Transplantation for severe combined immunodeficiency with HLA-A,B,D,DR incompatible parental marrow cells fractionated by soybean agglutinin and sheep red blood cells

Abstract

Three patients with severe combined immunodeficiency (SCID) received transplants of HLA haplotype-mismatched parental bone marrow depleted of T lymphocytes by differential agglutination with soybean agglutinin (SBA) and subsequent E-rosette depletion. Two patients achieved durable engraftment with reconstitution of both humoral and cell-mediated immunity. Neither of these patients developed graft versus host disease (GVHD). The third patient achieved only a transient engraftment with concomitant development of mitogen-responsive lymphocytes of paternal origin. Our experience indicates that depletion of T lymphocytes by this technique can abrogate the potential of histoincompatible marrow grafts to induce lethal GVHD without limiting immunologic reconstitution. It also provides further evidence of nonimmune mechanisms of graft resistance that may necessitate preparative treatment of patients with SCID before transplantation with HLA- mismatched marrow cells.

How do I perform hematopoietic progenitor cell selection?

“…Early ex vivo attempts to T‐cell deplete marrow before administration used soybean agglutinin and sheep red blood cell rosetting performed on marrow grafts in pediatric patients with immunodeficiency syndromes . Although the methods were basic, they nevertheless resulted in approximately 2.0 logs of T‐cell depletion of the cell graft.…”

The evolution of T‐cell depletion in haploidentical stem‐cell transplantation

“…The first TCD in humans was performed in severe combined immune deficiency (SCID) patients who received haploidentical BM that was depleted of T‐cells using T‐cell selective agglutination with the Soybean lectin (SBA), followed by E‐rosetting with sheep red blood cells. The remaining SBA‐E‐cell fraction afforded depletion of over a thousand‐fold (<5 × 10 4 T‐cells/kg)(Reisner et al , , ), defining the extent of depletion required for preventing GvHD.…”

“…Differences in the expression of SBA receptor in humans required adaptation of this protocol, utilizing differential agglutination as a first step, to deplete T, B and late myeloid cells, while sparing colony–forming units (CFU) and early myeloid cells. To deplete the residual T‐cell subpopulations that escaped agglutination, sedimentation of T lymphocytes forming spontaneous rosettes with sheep red cells, was added as a second step, resulting in a thousand‐fold depletion of T‐cells (Reisner et al , , ; O'Reilly et al , ). The first successful allogeneic TCD transplantation following this protocol was performed in 1980 on a 10‐month‐old female with acute leukaemia, who recovered swiftly and displayed donor‐type cells without GvHD symptoms, in the absence of GvHD prophylaxis (Reisner et al , ).…”

“…In parallel, this technique proved successful in facilitating engraftment of 3‐loci‐mismatched haploidentical transplantation in SCID patients, also in the absence of GvHD. Since the first report of these achievements in 1983 (Reisner et al , ), this method has been successfully used for the treatment of hundreds of SCID patients in multiple centres worldwide (Buckley, ; Hagin & Reisner, ; Pai et al , ) with low mortality. Thus, retrospective analysis of SCID patients shows long‐term survival in 91% of infants, of any age, that were not actively infected at the time of transplantation and that did not require conditioning for engraftment.…”

Allogeneic haemopoietic stem cell transplantation in children: what alternative donor should we choose when no matched sibling is available?

“…Haplo‐identical family donor HSCT has been successfully used since the early 1980s (Reisner et al , 1983), with overall survival rates of 42–89% reported (Table IV) (Buckley et al , 1993; Stephan et al , 1993b; Vossen et al , 1993; Dickinson et al , 1997; Lanfranchi et al , 2000). HFDs are immediately available for nearly all patients and transplantation within the neonatal period has been associated with a 95% overall survival rate (Myers et al , 2002).…”