Skip to main content

Advertisement

Log in

Hematopoetic Stem Cell Transplantation in Neutrophil Disorders: Severe Congenital Neutropenia, Leukocyte Adhesion Deficiency and Chronic Granulomatous Disease

  • Published:
Clinical Reviews in Allergy & Immunology Aims and scope Submit manuscript

    We’re sorry, something doesn't seem to be working properly.

    Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Abstract

Until further progress will occur in the field of gene therapy, the only curative treatment available in severe congenital neutropenia, leukocyte adhesion deficiency, and chronic granulomatous disease is allogeneic hematopoietic stem cell transplantation (HSCT). This review summarizes the current data regarding indications for transplantation in each disease, treatment results using related and unrelated donors, as well as toxicity of HSCT in the above diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Malech HL, Nauseef WM (1997) Primary inherited defects in neutrophil function: etiology and treatment. Semin Hematol 34:279–290

    CAS  PubMed  Google Scholar 

  2. Kostmann R (1956) Infantile genetic agranulocytosis. Acta Paediatrica Scandinavica 45:1–78

    Article  CAS  Google Scholar 

  3. Kostmann R (1975) Infantile genetic agranulocytosis: a review with presentation of ten new cases. Acta Paediatrica Scandinavica 64:362–368

    Article  Google Scholar 

  4. Horwitz MS, Duan Z, Korkmaz B et al (2007) Neutrophil elastase in cyclic and severe congenital neutropenia. Blood 109:1817–1824

    Article  CAS  PubMed  Google Scholar 

  5. Klein C, Grudzien M, Appaswamy G et al (2007) HAX1 deficiency causes autosomal recessive severe CN (Kostmann disease). Nat Genet 39:86–92

    Article  CAS  PubMed  Google Scholar 

  6. Schaffer AA, Klein C (2007) Genetic heterogeneity in severe congenital neutropenia: how many aberrant pathways can kill a neutrophil? Curr Opin Allergy Clin Immunol 7:481–494

    Article  PubMed  Google Scholar 

  7. Welte K, Zeidler C, Dale DC (2006) Severe congenital neutropenia. Semin Hematol 43:189–195

    Article  CAS  PubMed  Google Scholar 

  8. Rosenberg PS, Alter BP Link DC (2007) Neutrophil elastase mutations and risk of leukemia in severe congenital neutropenia. Br J Haematol 140:210–213

    PubMed  Google Scholar 

  9. Rosenberg PS, Alter BP, Bolyard AA et al (2006) Severe Chronic Neutropenia International Registry. The incidence of leukemia and mortality from sepsis in patients with severe CN receivivg long-term G-CSF therapy. Blood 107:4628–4635

    Article  CAS  PubMed  Google Scholar 

  10. Germeshausen M, Ballmaier M, Schulze H et al (2001) Granulocyte colony-stimulating factor receptor mutations in a patient with acute lymphoblastic leukemia secondary to severe CN. Blood 97:829–830

    Article  CAS  PubMed  Google Scholar 

  11. Germeshausen M, Schulze H, Kratz C et al (2005) An acquired G-CSF receptor mutation results in increased proliferation of CMML cells from a patient with severe CN. Leukemia 19:611–617

    CAS  PubMed  Google Scholar 

  12. Germeshausen M, Ballmaier M, Welte K (2007) Incidence of CSF3R mutations in severe CN and relevance for leukemogenesis: results of a long-term survey. Blood 109:93–99

    Article  CAS  PubMed  Google Scholar 

  13. Sloand EM, Yong AS, Ramkissoon S et al (2006) Granulocyte colony-stimulating factor preferentially stimulates proliferation of monosomy 7 cells bearing the isoform IV receptor. Proc Natl Acad Sci USA 103:14483–14488

    Article  CAS  PubMed  Google Scholar 

  14. Zeidler C, Germeshausen M, Klein C, Welre K (2009) Clinical implications of ELA2-, HAX1-, and G-CSF- receptor (CSF3R) mutations in severe congenital neutropenia. Br J of Haematol 144:459–467

    Article  CAS  Google Scholar 

  15. Zeidler C, Welte K, Barak Y et al (2000) Stem cell transplantation in patients with severe CN without evidence of leukemic transformation. Blood 95:1195–1198

    CAS  PubMed  Google Scholar 

  16. Bellanne-Chantelot C, Clauin S, Leblanc T et al (2004) Mutations in the ELA2 gene correlate with more severe expression of neutropenia: a study of 81 patients from the French Neutropenia Register. Blood 103:4119–4125

    Article  CAS  PubMed  Google Scholar 

  17. Rappeport JM, Parkman R, Newburger P et al (1980) Correction of infantile agranulocytosis (Kostmann's syndrome) by allogeneic bone marrow transplantation. Am J Med 68:605–609

    Article  CAS  PubMed  Google Scholar 

  18. Dallorso S, Manzitti C, Dodero P et al (2003) Uneventful outcome of unrelated hematopoietic stem cell transplantation in a patient with leukemic transformation of Kostmann syndrome and long-lasting invasive pulmonary mycosis. Eur J Haematol 70:322–325

    Article  PubMed  Google Scholar 

  19. Toyoda H, Azuma E, Hori H et al (2001) Successful unrelated BMT in a patient with Kostmann syndrome complicated by pre-transplant pulmonary bacterial abscesses. Bone Marrow Transplant 28:413–415

    Article  CAS  PubMed  Google Scholar 

  20. Markel MK, Haut PR, Renbarger JA et al (2008) Unrelated cord blood transplantation for severe congenital neutropenia: report of two cases with very different transplant courses. Pediatr Transplant 12:896–901

    Article  PubMed  Google Scholar 

  21. Ferry C, Ouachee M, Leblanc T et al (2005) Hematopoietic stem cell transplantation in severe congenital neutropenia: experience of the French SCN register. Bone Marrow Transplant 35:45–50

    Article  CAS  PubMed  Google Scholar 

  22. Choi SW, Boxer LA, Pulsipher MA et al (2005) Stem cell transplantation in patients with severe congenital neutropenia with evidence of leukemic transformation. Bone Marrow Transplant 35:473–477

    Article  CAS  PubMed  Google Scholar 

  23. Touw IP, Bontenbal M (2007) Granulocyte colony-stimulating factor: key factor or innocent bystander in the development of secondary myeloid malignancy? JNCI 99:183–186

    CAS  PubMed  Google Scholar 

  24. Etzioni A, Harlan JM (2007) Cell adhesion and leukocyte adhesions defects. In: Smith EM, Puck J, Ochs HD eds. Primary Immune deficiency disease. A molecular and genetic approach, 2nd ed. Oxford University Press 550-564.

  25. Hogg N, Stewart MP, Scarth SL, Newton R, Shaw JM, Law SK et al (1999) A novel leukocyte adhesion deficiency caused by expressed but nonfunctional beta2 integrins MAC-1 and LFA-1. J Clin Invest 103:97–106

    Article  CAS  PubMed  Google Scholar 

  26. Etzioni A, Frydman M, Pollack S, Avidor I, Phillips ML, Paulson JC et al (1992) Brief report: recurrent severe infections caused by a novel leukocyte adhesion deficiency. N Engl J Med 327:1789–1792

    CAS  PubMed  Google Scholar 

  27. Lubke T, Marquardt T, Etzioni A, Hatmann E, von Figura K, Korner C (2001) Complementation cloning identifies CDG-IIc, a new type of congenital disorders of glycosylation, as a GDP-fucose transporter deficiency. Nat Genet 28:73–76

    Article  CAS  PubMed  Google Scholar 

  28. Springer TA (1994) Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 76:301–314

    Article  CAS  PubMed  Google Scholar 

  29. Alon R, Etzioni A (2003) LAD III, a novel group of leukocyte integrin activation deficiencies. Trends Immunol 24:561–566

    Article  CAS  PubMed  Google Scholar 

  30. McDowall A, Inwald D, Leitinger B, Jones A, Liesner R, Klein N et al (2003) A novel form of integrin dysfunction involving beta 1, beta 2 and beta 3 integrins. J Clin Invest 111:51–60

    CAS  PubMed  Google Scholar 

  31. Mory A, Feigelson SW, Yarali N, Kilic SS, Bayhan GI, Gershoni-Baruch R, Etzioni A, Alon R (2008) Kindlin-3: a new gene involved in the pathogenesis of LAD-III. Blood 112:2591

    Article  CAS  PubMed  Google Scholar 

  32. Thomas C, Le Deist F, Cavazzana-Calvo M, Benkerrou M, Haddad E, Blanche S, Hartmann W, Friedrich W, Fischer A (1995) Results of allogeneic bone marrow transplantation in patients with leukocyte adhesion deficiency. Blood 86:1629–1635

    CAS  PubMed  Google Scholar 

  33. Fischer A, Pham HT, Descamps-Latscha B, Grospierre B, Gerota I, Perez N, Scheinmetzler C, Durandy A, Virelizier JL, Griscelli C (1983) Bone marrow transplantation for inborn error of phagocytic cells associated with defective adherence, chemotaxis and oxidative responses during opsonized particle phagocytosis. Lancet 2:473–476

    Article  CAS  PubMed  Google Scholar 

  34. Le Deist F, Blanche S, Keable H, Gaud C, Pham H, Descamps-Latscha B, Wahn V, Griscelli C, Fischer A (1989) Successful HLA non-identical bone marrow transplantation in three patients with the leukocyte adhesion deficiency. Blood 74:512–516

    PubMed  Google Scholar 

  35. Qasim W, Cavazzana-Calvo M, Davies EG, Davis J, Duval M, Eames G et al (2009) Allogeneic hematopoietic stem cell transplantation for leukocyte adhesion deficiency. Pediatrics 123:836–840

    Article  PubMed  Google Scholar 

  36. Mancias C, Infante AJ, Kamani NR (1999) Matched unrelated donor bone marrow transplantation in leukocyte adhesion deficiency. Bone Marrow Transplant 24:1261–1263

    Article  CAS  PubMed  Google Scholar 

  37. Farinha NJ, Duval M, Wagner E, Champagne J, Lapointe N, Barrette S, Tapiero B, Busque L, Champagne MA (2002) Unrelated bone marrow transplantation for leukocyte adhesion deficiency. Bone Marrow Transplant 30:979–981

    Article  CAS  PubMed  Google Scholar 

  38. Engel ME, Hickstein DD, Jr B, Calder C, Manes B, Frangoul H (2006) Matched unrelated bone marrow transplantation with reduced-intensity conditioning for leukocyte adhesion deficiency. Bone Marrow Transplant 37:717–718

    Article  CAS  PubMed  Google Scholar 

  39. Tokunaga M, Miyamura K, Ohashi H, Ishiwada N, Terakura S, Ikeguchi M et al (2007) Successful nonmyeloablative bone marrow transplantation for leukocyte adhesion deficiency type I from an unrelated donor. Int J Hematol 86:91–95

    Article  PubMed  Google Scholar 

  40. Kuijpers TW, van Bruggen R, Kamerbeek N, Tool ATJ, Hicsonmez G, Gurgey A, Karow A, Verhoeven AJ, Seeger K, Sanal O, Niemeyer C, Roos D (2007) Natural history and early diagnosis of LAD-1/variant syndrome. Blood 109:3529–3537

    Article  CAS  PubMed  Google Scholar 

  41. Kuijpers TW, van de Vijver E, Weterman MAJ, de Boer M, Tool ATJ, van den Berg TK, Moser M, Jakobs ME, Seeger K, Sanal O, Unal S, Cetin M, Roos D, Verhoeven AJ, Baas F (2009) LAD-1/variant syndrome is caused by mutations in FERMT3. Blood Dec 8 (in press)

  42. Winkelstein JA, Marino MC, Johnston RB Jr et al (2000) Chronic granulomatous disease. Report on a national registry of 368 patients. Medicine (Baltimore) 79:155–169

    Article  CAS  Google Scholar 

  43. Roos D, van Bruggen R, Meischl C (2003) Oxidative killing of microbes by neutrophils. Microbes and Infection 5:1307–1315

    Article  CAS  PubMed  Google Scholar 

  44. Clark RA, Klebanoff SJ (1979) Chemotactic factor inactivation by the myeloperoxidase-hydrogen peroxide-halide system. J Clin Invest 64:913–920

    Article  CAS  PubMed  Google Scholar 

  45. Seger RA (2008) Modern management of chronic granulomatous disease. British J of Haematology 140:255–266

    Article  CAS  Google Scholar 

  46. Seger RA, Gungor T, Belohradsky BH, Blanche S, Bordigoni P, Di Bartolomeo P, Flood T et al (2002) Treatment of chronic granulomatous disease with myeloablative conditioning and an unmodified hemopoietic allograft: a survey of the European experience, 1985–2000. Blood 100:4344–4350

    Article  CAS  PubMed  Google Scholar 

  47. Schuetz C, Hoenig M, Gatz S, Speth F, Benninghoff U, Schulz A, Debatin KM, Friedrich W (2009) Hematopoietic stem cell transplantation from matched unrelated donors in chronic granulomatous disease. Immunol Res Oct 10 (in press).

  48. Horwitz ME, Barrett AJ, Brown MR, Carter CS, Childs R, Gallin JI, Holland SM, Linton GF, Miller JA et al (2001) Treatment of chronic granulomatous disease with nonmyeloablative conditioning and a T-cell depleted hematopoietic allograft. New England J of Medicine 344:881–888

    Article  CAS  Google Scholar 

  49. Gungor T, Halter J, Klink A, Junge S, Stumpe KD, Seger R, Schanz U (2005) Successful low toxicity hematopoietic stem cell transplantation for high-risk adult chronic granulomatous disease patients. Transplantation 79:1596–1606

    Article  PubMed  Google Scholar 

  50. Dinauer MS, Gifford MA, Pech N, Li II, Emshwiller P (2001) Variable correction of host defense following gene transfer and bone marrow transplantation in murine X-linked chronic granulomatous disease. Blood 97:3738–3745

    Article  CAS  PubMed  Google Scholar 

  51. Stein S, Siler U, Ott MG, Seger R, Grez M (2006) Gene therapy for chronic granulomatous disease. Curr Opin Mol Ther 8:415–422

    CAS  PubMed  Google Scholar 

  52. Malech HL, Maples PB, Whiting-Theobald N, Linton GF, Sekhsaria S et al (1997) Prolong production of NADPH oxidase-corrected granulocytes after gene therapy of chronic granulomatous disease. Proceeding of the National Academy of Sciences of the United States of America 94:12133–12138

    Article  CAS  Google Scholar 

  53. Malech HL, Choi U, Brenner S (2004) Progress toward effective gene therapy for chronic granulomatous disease. Jpn J Infect dis 57:S27–S28

    PubMed  Google Scholar 

  54. Ott MG, Schmidt M, Schwarzwaelder K, Strin S, Siler U, Koehl U, Glimm H, Kuhlcke K et al (2006) Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVII, PRDM16 or SETBP1. Nat Med 12:401–409

    Article  CAS  PubMed  Google Scholar 

  55. Ryser MF, Roesler J, Gentsch M, Brenner S (2007) Gene therapy for chronic granulomatous disease. Expert Opin Biol Ther 7:1799–1809

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ronit Elhasid.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Elhasid, R., Rowe, J.M. Hematopoetic Stem Cell Transplantation in Neutrophil Disorders: Severe Congenital Neutropenia, Leukocyte Adhesion Deficiency and Chronic Granulomatous Disease. Clinic Rev Allerg Immunol 38, 61–67 (2010). https://doi.org/10.1007/s12016-009-8129-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12016-009-8129-y

Keywords

Navigation