J Med. 1998;339:605–615.

    Article  PubMed  CAS  Google Scholar 

  14. Borzy MS, Ridgway D. Prolonged defects of interleukin-2 production, responsiveness, and receptor expression in patients with acute lymphoblastic leukemia. Blood. 1989;73:1608–1614.

    PubMed  CAS  Google Scholar 

  15. Komada Y, Zhang SL, Zhou YW, et al. Cellular immunosuppression in children with acute lymphoblastic leukemia: effect of consolidation chemotherapy. Cancer Immunol Immunother. 1992;35:271–276.

    Article  PubMed  CAS  Google Scholar 

  16. Papadakis V, Panagiotou JP, Polychronopoulou-Androulakaki S, et al. Results of childhood acute lymphoblastic leukaemia treatment in Greek patients using a BFM-based protocol. Haema. 2003;6:208–216.

    Google Scholar 

  17. Alanco S, Pellinieri T-T, Salmi TV. Recovery of blood B-lymphocytes and serum immunoglobulins after chemotherapy for childhood acute lymphoblastic leukemia. Cancer. 1992;69:1481–1486.

    Article  Google Scholar 

  18. Masur H, Ognibene FP, Yarchoan R, et al. CD4 counts as predictors of opportunistic pneumonias in human immunodeficiency virus (HIV) infection. Ann Intern Med. 1989;111:223–231.

    Article  PubMed  CAS  Google Scholar 

  19. Mackall CL, Fleisher TA, Brown MR, et al. Age, thymopoiesis, and CD4+ T-lymphocyte regeneration after intensive chemotherapy. N EnglJ Med. 1995;332:143–149.

    Article  CAS  Google Scholar 

  20. Leino L, Lilius E-M, Nikoskelainen J, Pelliniemi TT, Rajamaki A. The reappearance of 10 differentiation antigens on peripheral blood lymphocytes after allogeneic bone marrow transplantation. Bone Marrow Transplant. 1991;8:339–344.

    PubMed  CAS  Google Scholar 

  21. Smith S, Schiffman G, Karayalcin G, Bonagura V. Immunodeficiency in long-term survivors of acute lymphoblastic leukemia treated with Berlin-Frankfurt-Munster therapy. J Pediatr. 1995;127:68–75.

    Article  PubMed  CAS  Google Scholar 

  22. Layward L, Levinsky RJ, Butler M. Long-term abnormalities in B and T lymphocyte function in children following treatment for acute lymphoblastic leukemia. Br J Haematol. 1981;49:251–258.

    Article  PubMed  CAS  Google Scholar 

  23. Hayns BF, Fauci AS. The differential effect of in vivo hydrocortisone on the kinetics of subpopulations of human peripheral blood thymus-derived lymphocyte. J Clin Invest. 1978;61:703–707.

    Article  Google Scholar 

  24. Boldt DH, Von Hoff DD, Kuhn JG, Hersh M. Effects on human peripheral lymphocytes of in vivo administration of 9-beta-D- arabinofuranosy1-2-fluoradenine-5’-monophosphate (NSC 312887), a new purine antimetabolite. Cancer Res. 1984;144:4661–4666.

    Google Scholar 

  25. Polychronopoulou S, Koutroumba P. Telomere length and telomerase activity variations with advancing age and potential role in childhood malignancies. J Pediatr Hematol Oncol. 2004;26:342–350.

    Article  PubMed  Google Scholar 

  26. Son NH, Murray SH, Yanovski J, Hodes RJ, Weng N. Lineage- specific telomere shortening and unaltered capacity for telomerase expression in human T and B lymphocytes with age. J Immunol. 2000;165:1191–1196.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pediatric Hematology/Oncology, “Aghia Sophia” Children’s Hospital, Ioannou Gennadiou 14A, GR-11521, Athens, Greece

    Stavroula Kostaridou, Sophia Polychronopoulou, Agapi Parcharidou & Stavros Haidas

  2. Department of Immunology and Histocompatibility, “Evangelismos” Hospital, Ioannou Gennadiou 14A, GR-11521, Athens, Greece

    Katherine Psarra, Violetta Kapsimali & Chrysa Papasteriades

  3. Hematology Laboratory and Transfusion Department, Children’s Hospital “Aglaia Kyriakou,”, Ioannou Gennadiou 14A, GR-11521, Athens, Greece

    Prokopis Katevas

Authors
  1. Stavroula Kostaridou
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  2. Sophia Polychronopoulou
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  3. Katherine Psarra
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  4. Violetta Kapsimali
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  5. Agapi Parcharidou
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  6. Prokopis Katevas
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  7. Chrysa Papasteriades
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  8. Stavros Haidas
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Correspondence to Sophia Polychronopoulou.

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Kostaridou, S., Polychronopoulou, S., Psarra, K. et al. Decrease of CD4+ and B-Lymphocyte Populations Is Not Associated with Severe Infectious Complications in Children with Acute Lymphoblastic Leukemia during Maintenance. Int J Hematol 80, 354–360 (2004). https://doi.org/10.1532/IJH97.E0317

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  • DOI: https://doi.org/10.1532/IJH97.E0317

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