Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter to the Editor
  • Published:

Remission of Crohn’s disease after cord blood transplantation for leukocyte adhesion deficiency type 1

Bone Marrow Transplantation volume 48, pages 1006–1007 (2013)Cite this article

Subjects

Leukocyte adhesion deficiency type-1 (LAD-1) is a rare autosomal recessive inherited immunodeficiency disorder caused by mutation in the ITGB2 gene (21q22.3), encoding the β2-integrin CD18. β2-integrin glycoprotein complex is required for adhesion dependent functions, such as aggregation, chemotaxis, phagocytosis, cell mediated killing and adherence to vascular endothelium. Patients with LAD-1 develop recurrent bacterial infections beginning in early childhood. In the absence of effective gene therapy, allogeneic hematopoietic SCT is the only therapy, which has been shown to be curative in patients with a severe phenotype. Hematopoietic stem cell transplant (HSCT) for LAD-1 has been reported mostly in children but some adults have been treated using this modality.1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 European experience with HSCT for LAD-1 has been described by Qasim et al.2 who also described use of cord blood transplant (CBT) for LAD-1 in pediatric patients. Reduced intensity conditioning was found to be safe and effective. Mixed donor chimerism achieved was sufficient to prevent significant infections. The therapy, however, is limited due to shortage of HLA matched adult donors. We successfully treated an adult with LAD-1 using non-myeloablative CBT. CBT also led to remission of concurrent Crohn’s disease.

The patient is a 22-year-old male with LAD-1 diagnosed at 3 weeks of age when he presented with a peri-rectal abscess. He had marked leukocytosis at 46 × 109/L and his granulocytes had reduced expression of CD11b, CD11a and CD18 supporting a diagnosis of LAD-1. His childhood was remarkable for over 100 hospitalizations for recurrent severe skin and soft tissue infections requiring i.v. antibiotics and occasionally minor surgeries for drainage of abscesses. At age 13, he was diagnosed with Crohn’s disease, which was confirmed by histology. His requirement for immunosuppressive medications and need for central venous catheters gave rise to further complications including life-threatening bacteremia, mediastinitis and recurrent ulcerative esophageal candidiasis. He also developed two episodes of upper limb venous thrombosis secondary to central venous catheters. He required two ileal resections for stricture formation and bowel obstruction. For the past four years, his LAD-1 has been managed with daily s.c. granulocyte colony stimulating factor injections, resulting in an improvement in the number of severe infections requiring hospitalization and i.v. antibiotics to about 4–5 times a year.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Al-Dhekri H, Al-Mousa H, Ayas M, Al-Muhsen S, Al-Ghonaium A, Al-Ghanam G et al. Allogeneic hematopoietic stem cell transplantation in leukocyte adhesion deficiency type 1: a single center experience. Biol Blood Marrow Transplant 2011; 17: 1245–1249.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  4. Yoshimoto A, Hashii Y, Kashiwagi H, Koizumi M, Tokimasa S, Fujisaki H et al. Successful allogeneic stem cell transplant for leukocyte adhesion deficiency using an adjusted busulfan-containing regimen. Pediatr Transplant 2007; 11: 453–455.

    Article  CAS  PubMed  Google Scholar 

  5. Takahashi D, Nagatoshi Y, Saito Y, Inagaki J, Nagayama J, Shinkoda Y et al. Unrelated bone marrow transplantation using a reduced intensity-conditioning regimen in leukocyte adhesion deficiency. Bone Marrow Transplant 2006; 37: 807–808.

    Article  CAS  PubMed  Google Scholar 

  6. Farinha NJ, Duva M, Wagner E, Champagne J, Lapointe N, Barrette S et al. Unrelated bone marrow transplantation for leukocyte adhesion deficiency. Bone Marrow Transplant 2002; 30: 979–981.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  8. Starý J, Bartůnková J, Kobylka P, Vávra V, Hrusák O, Calda P et al. Successful HLA-identical sibling cord blood transplantation in a 6-year-old boy with leukocyte adhesion deficiency syndrome. Bone Marrow Transplant 1996; 18: 249–252.

    PubMed  Google Scholar 

  9. Thomas C, Le Deist F, Cavazzana-Calvo M, Benkerrou M, Haddad E, Blanche S et al. Results of allogeneic bone marrow transplantation in patients with leukocyte adhesion deficiency. Blood 1995; 86: 1629–1635.

    CAS  PubMed  Google Scholar 

  10. LeDiest F, Blanche S, Keable H, Gaud C, Pham H, Descamp-Latscha B et al. Successful HLA non-identical bone marrow transplantation in three patients with leukocyte adhesion deficiency. Blood 1989; 74: 512–518.

    Google Scholar 

  11. Hamidieh AA, Pourpak Z, Hosseinzadeh M, Fazlollahi MR, Alimoghaddam K, Movahedi M et al. Reduced-intensity conditioning hematopoietic SCT for pediatric patients with LAD-1: clinical efficacy and importance of chimerism. Bone Marrow Transplant 2012; 47: 646–650.

    Article  CAS  PubMed  Google Scholar 

  12. Burt RK, Craig RM, Milanetti F, Quigley K, Gozdziak P, Bucha J et al. Autologous nonmyeloablative hematopoietic stem cell transplantation in patients with severe anti-TNF refractory Crohn’s disease: long-term follow-up. Blood 2010; 116: 6123–6132.

    Article  CAS  PubMed  Google Scholar 

  13. Hasselblatt P, Drognitz K, Potthoff K, Bertz H, Kruis W, Schmidt C et al. Remission of refractory Crohn’s disease by high-dose cyclophosphamide and autologous peripheral blood stem cell transplantation. Aliment Pharmacol Ther 2012; 36: 725–735.

    Article  CAS  PubMed  Google Scholar 

  14. Hommes DW, Duijvestein M, Zelinkova Z, Stokkers PC, Ley MH, Stoker J et al. Long-term follow-up of autologous hematopoietic stem cell transplantation for severe refractory Crohn’s disease. J Crohns Colitis 2011; 5: 543–549.

    Article  PubMed  Google Scholar 

  15. Anumakonda V, Hayee B, Chung-Faye G . Remission and relapse of Crohn’s disease following autologous haematopoietic stem cell transplantation for non-Hodgkin’s lymphoma. Gut 2007; 56: 1325.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Immunotherapy, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA

    S Jain, P Gozdziak, A Morgan & R K Burt

Authors
  1. S Jain
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P Gozdziak
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A Morgan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R K Burt
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S Jain.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jain, S., Gozdziak, P., Morgan, A. et al. Remission of Crohn’s disease after cord blood transplantation for leukocyte adhesion deficiency type 1. Bone Marrow Transplant 48, 1006–1007 (2013). https://doi.org/10.1038/bmt.2012.274

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2012.274

This article is cited by

Search

Advanced search

Quick links