Successful human umbilical cord blood stem cell transplantation without conditioning in severe combined immune deficiency

Abstract

Summary:A 2-month-old girl with severe combined immunodeficiency (SCID), presented with mild staphylococcal skin infection, lymphopenia, low T cell number, absence of B cells, high number of NK cells, and a negligible response to mitogens. Since her older brother died as a result of SCID 2 years earlier, cord blood was harvested from a sister born 2. years earlier, who was normal and fully matched both by serology and molecular typing. In view of her clinical condition and in spite of a high number of NK cells with normal activity, HUCBT without preparative conditioning was performed. No G-CSF was administered. Engraftment with mixed chimerism was evident 3 weeks post transplantation. There were no peritransplantation complications. Eighteen months post transplantation, the girl is in excellent condition, blood counts are normal, T cell engraftment is complete, B cell engraftment is proceeding gradually, and the mitogen stimulation tests are normal. Due to the unique nature of HUCB hematopoietic cells, engraftment without conditioning may be possible in patients with SCID with fully matched donors. This is the first HUCBT performed without conditioning. Keywords: severe combined immunodeficiency (SCID); human umbilical cord blood transplantation (HUCBT); microsatellite sequences; mixed chimerism Severe combined immunodeficiency (SCID) is a heterogenous, lethal, congenital disorder of lymphoid progenitors resulting in the failure of T cells to respond to mitogens and specific antigens, and the inability of B cells to produce specific antibodies. SCID immunophenotypes can be classified according to the presence (B+ SCID) or absence (BϪ SCID) of B cells in the peripheral blood of the patients. 1 There are several causes for the more common B+ SCID

Long-term cultured human umbilical cord neural-like cells transplanted into the striatum of NOD SCID mice

“…The fact that the cells transplanted into the striatum did not survive to 30 days may be due to the absence of this immunosuppressive therapy, suggesting that inhibition of the aspects of immunity remaining in the SCID mouse that can be blocked by immunosuppressive drugs, are crucial in the survival of these transplants. Of interest with respect to this, is the successful treatment of a SCID child with her normal sister's cord blood cells; she still has excellent health 18 months later [40]. Surprisingly, no evidence of an immune response was apparent at either time point in our study.…”

Unrelated cord blood transplantation for severe combined immunodeficiency and other primary immunodeficiencies

“…It is even debatable whether any conditioning regimen at all should be used in PID, since favourable results have been obtained in some cases with no conditioning treatment. 31,32,43 The fact that UCB transplants can be performed with greater tolerance to HLA disparity does not necessarily rule out the development of GvHD grades II-IV, the incidence of which oscillates between 33 and 37%. 17,18,20 Of note, 8 of 15 patients in our series (53%) developed GvHD grades II-IV and 5 of these were III-IV.…”

Successful unrelated cord blood transplantation in two children with severe combined immunodeficiency syndrome

“…A ZAP-70 deficiency patient successfully treated by bone marrow transplantation has recently been reported. 15 Data presented in this report suggest that umbilical cord blood represents an alternative source of hemopoietic stem cells in patients affected by SCID, [6][7][8][9] as both patients had a full and rapid B and T lymphocyte reconstitution after UCBT with normal values and response to mitogens 6 months after transplantation. Furthermore, in spite of the HLA disparity, one of our patients had acute GVHD grade I and the other grade III, but at transplant he presented in an overall poor condition, which may have influenced the onset of GVHD.…”

“…Successful UCBT has now been performed in several SCID patients. [6][7][8][9] No data on UCBT for either type of disease presented in this report are available. A ZAP-70 deficiency patient successfully treated by bone marrow transplantation has recently been reported.…”

“…1 Since 1968, these diseases have been successfully treated by BMT [2][3][4][5] and, in recent years, by umbilical cord blood transplantation (UCBT). [6][7][8][9] In this report, we describe the successful immunological reconstitution, following myeloablative UCBT, in two patients affected by a Zap-70 deficiency and by an Omenn-like syndrome. Zap-70 deficiency is a rare autosomal recessive form of SCID because of mutations within the kinase domain of ZAP-70, which is critical for CD8+ T-cell development.…”