Low-intensity hematopoietic stem-cell transplantation across human leucocyte antigen barriers in dyskeratosis congenita.
Since the results of conventional hematopoietic stem-cell transplantation (HSCT) for patients with dyskeratosis congenita (DC) are poor owing to the high incidence of transplant-related complications, we explored the use of a low-intensity HSCT regimen. We report two children with DC with severe cytopenia, who underwent successful HSCT from a matched unrelated donor after conditioning with fludarabine, cyclophosphamide, and antithymocyte globulin. Graft-versus-host-disease (GVHD) prophylaxis consisted of corticosteroids and cyclosporin A. The regimen was well tolerated, no significant transplant-related complications were observed, and engraftment was rapid and complete. At 15 and 16 months after HSCT, the children were fully engrafted, in excellent clinical condition, full-donor chimerism, and no signs of GVHD. We conclude that a low-intensity regimen is sufficient to induce durable engraftment using matched unrelated donor HSCT in DC patients, with minimal 1-year transplant-related toxicity. Longer follow-up will determine whether this regimen also reduces long-term toxicity.
Marrow Failure and Myelodysplasia Programme, Division of Haematology and Oncology, Department of Paediatrics, The Hospital for Sick Children and the University of Toronto, Toronto, Ontario, Canada.
Y
Y
Dror
M H
MH
Freedman
M
M
Leaker
J
J
Verbeek
C A
CA
Armstrong
F E
FE
Saunders
J J
JJ
Doyle
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D002675:Child, Preschool; D016572:Cyclosporine / Q000627:therapeutic use; D019871:Dyskeratosis Congenita / Q000628:therapy*; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control; D006680:HLA Antigens / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D033581:Stem Cell Transplantation / Q000379:methods*
D000305:Adrenal Cortex Hormones; D006680:HLA Antigens; D007166:Immunosuppressive Agents; D016572:Cyclosporine