Recent advances in stem cell transplantation for Nijmegen breakage syndrome

XIIth meeting of the European Society for Immunodeficiencies, 16-19 October 2008, s’-Hertogenbosch, the Netherlands

What is the Nijmegen breakage syndrome (NBS)?

NBS is a rare auto-somal recessive condition with chromosomal instability. NBS characterized by microcephaly with typical facial appearance (see pictures), growth retardation, immunodeficiency. Chromosomal instability, X-ray hypersensitivity caused very strong predisposition to malignancy. In particular lymphoma and leukemia. A decline in intellectual function with age is observed.

How NBS is diagnosed?

The gene responsible for NBS has been identified on chromosome 8q21. Testing for the 657del5 within exon 6 of the NBS1 gene is available on a clinical basis.

How common is NBS?

NBS seems to be prevalent among Central and Easter European populations. The great majority of NBS patients (~95%) carry a germinal mutation 657del5Is. We found an unexpectedly high carrier frequency of the 657del5 mutation (1/177) in the three Slav populations: Poland, Ukraina and Chech Republik a factor that may contribute to cancer frequency in those countries.

Is there effective treatment for NBS?

Up to now the most effective treatment for NBS is prevention and therapy of cancer and infections. The haematopoetic stem cell transplantation is no routinely considered. The first use of bone marrow transplantation for NBS was reported in 2004. During the XIIIth meeting of European Society for Immunodeficiencies, October 16 – 19, 2008 in ‘s-Hertgenbosch, the Netherlands the lecture ‘Stem cell transplantation for NBS – experience in 5 patients’ was presented by M.H. Albert from Dr. von Haunersches Kinderspital, Department of Infection/Immunity from Munich, Germany.

The NBS children were transplanted in the Great Ormond Street Hospital for Children, London, in the Newcastle General Hospital, and in the Dr. von Haunersches Kinderspital, Munich and in the Zentrum fur Kinder-und Jyngendmedizin in Heidelberg. At a median follow up of 2.6 years (range 1.0 – 6.8) four of five patients are alive and well. The bone marrow transplantation may have a future role for NBS patients.

Ewa Bernatowska MD, PhD,
Professor of Pediatrics and Clinical Immunology Head,
Department of Immunology, The Children's Memorial Health Institute, Poland