Abstract
X-linked thrombocytopenia (XLT) is a mild form of the Wiskott-Aldrich syndrome (WAS) caused by mutations in the WAS gene. A recent retrospective study of the clinical outcome and molecular basis of a large cohort of XLT patients demonstrated that although overall survival is excellent, event free survival is severely affected with conservative treatment. To answer the question whether hematopoietic stem cell transplantation (HSCT) offers a viable alternative therapeutic option in XLT, we retrospectively investigated the outcome of HSCT in a cohort of 24 XLT patients who received HSCT between 1990 and 2011 at 14 transplant centers in the United States, Italy, Germany, Canada, and Japan. The engraftment rate was 100 % and the overall survival rate was 83.3 %. Of the four non-survivors, 2 underwent splenectomy prior to HSCT and died of sepsis, and two of aspergillus infections associated with severe GVHD. In all but one patient, pretransplant complications were resolved by HSCT. Our data indicate that HSCT following myeloablative conditioning is curative and associated with acceptable risks as a treatment option for XLT.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Villa A, Notarangelo L, Macchi P, Mantuano E, Cavagni G, Brugnoni D, et al. X-linked thrombocytopenia and Wiskott-Aldrich syndrome are allelic diseases with mutations in the WASP gene. Nat Genet. 1995;9(4):414–7. doi:10.1038/ng0495-414.
Albert M, Notarangelo L, Ochs H. Clinical spectrum, pathophysiology and treatment of the Wiskott-Aldrich syndrome. Curr Opin Hematol. 2010. doi:10.1097/MOH.0b013e32834114bc.
Kobayashi R, Ariga T, Nonoyama S, Kanegane H, Tsuchiya S, Morio T, et al. Outcome in patients with Wiskott-Aldrich syndrome following stem cell transplantation: an analysis of 57 patients in Japan. Br J Haematol. 2006;135(3):362–6. doi:10.1111/j.1365-2141.2006.06297.x.
Ozsahin H, Cavazzana-Calvo M, Notarangelo L, Schulz A, Thrasher A, Mazzolari E, et al. Long-term outcome following hematopoietic stem-cell transplantation in Wiskott-Aldrich syndrome: collaborative study of the European Society for Immunodeficiencies and European Group for Blood and Marrow Transplantation. Blood. 2008;111(1):439–45. doi:10.1182/blood-2007-03-076679.
Moratto D, Giliani S, Bonfim C, Mazzolari E, Fischer A, Ochs H, et al. Long-term outcome and lineage-specific chimerism in 194 patients with Wiskott-Aldrich syndrome treated by hematopoietic cell transplantation in the period 1980–2009: an international collaborative study. Blood. 2011;118(6):1675–84. doi:10.1182/blood-2010-11-319376.
Albert M, Bittner T, Nonoyama S, Notarangelo L, Burns S, Imai K, et al. X-linked thrombocytopenia (XLT) due to WAS mutations: clinical characteristics, long-term outcome, and treatment options. Blood. 2010;115(16):3231–8. doi:10.1182/blood-2009-09-239087.
Imai K, Morio T, Zhu Y, Jin Y, Itoh S, Kajiwara M, et al. Clinical course of patients with WASP gene mutations. Blood. 2004;103(2):456–64. doi:10.1182/blood-2003-05-1480.
den Dunnen J, Antonarakis S. Nomenclature for the description of human sequence variations. Hum Genet. 2001;109(1):121–4. doi:10.1007/s004390100505.
Jin Y, Mazza C, Christie J, 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(13):4010–9. doi:10.1182/blood-2003-05-1592.
Otsubo K, Kanegane H, Nomura K, Miyawaki T, Ishizawa S. Atypical lymphoproliferative disorder in a patient with X-linked thrombocytopenia. Pediatr Blood Cancer. 2008;51(3):443–4. doi:10.1002/pbc.21644.
Inoue H, Kurosawa H, Nonoyama S, Imai K, Kumazaki H, Matsunaga T, et al. X-linked thrombocytopenia in a girl. Br J Haematol. 2002;118(4):1163–5. doi:10.1046/j.1365-2141.2002.03740.x.
Hoshino A, Shimizu M, Matsukura H, Sakaki-Nakatsubo H, Nomura K, Miyawaki T, et al. Allogeneic bone marrow transplantation appears to ameliorate IgA nephropathy in a patient with X-linked thrombocytopenia. J Clin Immunol. 2014;34(1):53–7. doi:10.1007/s10875-013-9964-4.
Acknowledgments
The authors would like to thank the following Japanese physicians who contributed patient data to this study: H. Kanegane (Toyama); H. Kurosawa (Tochigi); A. Morimoto and T. Imamura (Kyoto); M Inoue (Osaka). This study was supported in part by Japan’s Ministry of Health, Labour and Welfare (to TM, SN), the DeJoria Wiskott-Aldrich Research Fund (to HDO) and by Biotest AG, Dreieich, Germany (to MHA).
Authorship Contributions
K.O. and K.I. collected and analyzed data, and drafted the paper; K.I., H.D.O and S.N. designed and supervised research and revised the manuscript critically for important intellectual content; M.H.A. and L.D.N. submitted data, contributed to the interpretation of data, and revised the manuscript; and T.C.B., G.S., A.H.F., T.M., N.K, J.D., K.R.S., J.T.C. submitted data and contributed to interpretation of data. All authors participated sufficiently in the work to take public responsibility for the content, and gave final approval for publication.
Disclosure of Conflicts of Interest
The authors have no conflict of interest to disclose.
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
Supplementary table 1
(XLSX 12.2 kb)
Rights and permissions
About this article
Cite this article
Oshima, K., Imai, K., Albert, M.H. et al. Hematopoietic Stem Cell Transplantation for X-Linked Thrombocytopenia With Mutations in the WAS gene. J Clin Immunol 35, 15–21 (2015). https://doi.org/10.1007/s10875-014-0105-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10875-014-0105-5