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Allogeneic-matched sibling stem cell transplantation in a 13-year-old boy with ataxia telangiectasia and EBV-positive non-Hodgkin lymphoma

Bone Marrow Transplantation volume 51, pages 1271–1274 (2016)Cite this article

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Mutations in the ataxia telangiectasia mutated (ATM) gene cause chromosomal instability leading to ataxia telangiectasia (AT). The AT phenotype classically combines cerebellar ataxia, vermal atrophy, athetosis, ocular motor abnormalities, physical and mental retardation, hypogonadism, and telangiectasia predominantly of the face and eyes. Affected persons commonly suffer from hypogammaglobulinemia and functional T-cell defects and have an increased risk of developing acute leukemias and lymphomas. As a consequence, life expectancy is decreased due to recurrent infections and malignancies.1, 2

We report on a 13-year-old boy with AT who developed EBV-associated lymphoproliferation and was cured by chemotherapy followed by allogeneic stem cell transplantation (HSCT) from his HLA-identical sibling. Until he developed lymphoproliferation, the patient was seen as an outpatient for his known AT caused by compound heterozygosity for two splice site mutations within the ATM gene (IVS38-2A>G in exon 39 and c.6095G>A (R2032K) in exon 43). The patient’s parents were each heterozygous for one of the mutations and the patient’s clinically unaffected brother, who was the bone marrow donor, was heterozygous for IVS38-2A>G. ATM kinase activity was not analyzed before bone marrow transplantation (BMT). However, the main effect of the c.6095G>A (R2032K) mutation is aberrant splicing causing a frameshift mutation and premature termination of transcription. The resulting protein will lack its kinase domain and ATM expression will be low or absent. The ATM kinase activity on the other allele (IVS38A>G) was expected to be low to normal. At this stage, the patient showed mental and growth retardation, and suffered from cellular and humoral immunodeficiency (Table 1), his endocrine system showed prepubertal values with a clinical Tanner stage 1. To our knowledge, this is the first report on a child with AT and non-Hodgkin lymphoma (NHL) surviving after HSCT.

Table 1 Lymphocyte and immunoglobulin values indicating immunodeficiency at the start of treatment for EBV-positive lymphoproliferation, at the time of NHL and before and after allogeneic HSCT
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References

  1. Micol R, Ben Slama L, Suarez F, Le Mignot L, Beaute J, Mahlaoui N et al. Morbidity and mortality from ataxia-telangiectasia are associated with ATM genotype. J Allergy Clin Immunol 2011; 128: 382–389.e1.

    Article  Google Scholar 

  2. Suarez F, Mahlaoui N, Canioni D, Andriamanga C, Dubois d’Enghien C, Brousse N et al. Incidence, presentation, and prognosis of malignancies in ataxia-telangiectasia: a report from the French national registry of primary immune deficiencies. J Clin Oncol 2015; 33: 202–208.

    Article  Google Scholar 

  3. Seidemann K, Henze G, Beck JD, Sauerbrey A, Kuhl 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: 141–145.

    Article  Google Scholar 

  4. Chao MM, Kuehl JS, Strauss G, Hanenberg H, Schindler D, Neitzel H et al. Outcomes of mismatched and unrelated donor hematopoietic stem cell transplantation in Fanconi anemia conditioned with chemotherapy only. Ann Hematol 2015; 94: 1311–1318.

    Article  CAS  Google Scholar 

  5. Ussowicz M, Musial J, Duszenko E, Haus O, Kalwak K . 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 2013; 48: 740–741.

    Article  CAS  Google Scholar 

  6. 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 

  7. Bagley J, Cortes ML, Breakefield XO, Iacomini J . Bone marrow transplantation restores immune system function and prevents lymphoma in Atm-deficient mice. Blood 2004; 104: 572–578.

    Article  CAS  Google Scholar 

  8. Ayas M, Al-Seraihi A, El-Solh H, Al-Ahmari A, Khairy A, Aldali A et al. The Saudi experience in fludarabine-based conditioning regimens in patients with Fanconi anemia undergoing stem cell transplantation: excellent outcome in recipients of matched related stem cells but not in recipients of unrelated cord blood stem cells. Biol Blood Marrow Transplant 2012; 18: 627–632.

    Article  CAS  Google Scholar 

  9. Socie G, Gluckman E, Raynal B, Petit T, Landman J, Devergie A et al. Bone marrow transplantation for Fanconi anemia using low-dose cyclophosphamide/thoracoabdominal irradiation as conditioning regimen: chimerism study by the polymerase chain reaction. Blood 1993; 82: 2249–2256.

    CAS  PubMed  Google Scholar 

  10. 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 

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

    Article  CAS  Google Scholar 

  12. Srisirirojanakorn N, Finegold MJ, Gopalakrishna GS, Klish WJ . Hepatic veno-occlusive disease in ataxia-telangiectasia. J Pediatr 1999; 134: 786–788.

    Article  CAS  Google Scholar 

  13. Sandoval C, Swift M . Treatment of lymphoid malignancies in patients with ataxia-telangiectasia. Med Pediatr Oncol 1998; 31: 491–497.

    Article  CAS  Google Scholar 

  14. Kaymaz NE, Kupeli S, Yalcin B, Buyukpamukcu M . Hemorrhagic cystitis in a child with Hodgkin lymphoma and ataxia-telangiectasia after cyclophosphamide. Pediatr Blood Cancer 2009; 53: 516.

    Article  Google Scholar 

  15. Cohen JM, Cuckow P, Davies EG . Bladder wall telangiectasis causing life-threatening haematuria in ataxia-telangiectasia: a new observation. Acta Paediatr 2008; 97: 667–669.

    Article  Google Scholar 

  16. Christmann M, Heitkamp S, Lambrecht E, Doerries K, Schubert R, Zielen S . Haemorrhagic cystitis and polyomavirus JC infection in ataxia telangiectasia. J Pediatr Urol 2009; 5: 324–326.

    Article  Google Scholar 

  17. Chao MM, Ebell W, Bader P, Beier R, Burkhardt B, Feuchtinger T et al. Consensus of German transplant centers on hematopoietic stem cell transplantation in Fanconi anemia. Klin Padiatr 2015; 227: 157–165.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Hannover Medical School, Pediatric Hematology and Oncology, Hannover, Germany

    R Beier, K-W Sykora, B Maecker-Kolhoff, M Sauer & C Kratz

  2. Justus Liebig University, Pediatric Hematology and Oncology, Giessen, Germany

    W Woessmann

  3. Hannover Medical School, Institute of Pathology, Hannover, Germany

    H H Kreipe

  4. Hannover Medical School, University Women’s Hospital, Hannover, Germany

    T Dörk-Bousset

  5. Department of Pediatrics, University of Lübeck, University Hospital Schleswig-Holstein, Hannover, Germany

    M Lauten

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  1. R Beier
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Correspondence to K-W Sykora.

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Beier, R., Sykora, KW., Woessmann, W. et al. Allogeneic-matched sibling stem cell transplantation in a 13-year-old boy with ataxia telangiectasia and EBV-positive non-Hodgkin lymphoma. Bone Marrow Transplant 51, 1271–1274 (2016). https://doi.org/10.1038/bmt.2016.93

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