HLA-haploidentical bone marrow transplantation in three infants with adenosine deaminase deficiency: Stable immunological reconstitution and reversal of skeletal abnormalities

Abstract

Three infants with severe combined immunodeficiency and adenosine deaminase (ADA) deficiency were treated by T-cell depleted bone marrow transplantation (BMT), using human leukocyte antigen (HLA)-haploidentical parents as donors. In the first patient, two initial transplants failed to engraft and no change of the immunodeficiency was observed. In order to overcome this graft resistance, cytoreductive conditioning was used prior to a third transplant. In the other two patients, similar conditioning was used prior to initial transplants. In all three patients, complete and permanent immunological reconstitution was observed and they survive from 3.5 to 5 years after transplantation. In biopsies obtained from iliac bones prior to BMT, osteochondral abnormalities characteristic of ADA-deficiency were noted in all three patients. After successful transplantation, these abnormalities had completely resolved. Our results demonstrate that cytoreductive conditioning prior to HLA-haploidentical BMT is useful in order to obtain stable engraftment and reversal of abnormalities associated with ADA deficiency.