Transplantation of T Cell-depleted Marrow from Parents in a Case of Severe Combined Immunodeficiency with Adenosine Deaminase Deficiency

Abstract

A one-month-old boy with severe combined immunodeficiency (SCID) caused by adenosine deaminase (ADA) deficiency was admitted for bone marrow transplantation (BMT). Since the patient had neither sibling nor HLA identical donor, his parents were chosen as donors. Bone marrow cells from the mother were harvested and treated with monoclonal antibodies (CT-2, BA-1, -2 and -3) plus complement for depletion of both T and B lymphocytes. Although 0.5×10⁸ cells per kilogram were transfused, no remarkable reconstitution of immunologic system was observed. Two months later, the second BMT using the frozen cells from the mother was performed but was not successful. At the third and fourth BMTs, bone marrow cells from the father were treated with AET- or neuraminidase-treated SRBCs using a rosetting technique to eliminate T lymphocytes. In addition, a pre-conditioning protocol using cyclophosphamide (CY) was carried out. However, the T cell-depleted bone marrow cells were again rejected. After the third BMT, the responsiveness of the patient's peripheral lymphocytes to PHA was slightly but transiently enhanced. Basal natural killer activity also appeared about this time. This fact might be suggested as one of the reasons of continuous unsuccessful BMTs. The patient finally died of heart failure caused by a toxicity of CY. A very few cases of SCID with ADA deficiency were reported to have been corrected by HLA haploidentical BMT. Further studies regarding pre-conditioning regimens and methods of T cell-depletion are required for successful BMT in this congenital disorder.