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Advances in treatment for chronic granulomatous disease

Immunologic Research volume 43, pages 77–84 (2009)Cite this article

Abstract

Chronic granulomatous disease (CGD) is a rare congenital disorder resulting from a failure of neutrophils to produce oxidases. Patients are therefore prone to recurrent infections from various organisms including fungi and atypical bacteria. The mortality in patients with the X-linked form of CGD, the most common type, ranges from 3% to 5% per year and although management of infections has improved with advances in antimicrobial therapies, better methods are needed to be able to cure these patients. Peripheral blood stem cell or bone marrow transplantation, while curative, is not widely used due to the episodic nature of the infections and the belief by many that conservative management is preferable to the risks of transplantation. Still, as will be discussed, improvements in the field are making allogenic transplantation more desirable and tilting the risk benefit ratio in favor of this modality. Additionally, gene therapy, which has been a long touted method to cure CGD, has within the last 5–10 years become more and more of a reality and may be realized by the end of this decade.

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References

  1. Ahlin A, et al. Prevalence, genetics and clinical presentation of chronic granulomatous disease in Sweden. Acta Paediatr. 1995;84(12):1386–94.

    PubMed  Article  CAS  Google Scholar 

  2. Winkelstein JA, et al. Chronic granulomatous disease. Report on a national registry of 368 patients. Medicine (Baltimore). 2000;79(3):155–69.

    Article  CAS  Google Scholar 

  3. Roos D. The genetic basis of chronic granulomatous disease. Immunol Rev. 1994;138:121–57.

    PubMed  Article  CAS  Google Scholar 

  4. Segal BH, et al. Genetic, biochemical, and clinical features of chronic granulomatous disease. Medicine (Baltimore). 2000;79(3):170–200.

    Article  CAS  Google Scholar 

  5. De Ravin SS, et al. Sarcoidosis in chronic granulomatous disease. Pediatrics. 2006;117(3):e590–5.

    PubMed  Article  Google Scholar 

  6. Strate M, Brandrup F, Wang P. Discoid lupus erythematosus-like skin lesions in a patient with autosomal recessive chronic granulomatous disease. Clin Genet. 1986;30(3):184–90.

    PubMed  CAS  Google Scholar 

  7. Manzi S, et al. Systemic lupus erythematosus in a boy with chronic granulomatous disease: case report and review of the literature. Arthritis Rheum. 1991;34(1):101–5.

    PubMed  Article  CAS  Google Scholar 

  8. Lee BW, Yap HK. Polyarthritis resembling juvenile rheumatoid arthritis in a girl with chronic granulomatous disease. Arthritis Rheum. 1994;37(5):773–6.

    PubMed  Article  CAS  Google Scholar 

  9. Ortiz-Romero PL, et al. Lupus like lesions in a patient with X-linked chronic granulomatous disease and recombinant X chromosome. Dermatology. 1997;195(3):280–3.

    PubMed  CAS  Article  Google Scholar 

  10. Bendhack ML, et al. Chronic granulomatous disease masquerading as a bladder tumor: a potential source of diagnostic error. Eur Urol. 1997;32(3):380–4.

    PubMed  CAS  Google Scholar 

  11. al-Tawil YS, et al. Steroid-responsive esophageal obstruction in a child with chronic granulomatous disease (CGD). J Pediatr Gastroenterol Nutr. 1996;23(2):182–5.

    PubMed  Article  CAS  Google Scholar 

  12. Lindahl JA, Williams FH, Newman SL. Small bowel obstruction in chronic granulomatous disease. J Pediatr Gastroenterol Nutr. 1984;3(4):637–40.

    PubMed  CAS  Article  Google Scholar 

  13. Johnson FE, et al. Gastric outlet obstruction due to X-linked chronic granulomatous disease. Surgery. 1975;78(2):217–23.

    PubMed  CAS  Google Scholar 

  14. Gallin JI, et al. Itraconazole to prevent fungal infections in chronic granulomatous disease. N Engl J Med. 2003;348(24):2416–22.

    PubMed  Article  CAS  Google Scholar 

  15. Weening RS, Leitz GJ, Seger RA. Recombinant human interferon-gamma in patients with chronic granulomatous disease—European follow up study. Eur J Pediatr. 1995;154(4):295–8.

    PubMed  CAS  Google Scholar 

  16. Marciano BE, et al. Long-term interferon-gamma therapy for patients with chronic granulomatous disease. Clin Infect Dis. 2004;39(5):692–9.

    PubMed  Article  CAS  Google Scholar 

  17. Ohga S, et al. Interferon-gamma therapy for infection control in chronic granulomatous disease. Acta Paediatr Jpn. 1995;37(3):315–20.

    PubMed  CAS  Google Scholar 

  18. Woodman RC, et al. Prolonged recombinant interferon-gamma therapy in chronic granulomatous disease: evidence against enhanced neutrophil oxidase activity. Blood. 1992;79(6):1558–62.

    PubMed  CAS  Google Scholar 

  19. The International Chronic Granulomatous Disease Cooperative Study Group. A controlled trial of interferon gamma to prevent infection in chronic granulomatous disease. N Engl J Med. 1991;324(8):509–16.

    Google Scholar 

  20. Tisdale JF, et al. Ex vivo expansion of genetically marked rhesus peripheral blood progenitor cells results in diminished long-term repopulating ability. Blood. 1998;92(4):1131–41.

    PubMed  CAS  Google Scholar 

  21. Kiem HP, et al. Improved gene transfer into baboon marrow repopulating cells using recombinant human fibronectin fragment CH-296 in combination with interleukin-6, stem cell factor, FLT-3 ligand, and megakaryocyte growth and development factor. Blood. 1998;92(6):1878–86.

    PubMed  CAS  Google Scholar 

  22. Cavazzana-Calvo M, et al. Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease [see comments]. Science. 2000;288(5466):669–72.

    PubMed  Article  CAS  Google Scholar 

  23. Hacein-Bey-Abina S, et al. A serious adverse event after successful gene therapy for X-linked severe combined immunodeficiency. N Engl J Med. 2003;348(3):255–6.

    PubMed  Article  Google Scholar 

  24. Malech HL, et al. Extended production of oxidase normal neutrophils in X-linked chronic granulomatous disease (CGD) following gene therapy with gp91phos transduced CD34+ cells. Blood. 1998;92(10(Suppl)):690a.

    Google Scholar 

  25. Malech HL, et al. Prolonged production of NADPH oxidase-corrected granulocytes after gene therapy of chronic granulomatous disease. Proc Natl Acad Sci USA. 1997;94(22):12133–8.

    PubMed  Article  CAS  Google Scholar 

  26. Ott MG, et al. Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1. Nat Med. 2006;12(4):401–9.

    PubMed  Article  CAS  Google Scholar 

  27. Calmels B, et al. Recurrent retroviral vector integration at the MDS1-EVI1 locus in non-human primate hematopoietic cells. Blood. 2005;106(7):2530–3.

    PubMed  Article  CAS  Google Scholar 

  28. Roesler J, et al. Third-generation, self-inactivating gp91(phox) lentivector corrects the oxidase defect in NOD/SCID mouse-repopulating peripheral blood-mobilized CD34+ cells from patients with X-linked chronic granulomatous disease. Blood. 2002;100(13):4381–90.

    PubMed  Article  CAS  Google Scholar 

  29. Brenner S, et al. Concentrated RD114-pseudotyped MFGS-gp91phox vector achieves high levels of functional correction of the chronic granulomatous disease oxidase defect in NOD/SCID/{beta}2-microglobulin−/− repopulating mobilized human peripheral blood CD34+ cells. Blood. 2003;102(8):2789–97.

    PubMed  Article  CAS  Google Scholar 

  30. Horwitz ME, et al. Treatment of chronic granulomatous disease with nonmyeloablative conditioning and a T-cell-depleted hematopoietic allograft. N Engl J Med. 2001;344(12):881–8.

    PubMed  Article  CAS  Google Scholar 

  31. Seger RA, et al. Treatment of chronic granulomatous disease with myeloablative conditioning and an unmodified hemopoietic allograft: a survey of the European experience, 1985–2000. Blood. 2002;100(13):4344–50.

    PubMed  Article  CAS  Google Scholar 

  32. Bhattacharya A, et al. Successful umbilical cord blood stem cell transplantation for chronic granulomatous disease. Bone Marrow Transplant. 2003;31(5):403–5.

    PubMed  Article  CAS  Google Scholar 

  33. Watanabe C, et al. Successful unrelated bone marrow transplantation for a patient with chronic granulomatous disease and associated resistant pneumonitis and Aspergillus osteomyelitis. Bone Marrow Transplant. 2001;28(1):83–7.

    PubMed  Article  CAS  Google Scholar 

  34. Ozsahin H, et al. Successful treatment of invasive aspergillosis in chronic granulomatous disease by bone marrow transplantation, granulocyte colony-stimulating factor-mobilized granulocytes, and liposomal amphotericin-B. Blood. 1998;92(8):2719–24.

    PubMed  CAS  Google Scholar 

  35. Kobayashi S, et al. Clinical features and prognoses of 23 patients with chronic granulomatous disease followed for 21 years by a single hospital in Japan. Eur J Pediatr. 2008.

  36. Kansoy S, et al. Successful bone marrow transplantation in an 8-month-old patient with chronic granulomatous disease. Turk J Pediatr. 2006;48(3):253–5.

    PubMed  Google Scholar 

  37. Schuetz C, et al. Successful unrelated bone marrow transplantation in a child with chronic granulomatous disease complicated by pulmonary and cerebral granuloma formation. Eur J Pediatr. 2007;166(8):785–8.

    PubMed  Article  Google Scholar 

  38. Sastry J, et al. Allogeneic bone marrow transplantation with reduced intensity conditioning for chronic granulomatous disease complicated by invasive Aspergillus infection. Pediatr Blood Cancer. 2006;47(3):327–9.

    PubMed  Article  Google Scholar 

  39. Gungor T, et al. Successful low toxicity hematopoietic stem cell transplantation for high-risk adult chronic granulomatous disease patients. Transplantation. 2005;79(11):1596–606.

    PubMed  Article  Google Scholar 

  40. Leung T, et al. Bone marrow transplantation for chronic granulomatous disease: long-term follow-up and review of literature. Bone Marrow Transplant. 1999;24(5):567–70.

    PubMed  Article  CAS  Google Scholar 

  41. Ho CM, et al. Successful bone marrow transplantation in a child with X-linked chronic granulomatous disease. Bone Marrow Transplant. 1996;18(1):213–15.

    PubMed  CAS  Google Scholar 

  42. Hasegawa D, et al. Successful treatment of chronic granulomatous disease with fludarabine-based reduced-intensity conditioning and unrelated bone marrow transplantation. Int J Hematol. 2008;87(1):88–90.

    PubMed  Article  CAS  Google Scholar 

  43. Parikh SH, et al. Correction of chronic granulomatous disease after second unrelated-donor umbilical cord blood transplantation. Pediatr Blood Cancer. 2007;49(7):982–4.

    PubMed  Article  Google Scholar 

  44. Suzuki N, et al. Treatment of McLeod phenotype chronic granulomatous disease with reduced-intensity conditioning and unrelated-donor umbilical cord blood transplantation. Int J Hematol. 2007;85(1):70–2.

    PubMed  Article  Google Scholar 

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Author information

Affiliations

  1. National Institutes of Health, Building 10-Room 6-3752, 10 Center Drive, Bethesda, Maryland, 20892, USA

    Elizabeth M. Kang

  2. National Institutes of Health, Building 10-Room 5-3750, 10 Center Drive, Bethesda, Maryland, 20892, USA

    Harry L. Malech

Authors
  1. Elizabeth M. Kang
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  2. Harry L. Malech
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Correspondence to Elizabeth M. Kang.

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Kang, E.M., Malech, H.L. Advances in treatment for chronic granulomatous disease. Immunol Res 43, 77–84 (2009). https://doi.org/10.1007/s12026-008-8051-z

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  • DOI: https://doi.org/10.1007/s12026-008-8051-z

Keywords

  • Chronic granulomatous disease
  • Gene therapy
  • Allogeneic transplantation
  • Autoimmune complications
  • Antibiotic prophylaxis
  • Interferon gamma