Hematopoietic Stem Cell Transplantation for X-Linked Thrombocytopenia With Mutations in the WAS gene.
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.
Clinical Application Department, Center for iPS Cell Research and Application (CiRA), Institute for Integrated Cell-material Sciences, Kyoto University, Kyoto, Japan.
Koichi
K
Oshima
Department of Pediatrics, Tokyo Medical and Dental University (TMDU), 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. kimai.ped@tmd.ac.jp.
Kohsuke
K
Imai
Department of Pediatric Hematology/Oncology, Dr. von Haunersches Children's Hospital, Ludwig-Maximilians-University, Munich, Germany.
Michael H
MH
Albert
Department of Pediatric Hematology/Oncology, Dr. von Haunersches Children's Hospital, Ludwig-Maximilians-University, Munich, Germany.
Tanja C
TC
Bittner
Department of Pediatric Hematology/Oncology, Charite University Medicine, Berlin, Germany.
Gabriele
G
Strauss
Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Alexandra H
AH
Filipovich
Department of Pediatrics, Tokyo Medical and Dental University (TMDU), 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
Tomohiro
T
Morio
Division of Research Immunology and Bone Marrow Transplantation, Children's Hospital of Los Angeles, University of Southern California, Los Angeles, CA, USA.
Neena
N
Kapoor
Department of Pediatric Hematology/Oncology, Children's Mercy Hospital, Kansas City, MO, USA.
Jignesh
J
Dalal
Division of Pediatric Hematology/Oncology/Bone Marrow Transplantation, British Columbia Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada.
Kirk R
KR
Schultz
Division of Hematology/Oncology/Transplant, Children's Hospital of Wisconsin, Wauwatosa, MI, USA.
James T
JT
Casper
Department of Pediatrics, University of Brescia, Brescia, Italy.|The Manton Center for Orphan Disease Research and the Division of Immunology, Children's Hospital, Harvard Medical School, Boston, MA, USA.
Luigi D
LD
Notarangelo
Department of Pediatrics, University of Washington and Seattle Children's Research Institute, Seattle, WA, USA.
Hans D
HD
Ochs
Department of Pediatrics, National Defense Medical College, Saitama, Japan.
Shigeaki
S
Nonoyama
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D018572:Disease-Free Survival; D040181:Genetic Diseases, X-Linked / Q000235:genetics* / Q000401:mortality / Q000628:therapy*; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D009154:Mutation; D012189:Retrospective Studies; D013921:Thrombocytopenia / Q000235:genetics* / Q000401:mortality / Q000628:therapy*; D014923:Wiskott-Aldrich Syndrome / Q000235:genetics; D051316:Wiskott-Aldrich Syndrome Protein / Q000235:genetics*; D055815:Young Adult
C495767:WAS protein, human; D051316:Wiskott-Aldrich Syndrome Protein
Wiskott-Aldrich syndrome; X-linked thrombocytopenia; hematopoietic stem cell transplantation