Correction of primary immunodeficiencies with bone marrow transplantation from unrelated donors

Since the establishment of voluntary registries of potential bone marrow donors worldwide, begining in the 1980s, the use of closely-matched unrelated marrow transplantation has gained in popularity and success, especially in the treatment of children with lethal genetic disorders of lymphohematopoeisis and hematologic malignancies who lack histocompatible sibling donors. With the ability to screen more than 3 million HLA- typed donors at a keystroke, it is now possible to identify suitably matched unrelated donors for the majority of children with primary immunodeficiencies in a timeframe that allows safe and effective administration of the unrelated bone marrow. Experience with unrelated donor marrow transplantation in several of the primary immunodeficiencies has shown that, at least in children under five years of age, results with donors mismatched at the A or B locus (but genetically identical at the Dr locus) are as good as those achieved with six antigen matched unrelated donors, and approximate results achieved with matched sibling transplants. The largest numbers of patients with primary immunodeficiencies who have received transplants from unrelated donors to date have had the diagnoses of Wiskott Aldrich syndrome (WAS), Severe Combined Immunodeficiencies (SCID), and Hemophagocytic Lymphohistiocytosis (HLH). In aggregate, patients who have received mostly non-T-depleted unrelated marrow transplants for WAS, SCID, or HLH have experienced an acceptably high rate of donor cell engraftment (> 90%) with initial transplant. Overall survival/cure rates at three years post-translant of > 65% for WAS and SCID, and > 40% for HLH have been documented. Importantly the quality of life of children after unrelated transplant is excellent as rated by the assignment of Karnofsky scores of > 90% in 95% of all survivors.