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Successful HLA-identical bone marrow transplantation in a patient with PNP deficiency using busulfan and fludarabine for conditioning

Abstract

PNP deficiency is an autosomal recessive metabolic disorder characterized by severe combined immunodeficiency and by complex neurological symptomatology including ataxia, developmental delay and spasticity. Patients usually die in the first or second decade of life due to recurrent infections. The only curative treatment is bone marrow transplantation (BMT). We describe a 22-month-old girl who underwent BMT from her HLA-identical brother. Conditioning consisted of busulfan and fludarabine only, resulting in low toxicity and prompt engraftment. At 18 months after BMT, the girl has developed normal immunological functions, and her neurological status has improved. Bone Marrow Transplantation (2001) 28, 93–96.

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References

  1. Markert ML . Purine nucleoside phosphorylase deficiency Immunodefic Rev 1991 3: 45–81

    CAS  PubMed  Google Scholar 

  2. Simmonds HA . Diagnosis and treatment of inborn errors of purine and pyrimidine metabolism: an overview Adv Exp Med Biol 1994 370: 1–6

    CAS  PubMed  Google Scholar 

  3. Hirschhorn R . Inherited enzyme deficiencies and immunodeficiency: adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) deficiencies Clin Immunol Immunopathol 1986 40: 157–165

    Article  CAS  Google Scholar 

  4. Giblett ER . ADA and PNP deficiencies: how it all began Ann N Y Acad Sci 1985 451: 1–8

    Article  CAS  Google Scholar 

  5. Simmonds HA, Duley JA, Fairbanks LD, McBride MB . When to investigate for purine and pyrimidine disorders. Introduction and review of clinical and laboratory indications J Inherit Metab Dis 1997 20: 214–226

    Article  CAS  Google Scholar 

  6. Gangi-Peterson L, Sorscher DH et al. Nucleotide pool imbalance and adenosine deaminase deficiency induce alterations of N-region insertions during V(D)J recombination J Clin Invest 1999 103: 833–841

    Article  CAS  Google Scholar 

  7. Pannicke U, Tuchschmid P, Friedrich W et al. Two novel missense and frameshift mutations in exons 5 and 6 of the purine nucleoside phosphorylase (PNP) gene in a severe combined immunodeficiency (SCID) patient Hum Genet 1996 98: 706–709

    Article  CAS  Google Scholar 

  8. Aust MR, Andrews LG, Barrett MJ et al. Molecular analysis of mutations in a patient with purine nucleoside phosphorylase deficiency Am J Hum Genet 1992 51: 763–772

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Andrews LG, Markert ML . Exon skipping in purine nucleoside phosphorylase mRNA processing leading to severe immunodeficiency J Biol Chem 1992 267: 7834–7838

    CAS  PubMed  Google Scholar 

  10. Sasaki Y, Iseki M, Yamaguchi S et al. Direct evidence of autosomal recessive inheritance of Arg24 to termination codon in purine nucleoside phosphorylase gene in a family with a severe combined immunodeficiency patient Hum Genet 1998 103: 81–85

    Article  CAS  Google Scholar 

  11. Ortin M, Rhymes H, Weightman H, Darbyshire PJ . Unrelated-donor bone marrow transplantation in the treatment of purine nucleoside phosphorylase deficiency Bone Marrow Transplant 2000 25: (Suppl. 1) 112

    Google Scholar 

  12. Hallett RJ, Gaspar B, Duley JA et al. Allogeneic bone marrow transplantation corrects the immunodeficiency in PNP deficiency but does not reverse the neurological abnormalities Cell Mol Biol Lett 1999 4: 374

    Google Scholar 

  13. Carpenter PA, Ziegler JB, Vowels MR . Late diagnosis and correction of purine nucleoside phosphorylase deficiency with allogeneic bone marrow transplantation Bone Marrow Transplant 1996 17: 121–124

    CAS  PubMed  Google Scholar 

  14. Seidemann K, Tiemann M, Henze G et al. Therapy for non-Hodgkin lymphoma in children with primary immunodeficiency: analysis of 19 patients from the BFM trials Med Pediatr Oncol 1999 33: 536–544

    Article  CAS  Google Scholar 

  15. Nelson DM, Butters KA, Markert ML et al. Correction of proliferative responses in purine nucleoside phosphorylase (PNP)-deficient T lymphocytes by retroviral-mediated PNP gene transfer and expression J Immunol 1995 15: 3006–3014

    Google Scholar 

  16. Wolff JA, Friedmann T . Approaches to gene therapy in disorders of purine metabolism Rheum Dis Clin North Am 1988 14: 459–477

    CAS  PubMed  Google Scholar 

  17. Hassan M, Ljungman P, Ringden O et al. The effect of busulphan on the pharmacokinetics of cyclophosphamide and its 4-hydroxy metabolite: time interval influence on therapeutic efficacy and therapy-related toxicity Bone Marrow Transplant 2000 25: 915–924

    Article  CAS  Google Scholar 

  18. Kapelushnik J, Or R, Slavin S, Nagler A . A fludarabine-based protocol for bone marrow transplantation in Fanconi's anemia Bone Marrow Transplant 1997 20: 1109–1110

    Article  CAS  Google Scholar 

  19. Slavin S, Nagler A, Naparstek E et al. Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases Blood 1998 91: 756–763

    CAS  Google Scholar 

Download references

Acknowledgements

HAS is indebted to EC grant BMH4-CT98–3079.

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Classen, C., Schulz, A., Sigl-Kraetzig, M. et al. Successful HLA-identical bone marrow transplantation in a patient with PNP deficiency using busulfan and fludarabine for conditioning. Bone Marrow Transplant 28, 93–96 (2001). https://doi.org/10.1038/sj.bmt.1703100

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  • DOI: https://doi.org/10.1038/sj.bmt.1703100

Keywords

  • purine nucleoside phosphorylase deficiency
  • SCID
  • bone marrow transplantation
  • fludarabine

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