Haploidentical Bone Marrow Transplantation in Primary Immune Deficiency: Stem Cell Selection and Manipulation

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T cell depleted stem cell transplantation

Stem cell transplantation offers a curative treatment for many patients with a severe form of immune deficiency, as well as malignant and nonmalignant hematologic disorders. As an identical, related, stem cell donor is available only in a small minority of cases (15%–20%),7 alternative donors are needed. The 2 alternative options are allogeneic stem cell transplantation from an unrelated identical donor and haploidentical related donor (in which the donor and recipient share only 1 of 2

Methods of TCD

Three major TCD methods have been used successfully for the treatment of PID patients.

Long-term survival after TCD HSCT

A review of the literature regarding the long-term results of T cell depleted stem cell transplantation reveals an unexpected variability in the outcome and survival of patients treated. Some of the disparity could result from the nature of the primary disease but other variables should be considered, such as supportive care, the degree of TCD, pretreatment conditioning regimen (CR) and posttransplantation prophylaxis.

GVHD and TCD HSCT

TCD was developed as a method to prevent GVHD when using haploidentical stem cell grafts. The prevention of GVHD is of great importance as retrospective analysis has shown it is a significant risk factor for reduced survival when appearing either in the early form of aGVHD or when present 6 months after transplantation in the form of cGVHD.37, 40

In addition, as was recently suggested, GVHD might impair thymic function and affect long-term T cell immune reconstitution.47, 48 Despite the initial

Engraftment

In the first series of TCD HSCT in SCID patients the problem of early graft rejection, which could be corrected by a second transplant from the other parent, was observed. In the initial work of Reisner and colleagues20 from 1983, all 3 patients who underwent TCD HSCT required repeat stem cell grafts as a result of early graft rejection. Several subsequent studies in which the rate of early graft rejection reached up to 30% and necessitated repeated transplantation confirmed these results.2, 38

Methods to enhance recovery following TCD HSCT

The delayed T cell reconstitution following TCD HSCT is a major clinical problem as it is a period of profound immune deficiency during which the patient is exposed to lethal infectious complication. Several modalities have been suggested in an attempt to shorten the period of risk.

Haploidentical TCD HSCT in the neonatal period improved overall survival rate (95%) and might shorten the period between HSCT and normal T cell function.42 Early CD34+ stem cell boost as a means to correct incomplete

Summary

Several primary immune deficiency diseases can be cured by allogeneic HSCT. In the more severe form of otherwise lethal SCID disease, with the exception of experimental gene therapy, HSCT is the only curative treatment. It is well established that HSCT from an identical related donor offers the best survival outcome, lowest GVHD rate, and to some extent improved immune reconstitution. However, as a matched sibling donor is available for only a few patients, and because SCID is a medical

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    A version of this article was previously published in the Immunology and Allergy Clinics of North America, 30:1.

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