Inefficient dystrophin expression after cord blood transplantation in Duchenne muscular dystrophy.
We report a boy who received two allogeneic stem cell transplantations from umbilical cord donors to treat chronic granulomatous disease (CGD). The CGD was cured after the second transplantation, but 2.5 years later he was diagnosed with Duchenne muscular dystrophy (DMD). Examinations of his DNA, muscle tissue, and myoblast cultures derived from muscle tissue were performed to determine whether any donor dystrophin was being expressed. The boy was found to have a large-scale deletion on the X chromosome that spanned the loci for CYBB and DMD. The absence of dystrophin led to muscle histology characteristic of DMD. Analysis of myofibers demonstrated no definite donor cell engraftment. This case suggests that umbilical cord-derived hematopoietic stem cell transplantation will not be efficacious in the therapy of DMD without additional interventions that induce engraftment of donor cells in skeletal muscle.
Program in Genomics and Division of Genetics, Children's Hospital Boston and Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
Peter B
PB
Kang
Hart G W
HG
Lidov
Alexander J
AJ
White
Matthew
M
Mitchell
Anuradha
A
Balasubramanian
Elicia
E
Estrella
Richard R
RR
Bennett
Basil T
BT
Darras
Frederic D
FD
Shapiro
Barbara J
BJ
Bambach
Joanne
J
Kurtzberg
Emanuela
E
Gussoni
Louis M
LM
Kunkel
D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000627:therapeutic use; D002648:Child; D002874:Chromosome Mapping; D041321:Chromosomes, Human, X; D003520:Cyclophosphamide / Q000627:therapeutic use; D016189:Dystrophin / Q000172:deficiency* / Q000235:genetics*; D005500:Follow-Up Studies; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006105:Granulomatous Disease, Chronic / Q000235:genetics* / Q000601:surgery*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics* / Q000601:surgery*; D012086:Reoperation; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D016189:Dystrophin; D000074323:Alemtuzumab; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine