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:

Long-term survival after allogeneic-matched sibling PBSC transplantation with conditioning consisting of low-dose busilvex and fludarabine in a 3-year-old boy with ataxia-telangiectasia syndrome and ALL

Bone Marrow Transplantation volume 48, pages 740–741 (2013)Cite this article

Subjects

Ataxia-telangiectasia (A-T) is an autosomal-recessive chromosomal breakage syndrome caused by the mutations of the ATM gene located on chromosome 11q23. A-T manifests in early childhood with progressive cerebellar ataxia and oculocutaneous telangiectases and is associated with an increased risk of lymphoid malignancies, especially non-Hodgkin’s lymphoma and T-ALL. The incidence of the disease is estimated at 1 in 100 000 live births.1 Heterozygous carriers of ATM mutations have an increased risk of all types of cancers.2 ATM gene targets include P53 and BRCA1, which explains the predisposition of carriers to breast cancer. The chemotherapy tolerance in A-T patients is decreased because of chromosomal instability, but clinical data are scarce.3, 4 For the first time, we report the long-term survival of a 3-year-old boy with A-T syndrome and T-ALL after allogeneic-matched sibling donor PBSC transplantation.

The patient was misdiagnosed at infancy with ataxic cerebral palsy; A-T was confirmed by mutational analysis after a leukaemia diagnosis at the age of 3. Upon presentation, the peripheral blood (PB) count revealed hyperleucocytosis (WBC 66 K/μL) with 67% leukaemic blasts in the PB smear and 71% in the BM. In the flow-cytometric analysis, the blasts were positive for CD5, CD7, CD8, CD10, CD45 and cytoplasmic CD3. The diagnostic karyotyping revealed a complex karyotype with typical del(6q), t(7;14) as well as atypical unbalanced aberrations with three copies of the AML1 gene and deletion of TP53, as highlighted by the following:

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

Relevant articles

Open Access articles citing this article.

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

Figure 1

References

  1. Swift M, Morrell D, Cromartie E, Chamberlin AR, Skolnick MH, Bishop DT . The incidence and gene frequency of ataxia-telangiectasia in the United States. Am J Hum Genet 1986; 39: 573–583.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Swift M, Morrell D, Massey RB, Chase CL . Incidence of cancer in 161 families affected by ataxia-telangiectasia. N Engl J Med 1991; 325: 1831–1836.

    Article  CAS  Google Scholar 

  3. Seidemann K, Henze G, Beck JD, Sauerbrey A, Kühl J, Mann G et al. Non-Hodgkin's lymphoma in pediatric patients with chromosomal breakage syndromes (AT and NBS): experience from the BFM trials. Ann Oncol 2000; 11 (Suppl 1): 141–145.

    Article  Google Scholar 

  4. Bienemann K, Burkhardt B, Modlich S, Meyer U, Möricke A, Bienemann K et al. Promising therapy results for lymphoid malignancies in children with chromosomal breakage syndromes (ataxia teleangiectasia or Nijmegen-breakage syndrome): a retrospective survey. Br J Haematol 2011; 155: 468–476.

    Article  CAS  Google Scholar 

  5. Broccoletti T, Del Giudice E, Cirillo E, Vigliano I, Giardino G, Ginocchio VM et al. Efficacy of very-low-dose betamethasone on neurological symptoms in ataxia-telangiectasia. Eur J Neurol 2011; 18: 564–570.

    Article  CAS  Google Scholar 

  6. EBMT/ESID guidelines for hematopoieic stem cell transplantation for primary immunodeficiencies. 2011, http://www.esid.org/downloads/BMT_Guidelines_2011.pdf.

  7. Ghosh S, Schuster FR, Binder V, Niehues T, Baldus SE, Seiffert P et al. Fatal outcome despite full lympho-hematopoietic reconstitution after allogeneic stem cell transplantation in atypical ataxia telangiectasia. J Clin Immunol 2012; 32: 438–440.

    Article  Google Scholar 

  8. Albert MH, Gennery AR, Greil J, Cale CM, Kalwak K, Kondratenko I et al. Successful SCT for Nijmegen breakage syndrome. Bone Marrow Transplant 2010; 45: 622–626.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Dr Thilo Dörk-Bousset from the Hannover Medical School for providing help with A-T diagnostics.

Author Contribution: Design, data analysis and manuscript writing were performed by MU and KK. Data collection was done by JM. Drafting and critical revision of the paper were performed by JM, ED and OH. Genetic analysis was carried out by ED and OH.

Author information

Authors and Affiliations

  1. Department of Pediatric Bone Marrow Transplantation, Hematology and Oncology, Wrocław Medical University, Wrocław, Poland

    M Ussowicz, J Musiał & K Kałwak

  2. Department of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Wrocław Medical University, Wrocław, Poland

    E Duszeńko & O Haus

  3. Department of Clinical Genetics, Nicolaus Copernicus University in Torun, Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland

    O Haus

Authors
  1. M Ussowicz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J Musiał
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E Duszeńko
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. O Haus
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. K Kałwak
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M Ussowicz.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ussowicz, M., Musiał, J., Duszeńko, E. et al. Long-term survival after allogeneic-matched sibling PBSC transplantation with conditioning consisting of low-dose busilvex and fludarabine in a 3-year-old boy with ataxia-telangiectasia syndrome and ALL. Bone Marrow Transplant 48, 740–741 (2013). https://doi.org/10.1038/bmt.2012.207

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2012.207

This article is cited by

Search

Advanced search

Quick links