Clinical and immunological outcome of patients with cartilage hair hypoplasia after hematopoietic stem cell transplantation

  1. Victoria Bordon1,*,
  2. Andrew R Gennery2,
  3. Mary A Slatter2,
  4. Els Vandecruys1,
  5. Genevieve Laureys1,
  6. Paul Veys3,
  7. Waseem Qasim3,
  8. Wilhelm Friedrich4,
  9. Nico M Wulffraat5,
  10. Franziska Scherer6,
  11. Andrew J Cant2,
  12. Alain Fischer7,
  13. Marina Cavazzana-Calvo8,
  14. Robbert GM Bredius9,
  15. Luigi D Notarangelo10,
  16. Evelina Mazzolari11,
  17. Benedicte Neven7, and
  18. Tayfun Güngör6
  1. 1 Pediatric Hematology, Oncology and Stem Cell Transplantation, Kliniek voor Kinderziekten C. Hooft, Ghent University Hospital, Ghent, Belgium;
  2. 2 Newcastle University, Newcastle upon Tyne, United Kingdom;
  3. 3 Departments of Bone Marrow Transplantation and Clinical Immunology, Great Ormond Street Hospital, London, United Kingdom;
  4. 4 Universitatskinderklinik und Poliklinik, Ulm, Germany;
  5. 5 Utrecht University Hospital, Utrecht, Netherlands;
  6. 6 Division of Immunology/Hematology/BMT, University Children's Hospital, Zurich, Switzerland;
  7. 7 Assistance Publique Hopitaux de Paris, Hopital Necker-Enfants Malades, service d'immuno-hematologie pediatrique, Paris, France;
  8. 8 Assistance Publique Hopitaux de Paris, Hopital Necker-Enfants Malades, service de biotherapie, Paris, France;
  9. 9 Department of Pediatrics, Leiden University Medical Center, Leiden, Netherlands;
  10. 10 The Manton Center for Orphan Disease Research and Division of Immunology, Children's Hospital, Boston, MA, United States;
  11. 11 Oncology-Haematology Unit, Clinica Pediatrica, Spedali Civili, Brescia, Italy
  1. * Corresponding author; email: victoria.bordon{at}uzgent.be

Abstract

Cartilage-hair hypoplasia (CHH) is a rare autosomal recessive disease caused by mutations in the RMRP gene. Beside dwarfism, CHH has a wide spectrum of clinical manifestations including variable grades of combined immunodeficiency, autoimmune complications and malignancies. Previous reports in single CHH patients with significant immunodeficiencies have demonstrated that allogeneic hematopoietic stem cell transplantation (HSCT) is an effective treatment for the severe immunodeficiency, while growth failure remains unaffected. Since long-term experience in larger cohorts of CHH patients after HSCT is currently unreported, we performed a European collaborative survey reporting on 16 patients with CHH and immunodeficiency who underwent HSCT. Immune dysregulation, lymphoid malignancy and autoimmunity were important features in this cohort. Thirteen patients were transplanted in early childhood (~2.5 years). The other 3 patients were transplanted at adolescent age. Ten of 16 patients (62.5 %) were long-term survivors, with a median follow-up of 7 years. T-lymphocyte numbers and function have normalized and autoimmunity has resolved in all survivors. HSCT should be considered in CHH patients with severe immunodeficiency/autoimmunity, before the development of severe infections, major organ damage or malignancy might jeopardize the outcome of HSCT and the quality of life in these patients.

  • Submitted January 6, 2010.
  • Accepted March 23, 2010.

This Article

  1. Published online before print April 7, 2010, doi: 10.1182/blood-2010-01-259168 Blood April 7, 2010 blood-2010-01-259168
  1. » Abstract
  2. Full Text (PDF)
  4. Supplemental Appendix
  5. All Versions of this Article:
    1. blood-2010-01-259168v1
    2. 116/1/27 most recent

e-Letters

  1. Submit an e-Letter
  2. No e-Letters published

This Week's Issue

  1. January 26, 2012, 119 (4)
  1. Current Issue
  1. Alert me to new issues of Blood