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

Access through your institution Buy or subscribe 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. * ATM REACTIVATION REVERSES ATAXIA TELANGIECTASIA PHENOTYPES IN VIVO * Sara Di Siena * , Federica Campolo *  … 

Manuela Pellegrini _Cell Death & Disease_ Open Access 22 February 2018 * ATAXIA TELANGIECTASIA: A REVIEW * Cynthia Rothblum-Oviatt * , Jennifer Wright *  … Howard M. Lederman _Orphanet

Journal of Rare Diseases_ Open Access 25 November 2016 ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 12 print issues and online access $259.00 per year

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checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support REFERENCES * 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  *

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  *

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  * 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  * 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  * EBMT/ESID guidelines for hematopoieic stem cell transplantation for primary immunodeficiencies. 2011,

http://www.esid.org/downloads/BMT_Guidelines_2011.pdf. * 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  * 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 * Department of Pediatric Bone Marrow Transplantation, Hematology and Oncology, Wrocław Medical University, Wrocław, Poland M Ussowicz, J Musiał 

& K Kałwak * Department of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Wrocław Medical University, Wrocław, Poland E Duszeńko & O Haus * Department of Clinical

Genetics, Nicolaus Copernicus University in Torun, Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland O Haus Authors * M Ussowicz View author publications You can also search for this author

inPubMed Google Scholar * J Musiał View author publications You can also search for this author inPubMed Google Scholar * E Duszeńko View author publications You can also search for this

author inPubMed Google Scholar * O Haus View author publications You can also search for this author inPubMed Google Scholar * K Kałwak View author publications You can also search for this

author inPubMed 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: 29 October 2012 * Issue Date: May 2013 * DOI: https://doi.org/10.1038/bmt.2012.207 SHARE THIS ARTICLE Anyone you share the

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