EVIDENCE FOR ENGRAFTMENT OF DONOR-TYPE MULTIPOTENT CD34(-LYMPHOCYTE RECONSTITUTION AFTER BONE-MARROW TRANSPLANTATION FOR B-SCID() CELLS IN A PATIENT WITH SELECTIVE T)

Severe combined immunodeficiencies (SCID), a heterogeneous group of di sorders of infancy, are fatal without treatment directed at immunologi c reconstitution. Allogeneic bone marrow transplantation (BMT), which is such a treatment presents some unique features in SCID, especially when T-lymphocyte-depleted HLA haploidentical allografts are used. Don or-type T lymphopoiesis, less often B lymphopoiesis, develops, whereas myelopoiesis remains the recipient-type. Little is known about the en grafting cells in this peculiar lymphohematopoietic chimerism and the pathophysiology of the frequent failure of B-lymphocyte reconstitution . To address these issues, we purified CD34(+) BM cells from a patient with selective T-lymphocyte reconstitution after HLA haploidentical B MT for B-SCID. Phenotypic analysis of CD34(+) cells was performed by f low cytometry, and functional studies of donor- and recipient-type CD3 4(+) cells were performed in vitro. Donor-type CD34(+) cells, constitu ting similar to 2% if the CD34(+) cells, were detected; both CD34(+)HL A-DR(-) cells and CD34(+) cells coexpressing B-(CD10 and CD19) and T-( CD2 and CD7) lymphocyte-associated cells surface molecules. Donor-type CD34(+) cells coexpressing myeloid-associated molecules (CD13, CD14, CD15, and CD33) were undetectable. However, donor-type CD34(+) myeloid progenitors could be shown in functional assays. Recipient-type CD34( +) cells coexpressing B- and T-lymphocyte- as well as myeloid-associat ed molecules were detected, but recipient-type CD34(+) cells could not be driven into T-lymphocyte differentiation in vitro. These findings provide evidence for engraftment of multipotent stem cells in our pati ent with B-SCID. Furthermore, the failure of B-lymphocyte reconstituti on cannot be explained by lack of donor-type B-lymphocyte progenitors. Donor-type B lymphopoiesis and myelopoiesis are prevented by an unide ntified mechanism. (C) 1994 by The American Society of Hematology.