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Published in: International Journal of Hematology 3/2009

01-10-2009 | Original Article

Suppressed neutrophil function in children with acute lymphoblastic leukemia

Authors: Fumiko Tanaka, Hiroaki Goto, Tomoko Yokosuka, Masakatsu Yanagimachi, Ryosuke Kajiwara, Takuya Naruto, Shigeru Nishimaki, Shumpei Yokota

Published in: International Journal of Hematology | Issue 3/2009

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Abstract

Infection is a major obstacle in cancer chemotherapy. Neutropenia has been considered to be the most important risk factor for severe infection; however, other factors, such as impaired neutrophil function, may be involved in susceptibility to infection in patients undergoing chemotherapy. In this study, we analyzed neutrophil function in children with acute lymphoblastic leukemia (ALL). Whole blood samples were obtained from 16 children with ALL at diagnosis, after induction chemotherapy, and after consolidation chemotherapy. Oxidative burst and phagocytic activity of neutrophils were analyzed by flow cytometry. Oxidative burst of neutrophils was impaired in ALL patients. The percentage of neutrophils with normal oxidative burst after PMA stimulation was 59.0 ± 13.2 or 70.0 ± 21.0% at diagnosis or after induction chemotherapy, respectively, which was significantly lower compared with 93.8 ± 6.1% in healthy control subjects (P = 0.00004, or 0.002, respectively); however, this value was normal after consolidation chemotherapy. No significant differences were noted in phagocytic activity in children with ALL compared with healthy control subjects. Impaired oxidative burst of neutrophils may be one risk factor for infections in children with ALL, especially in the initial periods of treatment.
Literature
1.
go back to reference Christensen MS, Heyman M, Mottonen M, Zeller B, Jonmundsson G, Hasle H. Nordic Society of Paediatric Haematology and Oncology (NOPHO): treatment-related death in childhood acute lymphoblastic leukaemia in the Nordic countries: 1992–2001. Br J Haematol. 2005;131:50–8.CrossRefPubMed Christensen MS, Heyman M, Mottonen M, Zeller B, Jonmundsson G, Hasle H. Nordic Society of Paediatric Haematology and Oncology (NOPHO): treatment-related death in childhood acute lymphoblastic leukaemia in the Nordic countries: 1992–2001. Br J Haematol. 2005;131:50–8.CrossRefPubMed
2.
go back to reference Rubnitz JE, Lensing S, Zhou Y, Sandlund JT, Razzouk BI, Ribeiro RC, et al. Death during induction therapy and first remission of acute leukemia in childhood: the St. Jude experience. Cancer. 2004;101:1677–84.CrossRefPubMed Rubnitz JE, Lensing S, Zhou Y, Sandlund JT, Razzouk BI, Ribeiro RC, et al. Death during induction therapy and first remission of acute leukemia in childhood: the St. Jude experience. Cancer. 2004;101:1677–84.CrossRefPubMed
3.
go back to reference Hargrave DR, Hann II, Richards SM, Hill FG, Lilleyman JS, Kinsey S, et al. Medical Research Council Working Party for Childhood Leukaemia: progressive reduction in treatment-related deaths in Medical Research Council childhood lymphoblastic leukaemia trials from 1980 to 1997 (UKALL VIII, X and XI). Br J Haematol. 2001;112:293–9.CrossRefPubMed Hargrave DR, Hann II, Richards SM, Hill FG, Lilleyman JS, Kinsey S, et al. Medical Research Council Working Party for Childhood Leukaemia: progressive reduction in treatment-related deaths in Medical Research Council childhood lymphoblastic leukaemia trials from 1980 to 1997 (UKALL VIII, X and XI). Br J Haematol. 2001;112:293–9.CrossRefPubMed
4.
go back to reference Offidani M, Corvatta L, Malerba L, Marconi M, Leoni P. Infectious complications in adult acute lymphoblastic leukemia (ALL): experience at one single center. Leuk Lymphoma. 2004;45:1617–21.CrossRefPubMed Offidani M, Corvatta L, Malerba L, Marconi M, Leoni P. Infectious complications in adult acute lymphoblastic leukemia (ALL): experience at one single center. Leuk Lymphoma. 2004;45:1617–21.CrossRefPubMed
5.
go back to reference Annino L, Vegna ML, Camera A, Specchia G, Visani G, Fioritoni G, et al. Treatment of adult acute lymphoblastic leukemia (ALL): long-term follow-up of the GIMEMA ALL 0288 randomized study. Blood. 2002;99:863–71.CrossRefPubMed Annino L, Vegna ML, Camera A, Specchia G, Visani G, Fioritoni G, et al. Treatment of adult acute lymphoblastic leukemia (ALL): long-term follow-up of the GIMEMA ALL 0288 randomized study. Blood. 2002;99:863–71.CrossRefPubMed
6.
go back to reference Bodey GP. Infection in cancer patients: a continuing association. Am J Med. 1986;81:11–26. Review.CrossRefPubMed Bodey GP. Infection in cancer patients: a continuing association. Am J Med. 1986;81:11–26. Review.CrossRefPubMed
7.
go back to reference Yamamoto K, Sasada M, Nishiyama H, Uchida M, Sawada H, Nakamura T, et al. Ingestion and killing of bacteria by neutrophils from patients with leukemia: a new method for evaluating phagocyte function at short incubation. Acta Haematol Jpn. 1982;45:56–65. Yamamoto K, Sasada M, Nishiyama H, Uchida M, Sawada H, Nakamura T, et al. Ingestion and killing of bacteria by neutrophils from patients with leukemia: a new method for evaluating phagocyte function at short incubation. Acta Haematol Jpn. 1982;45:56–65.
8.
go back to reference Hubel K, Hegener K, Schnell R, Mansmann G, Oberhauser F, Staib P, et al. Suppressed neutrophil function as a risk factor for severe infection after cytotoxic chemotherapy in patients with acute nonlymphocytic leukemia. Ann Hematol. 1999;78:73–7.CrossRefPubMed Hubel K, Hegener K, Schnell R, Mansmann G, Oberhauser F, Staib P, et al. Suppressed neutrophil function as a risk factor for severe infection after cytotoxic chemotherapy in patients with acute nonlymphocytic leukemia. Ann Hematol. 1999;78:73–7.CrossRefPubMed
9.
go back to reference Hofmann WK, Stauch M, Hoffken K. Impaired granulocytic function in patients with acute leukaemia: only partial normalisation after successful remission-inducing treatment. J Cancer Res Clin Oncol. 1998;124:113–6.CrossRefPubMed Hofmann WK, Stauch M, Hoffken K. Impaired granulocytic function in patients with acute leukaemia: only partial normalisation after successful remission-inducing treatment. J Cancer Res Clin Oncol. 1998;124:113–6.CrossRefPubMed
10.
go back to reference Lejeune M, Ferster A, Cantinieaux B, Sariban E. Prolonged but reversible neutrophil dysfunctions differentially sensitive to G-CSF in children with ALL. Br J Haematol. 1998;102:1284–91.CrossRefPubMed Lejeune M, Ferster A, Cantinieaux B, Sariban E. Prolonged but reversible neutrophil dysfunctions differentially sensitive to G-CSF in children with ALL. Br J Haematol. 1998;102:1284–91.CrossRefPubMed
11.
go back to reference Manabe A, Ohara A, Hasegawa D, Koh K, Saito T, Kiyokawa N. Significance of the complete clearance of peripheral blasts after 7 days of prednisolone treatment in children with acute lymphoblastic leukemia: the Tokyo Children’s Cancer Study Group Study L99-15. Haematologica. 2008;93:1155–60.CrossRefPubMed Manabe A, Ohara A, Hasegawa D, Koh K, Saito T, Kiyokawa N. Significance of the complete clearance of peripheral blasts after 7 days of prednisolone treatment in children with acute lymphoblastic leukemia: the Tokyo Children’s Cancer Study Group Study L99-15. Haematologica. 2008;93:1155–60.CrossRefPubMed
12.
go back to reference Bass DA, Parce JW, Dechatelet LR, Szejda P, Seeds MC, Thomas M. Flow cytometric studies of oxidative product formation by neutrophils: a graded response to membrane stimulation. J Immunol. 1983;130:1910–7.PubMed Bass DA, Parce JW, Dechatelet LR, Szejda P, Seeds MC, Thomas M. Flow cytometric studies of oxidative product formation by neutrophils: a graded response to membrane stimulation. J Immunol. 1983;130:1910–7.PubMed
13.
go back to reference Walrand S, Valeix S, Rodriguez C, Ligot P, Chassagne J, Vasson MP. Flow cytometry study of polymorphonuclear neutrophil oxidative burst: a comparison of three fluorescent probes. Clin Chim Acta. 2003;331:103–10.CrossRefPubMed Walrand S, Valeix S, Rodriguez C, Ligot P, Chassagne J, Vasson MP. Flow cytometry study of polymorphonuclear neutrophil oxidative burst: a comparison of three fluorescent probes. Clin Chim Acta. 2003;331:103–10.CrossRefPubMed
14.
go back to reference Dunn PA, Tyrer HW. Quantitation of neutrophil phagocytosis, using fluorescent latex beads: correlation of microscopy and flow cytometry. J Lab Clin Med. 1981;98:374–81.PubMed Dunn PA, Tyrer HW. Quantitation of neutrophil phagocytosis, using fluorescent latex beads: correlation of microscopy and flow cytometry. J Lab Clin Med. 1981;98:374–81.PubMed
15.
go back to reference Katsimpardi K, Papadakis V, Pangalis A, Parcharidou A, Panagiotou JP, Soutis M, et al. Infections in a pediatric patient cohort with acute lymphoblastic leukemia during the entire course of treatment. Support Care Cancer. 2006;14:277–84.CrossRefPubMed Katsimpardi K, Papadakis V, Pangalis A, Parcharidou A, Panagiotou JP, Soutis M, et al. Infections in a pediatric patient cohort with acute lymphoblastic leukemia during the entire course of treatment. Support Care Cancer. 2006;14:277–84.CrossRefPubMed
16.
go back to reference Tsurumi H, Shimazaki M, Takahashi T, Moriwaki H, Muto Y. Flow cytometric determination of active oxygen (hydroperoxide) produced by peripheral blood neutrophils in patients with hematological disorders. Int J Hematol. 1993;57:213–9.PubMed Tsurumi H, Shimazaki M, Takahashi T, Moriwaki H, Muto Y. Flow cytometric determination of active oxygen (hydroperoxide) produced by peripheral blood neutrophils in patients with hematological disorders. Int J Hematol. 1993;57:213–9.PubMed
17.
go back to reference Lewkowicz P, Lewkowicz N, Sasiak A, Tchorzewski H. Lipopolysaccharide-activated CD4+CD25+ T regulatory cells inhibit neutrophil function and promote their apoptosis and death. J Immunol. 2006;177:7155–63.CrossRefPubMed Lewkowicz P, Lewkowicz N, Sasiak A, Tchorzewski H. Lipopolysaccharide-activated CD4+CD25+ T regulatory cells inhibit neutrophil function and promote their apoptosis and death. J Immunol. 2006;177:7155–63.CrossRefPubMed
18.
go back to reference Wu S, Gessner R, von Stackelberg A, Kirchner R, Henze G, Seeger K. Cytokine/cytokine receptor gene expression in childhood acute lymphoblastic leukemia: correlation of expression and clinical outcome at first disease recurrence. Cancer. 2005;103:1054–63.CrossRefPubMed Wu S, Gessner R, von Stackelberg A, Kirchner R, Henze G, Seeger K. Cytokine/cytokine receptor gene expression in childhood acute lymphoblastic leukemia: correlation of expression and clinical outcome at first disease recurrence. Cancer. 2005;103:1054–63.CrossRefPubMed
19.
go back to reference Kuga S, Otsuka T, Niiro H, Nunoi H, Nemoto Y, Nakano T, et al. Suppression of superoxide anion production by interleukin-10 is accompanied by a downregulation of the genes for subunit proteins of NADPH oxidase. Exp Hematol. 1996;24:151–7.PubMed Kuga S, Otsuka T, Niiro H, Nunoi H, Nemoto Y, Nakano T, et al. Suppression of superoxide anion production by interleukin-10 is accompanied by a downregulation of the genes for subunit proteins of NADPH oxidase. Exp Hematol. 1996;24:151–7.PubMed
Metadata
Title
Suppressed neutrophil function in children with acute lymphoblastic leukemia
Authors
Fumiko Tanaka
Hiroaki Goto
Tomoko Yokosuka
Masakatsu Yanagimachi
Ryosuke Kajiwara
Takuya Naruto
Shigeru Nishimaki
Shumpei Yokota
Publication date
01-10-2009
Publisher
Springer Japan
Published in
International Journal of Hematology / Issue 3/2009
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-009-0412-4

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