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.

  • Original Article
  • Published:

Pediatric Transplants

Stem cell transplantation for the Wiskott–Aldrich syndrome: a single-center experience confirms efficacy of matched unrelated donor transplantation

Bone Marrow Transplantation volume 38, pages 671–679 (2006)Cite this article

Abstract

The treatment of Wiskott–Aldrich syndrome (WAS), a once uniformly fatal disorder, has evolved considerably as the use of hematopoietic stem cell transplant has become more widespread. For the majority of patients who lack an human leukocyte antigen-identical sibling, closely matched unrelated donor bone marrow transplant (MUD BMT) at an early age is an excellent option that nevertheless is not uniformly chosen. We retrospectively analyzed our experience with transplantation in 23 patients with WAS from 1990 to 2005 at the University of Brescia, Italy, of whom 16 received MUD BMT. Myeloablative chemotherapy was well tolerated with median neutrophil engraftment at day 18, and no cases of grade III or IV graft-vs-host disease. Overall survival was very good with 78.2% (18/23) of the whole cohort and 81.2% (13/16) of MUD BMT recipients surviving. Among 18 survivors, full donor engraftment was detected in 12 patients, and stable mixed chimerism in all blood lineages in four patients. Deaths were limited to patients who had received mismatched related BMT or who had severe clinical symptomatology at the time of transplantation, further emphasizing the safety and efficacy of MUD BMT when performed early in the clinical course of WAS.

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

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
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Parkman R, Rappeport J, Geha R, Belli J, Cassady R, Levey R et al. Complete correction of the Wiskott–Aldrich syndrome by allogeneic bone-marrow transplantation. N Engl J Med 1978; 298: 921–927.

    Article  CAS  PubMed  Google Scholar 

  2. Brochstein JA, Gillio AP, Ruggiero M, Kernan NA, Emanuel D, Laver J et al. Marrow transplantation from human leukocyte antigen-identical or haploidentical donors for correction of Wiskott–Aldrich syndrome. J Pediatr 1991; 119: 907–912.

    Article  CAS  PubMed  Google Scholar 

  3. Fischer A, Friedrich W, Fasth A, Blanche S, Le Deist F, Girault D et al. Reduction of graft failure by a monoclonal antibody (anti-LFA-1 CD11a) after HLA nonidentical bone marrow transplantation in children with immunodeficiencies, osteopetrosis, and Fanconi's anemia: a European Group for Immunodeficiency/European Group for Bone Marrow Transplantation report. Blood 1991; 77: 249–256.

    CAS  PubMed  Google Scholar 

  4. Filipovich AH, Shapiro RS, Ramsay NK, Kim T, Blazar B, Kersey J et al. Unrelated donor bone marrow transplantation for correction of lethal congenital immunodeficiencies. Blood 1992; 80: 270–276.

    CAS  PubMed  Google Scholar 

  5. Lenarsky C, Weinberg K, Kohn DB, Parkman R . Unrelated donor BMT for Wiskott–Aldrich syndrome. Bone Marrow Transplant 1993; 12: 145–147.

    CAS  PubMed  Google Scholar 

  6. Ozsahin H, Le Deist F, Benkerrou M, Cavazzana-Calvo M, Gomez L, Griscelli C et al. Bone marrow transplantation in 26 patients with Wiskott–Aldrich syndrome from a single center. J Pediatr 1996; 129: 238–244.

    Article  CAS  PubMed  Google Scholar 

  7. Knutsen AP, Steffen M, Wassmer K, Wall DA . Umbilical cord blood transplantation in Wiskott Aldrich syndrome. J Pediatr 2003; 142: 519–523.

    Article  PubMed  Google Scholar 

  8. Filipovich AH, Stone JV, Tomany SC, Ireland M, Kollman C, Pelz CJ et al. Impact of donor type on outcome of bone marrow transplantation for Wiskott–Aldrich syndrome: collaborative study of the International Bone Marrow Transplant Registry and the National Marrow Donor Program. Blood 2001; 97: 1598–1603.

    Article  CAS  PubMed  Google Scholar 

  9. Conley ME, Saragoussi D, Notarangelo L, Etzioni A, Casanova JL . An international study examining therapeutic options used in treatment of Wiskott–Aldrich syndrome. Clin Immunol 2003; 109: 272–277.

    Article  CAS  PubMed  Google Scholar 

  10. Zhu Q, Zhang M, Blaese RM, Derry JM, Junker A, Francke U et al. The Wiskott–Aldrich syndrome and X-linked congenital thrombocytopenia are caused by mutations of the same gene. Blood 1995; 86: 3797–3804.

    CAS  PubMed  Google Scholar 

  11. Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation 1974; 18: 295–304.

    Article  CAS  PubMed  Google Scholar 

  12. Jin Y, Mazza C, Christie JR, Giliani S, Fiorini M, Mella P et al. Mutations of the Wiskott–Aldrich Syndrome Protein (WASP): hotspots, effect on transcription, and translation and phenotype/genotype correlation. Blood 2004; 104: 4010–4019.

    Article  CAS  PubMed  Google Scholar 

  13. Pirovano S, Mazzolari E, Pasic S, Albertini A, Notarangelo LD, Imberti L . Impaired thymic output and restricted T-cell repertoire in two infants with immunodeficiency and early-onset generalized dermatitis. Immunol Lett 2003; 86: 93–97.

    Article  CAS  PubMed  Google Scholar 

  14. Mazzolari E, Moshous D, Forino C, De Martiis D, Offer C, Lanfranchi A et al. Hematopoietic stem cell transplantation in Omenn syndrome: a single center experience. Bone Marrow Transplant 2005; 36: 107–114.

    Article  CAS  PubMed  Google Scholar 

  15. Mullen CA, Anderson KD, Blaese RM . Splenectomy and/or bone marrow transplantation in the management of the Wiskott–Aldrich syndrome: long-term follow-up of 62 cases. Blood 1993; 82: 2961–2966.

    CAS  PubMed  Google Scholar 

  16. Keever CA, Small TN, Flomenberg N, Heller G, Pekle K, Black P et al. Immune reconstitution following bone marrow transplantation: comparison of recipients of T-cell depleted marrow with recipients of conventional marrow grafts. Blood 1989; 73: 1340–1350.

    CAS  PubMed  Google Scholar 

  17. Kook H, Goldman F, Padley D, Giller R, Rumelhart S, Holida M et al. Reconstruction of the immune system after unrelated or partially matched T-cell-depleted bone marrow transplantation in children: immunophenotypic analysis and factors affecting the speed of recovery. Blood 1996; 88: 1089–1097.

    CAS  PubMed  Google Scholar 

  18. Yamaguchi K, Ariga T, Yamada M, Nelson DL, Kobayashi R, Kobayashi C et al. Mixed chimera status of 12 patients with Wiskott–Aldrich syndrome (WAS) after hematopoietic stem cell transplantation: evaluation by flow cytometric analysis of intracellular WAS protein expression. Blood 2002; 100: 1208–1214.

    Article  CAS  PubMed  Google Scholar 

  19. Konno A, Wada T, Schurman SH, Garabedian EK, Kirby M, Anderson SM et al. Differential contribution of Wiskott–Aldrich syndrome protein to selective advantage in T- and B-cell lineages. Blood 2004; 103: 676–678.

    Article  CAS  PubMed  Google Scholar 

  20. Klein C, Nguyen D, Liu CH, Mizoguchi A, Bhan AK, Miki H et al. Gene therapy for Wiskott–Aldrich syndrome: rescue of T-cell signaling and amelioration of colitis upon transplantation of retrovirally transduced hematopoietic stem cells in mice. Blood 2003; 101: 2159–2166.

    Article  CAS  PubMed  Google Scholar 

  21. Strom TS, Turner SJ, Andreansky S, Liu H, Doherty PC, Srivastava DK et al. Defects in T-cell-mediated immunity to influenza virus in murine Wiskott–Aldrich syndrome are corrected by oncoretroviral vector-mediated gene transfer into repopulating hematopoietic cells. Blood 2003; 102: 3108–3116.

    Article  CAS  PubMed  Google Scholar 

  22. Charrier S, Stockholm D, Seye K, Opolon P, Taveau M, Gross DA et al. A lentiviral vector encoding the human Wiskott–Aldrich syndrome protein corrects immune and cytoskeletal defects in WASP knockout mice. Gene Therapy 2005; 12: 597–606.

    Article  CAS  PubMed  Google Scholar 

  23. Martin F, Toscano MG, Blundell M, Frecha C, Srivastava GK, Santamaria M et al. Lentiviral vectors transcriptionally targeted to hematopoietic cells by WASP gene proximal promoter sequences. Gene Therapy 2005; 12: 715–723.

    Article  CAS  PubMed  Google Scholar 

  24. Dupre L, Marangoni F, Scaramuzza S, Trifari S, Hernandez RJ, Aiuti A et al. Efficacy of gene therapy for Wiskott–Aldrich syndrome using a WAS promoter/cDNA-containing lentiviral vector and nonlethal irradiation. Hum Gene Ther 2006; 17: 303–313.

    Article  CAS  PubMed  Google Scholar 

  25. Wada T, Jagadeesh GJ, Nelson DL, Candotti F . Retrovirus-mediated WASP gene transfer corrects Wiskott–Aldrich syndrome T-cell dysfunction. Hum Gene Ther 2002; 13: 1039–1046.

    Article  CAS  PubMed  Google Scholar 

  26. Strom TS, Gabbard W, Kelly PF, Cunningham JM, Nienhuis AW . Functional correction of T cells derived from patients with the Wiskott–Aldrich syndrome (WAS) by transduction with an oncoretroviral vector encoding the WAS protein. Gene Therapy 2003; 10: 803–809.

    Article  CAS  PubMed  Google Scholar 

  27. Dupre L, Trifari S, Follenzi A, Marangoni F, Lain de Lera T, Bernad A et al. Lentiviral vector-mediated gene transfer in T cells from Wiskott–Aldrich syndrome patients leads to functional correction. Mol Ther 2004; 10: 903–915.

    Article  CAS  PubMed  Google Scholar 

  28. Snapper SB, Rosen FS, Mizoguchi E, Cohen P, Khan W, Liu CH et al. Wiskott–Aldrich syndrome protein-deficient mice reveal a role for WASP in T but not B cell activation. Immunity 1998; 9: 81–91.

    Article  CAS  PubMed  Google Scholar 

  29. Wengler GS, Notarangelo LD, Berardelli S, Pollonni G, Mella P, Fasth A et al. High prevalence of nonsense, frame shift, and splice-site mutations in 16 patients with full-blown Wiskott–Aldrich syndrome. Blood 1995; 86: 3648–3654.

    CAS  PubMed  Google Scholar 

  30. Facchetti F, Blanzuoli L, Vermi W, Notarangelo LD, Giliani S, Fiorini M et al. Defective actin polymerization in EBV-transformed B-cell lines from patients with the Wiskott–Aldrich syndrome. J Pathol 1998; 185: 99–107.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was partially contributed by Ministero dell’Istruzione, dell’Università e della Ricerca (MIUR-PRIN 2004), and by the European Union (EURO-POLICY-PID Grant, SP23-CT-2005-006411).

Author information

Authors and Affiliations

  1. Department of Pediatric Hematology-Oncology, Dana-Farber Cancer Institute and Children's Hospital, Boston, MA, USA

    S-Y Pai

  2. Harvard Medical School, Boston, MA, USA

    S-Y Pai

  3. Department of Pediatrics and ‘Angelo Novicelli’ Institute for Molecular Medicine, University of Brescia, Brescia, Italy

    D DeMartiis, C Forino, S Cavagnini, A Lanfranchi, S Giliani, D Moratto, C Mazza, F Porta, L D Notarangelo & E Mazzolari

  4. Terzo Servizio Analisi Chimico-Cliniche, Spedali Civili, Brescia, Italy

    L Imberti

Authors
  1. S-Y Pai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D DeMartiis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C Forino
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S Cavagnini
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A Lanfranchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S Giliani
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. D Moratto
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. C Mazza
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. F Porta
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. L Imberti
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. L D Notarangelo
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. E Mazzolari
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to L D Notarangelo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pai, SY., DeMartiis, D., Forino, C. et al. Stem cell transplantation for the Wiskott–Aldrich syndrome: a single-center experience confirms efficacy of matched unrelated donor transplantation. Bone Marrow Transplant 38, 671–679 (2006). https://doi.org/10.1038/sj.bmt.1705512

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1705512

Keywords

This article is cited by

Search

Advanced search

Quick links