Stem Cell Transplantation in Primary Immunodeficiencies
Purpose of review: To review indications and outcomes of haematopoietic stem cell transplantation in primary immunodeficiencies, in light of recent advances in the field.
Recent findings: Remarkable improvements in the outcome of haematopoietic stem cell transplantation in primary immunodeficiencies have recently been reported. This is a result of the successful use of alternative donors and more effective strategies to prevent and treat complications. These advances have now permitted the indications for haematopoietic stem cell transplantation to be extended in primary immunodeficiencies.
Summary: The optimal results of haematopoietic stem cell transplantation in primary immunodeficiencies have long been obtained with related human leukocyte antigen-identical donors, an option limited to a minority of patients. Transplantation from mismatched related donors has been used with good results mainly in infants with severe combined immune deficiency, but has been associated with significantly delayed or incomplete immune reconstitution. Recent data indicate that transplantation from matched unrelated donors and cord blood transplantation represent valid alternatives, which can be used in all forms of severe primary immunodeficiencies. This, along with careful monitoring of infections, coupled with preemptive treatment, has resulted in a significant improvement in the outcome of haematopoietic stem cell transplantation for severe forms of primary immunodeficiencies.

Haematopoietic stem cell transplantation (HSCT) was shown to cure severe forms of primary immunodeficiencies as early as 1968, but for many years its successful use was largely restricted to human leukocyte antigen (HLA)-identical transplants, because HSCT from mismatched related donors (MMRDs) led to severe complications and graft-versus-host disease (GVHD) in particular.

Different methods (soybean lectin agglutination, depletion with monoclonal antibodies) have been used to attain T-cell depletion from the graft, and thus to prevent GVHD. In the past decade, the positive selection of haematopoietic progenitor cells (identified as CD34-positive cells) has become widely used. This approach removes immature CD34-negative cells and other cells (especially stromal marrow cells) that may facilitate stem cells engraftment. More recently, after the recognition that CD133 is expressed on primitive haematopoietic progenitors, positive selection of CD133-positive cells with immunomagnetic beads has entered into clinical practice.

Regardless of the strategy used, T-cell reconstitution after MMRD-HSCT may take 3-6 months. As a result of this delayed immune reconstitution, infections remain a major cause of morbidity and mortality after MMRD-HSCT for severe combined immunodeficiency (SCID). Furthermore, the long-term outcome after mismatched HSCT for severe primary immunodeficiencies other than SCID remains uncertain. For these reasons, during recent years, many groups have worked at alternative strategies for HSCT in primary immunodeficiencies (Figure 1). This review will concentrate on these developments, with a special focus on new concepts and achievements registered in the past year.



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Cumulative survival after haematopoietic stem cell transplantation for severe forms of primary immunodeficiencies, using different types of donors. Data pertain to experience on 148 children with severe forms of primary immunodeficiencies, transplanted at the authors´ institution in the period 1990–2005. HSCT = Haematopoietic stem cell transplantation; MRD = matched related donor; MMRD = mismatched-related donor; MUD = matched unrelated donor.