Long-term outcome of non-ablative booster BMT in patients with SCID

Abstract

SCID is a fatal syndrome caused by mutations in at least 13 different genes. It is characterized by the absence of T cells. Immune reconstitution can be achieved through nonablative related donor BMT. However, the first transplant may not provide sufficient immunity. In these cases, booster transplants may be helpful. A prospective/retrospective study was conducted of 49 SCID patients (28.7% of 171 SCIDs transplanted over 30 years) who had received booster transplants to define the long-term outcome, factors contributing to a need for a booster and factors that predicted success. Of the 49 patients, 31 (63%) are alive for up to 28 years. Age at initial transplantation was found to have a significant effect on outcome (mean of 194 days old for patients currently alive, versus a mean of 273 days old for those now deceased, P=0.0401). Persistent viral infection was present in most deceased booster patients. In several patients, the use of two parents as sequential donors resulted in striking T-and B-cell immune reconstitution. A majority of the patients alive today have normal or adequate T-cell function and are healthy. Nonablative booster BMT can be lifesaving for SCID.

Figure 1

The development of T cell function following sequential bone marrow transplants in a girl with CD3 epsilon deficient SCID. Her father was the first donor, but due to the lack of T cell function at 183 days post-transplantation, she received a rigorously T cell-depleted booster transplant from her mother. Following that, she developed some T cell function but chimerism studies revealed that most of the dividing cells were from her father. A third rigorously T cell-depleted transplant was then given from her father and she has subsequently gone on to have excellent long term T cell reconstitution. Subsequent T cell chimerism studies have revealed some chimerism from both parents, with the dominant chimerism being from the father. She does not require IVIG therapy although her B cells are all host.

Figure 2

Development of T cell function in an IL7Rα-Def SCID boy following two rigorously T cell-depleted haploidentical bone marrow transplants. The second one was given after T cell function had failed to develop at 174 days post-transplantation of marrow from his mother. The second transplant was marrow from his father, following which he developed and sustained excellent T cell function. Chimerism studies reveal the T cells to be all paternal. He does not require IVIG therapy although his B cells are all host.

Figure 3

Development of T cell function in another IL7Rα-Def SCID boy following three rigorously T cell depleted haploidentical parental bone marrow transplants. The mother was the donor for the first two, but T cell function failed to develop after either transplant, so a third transplant was given from the father and was subsequently followed by the development of sustained normal T cell function and paternal T cell chimerism.