Background. Children suffering from rare inherited disorders can be cured using stem cell transplantation (SCT). For patients where HLA-identical donor could not be found, there is an excellent chance of identifying a family member who shares an identical haplotype with the patient but whose second haplotype is different. This situation is called an HLA-full haplotype mismatch. Risks of haploidentical transplantation are graft rejection and severe graft-versus-host disease (GVHD). Histocompatibility barriers can be overcome by infusing high doses of T-cell depleted peripheral CD34+ stem cells.
Methods and Results. Between December 1995 and March 2000, 5 children with rare inherited disorders esere transplanted using highly purified CD34+ stem cells from haploidentical parents at the 2nd Department of Pediatrics, University Hospital Motol, Prague. Two children suffered from severe combined immunode%ciency (SCID), one child from malignant osteopetrosis, Wiskott-Aldrich syndom and hemophagocytic lymphohistiocytosis, respectively. Positive selection of peripheral CD34+ stem cells from G-CSF stimulated donors was performed using the method of immunoabsorbtion (Ce11Pro) (n=2) or immunomagnetic separation (C1iniMACS) (n=3). Donor type engraftment was achieved in 4 children. In one of them early graft failure has developed successfully managed by second SCT from the same donor. One child with SCID had primary graft failure. Mild acute GVHD with good response to steroid therapy developed in 2 children. Three children are alive and 2 of them are cured. Two children died due to post-transplant complications - CM V pneumonia and encephalitis.
Conclusions. Transplantation of highly purified CD34+ stem cells from haploidentical parents is a reasonable therapeutic option for children with some speci%c nonmalignant disorders lacking HLA identical donor. Risks of this type of SCT are the graft failure and severe infectious complications due to slovu immunological reconstitution in comparison with SCT from HLA identical donors.
haploidentical transplantation, positive selection of CD34+ cells, T-cell depletion, nonmalignant diseases.