Patient TA (BD: 6/4/95) was diagnosed with SCID at birth by an absent thymic shadow, and low T cells (CD3-110/ul, CD4-2/ul, CD8-7/ul, CD20-1140/ul). A five year old sister, PA, had SCID diagnosed at age 3 months and received two paternal T-depleted haploidentical BMTs at age 8 months and 31 months. At age 5 yrs, PA had normal IgG (1154 mg/dl), IgM (134 mg/dl), IgA (118 mg/dl), CD3 (1490/ul), CD4 (730/ul) and CD8 (730/ul), and is well off all medications. As shown in the Table, sib PA pretransplant was HLA identical to patient TA and posttransplant is a chimera with paternal T and her own B cells.

Table 1
Full size table

The mixed leukocyte culture (MLC) stimulation indices (SI) for LA:TA*(*irradiated) was 29.0, LA:PA* 7.0; PA:TA* 0.6; PA:LA* 0.9; TA:PA* 2.2;TA:LA 4.7*.

Without conditioning, TA received 2.2×109 of sib PA's BM on 7/13/95. TA received IVIG, ganciclovir, trimethoprim-sulfamethoxazole, and cyclosporin posttransplant; no GVH or infection occurred. At age 6 months, immunologic studies show CD4 222/ul, CD8 343/ul, IgG 1437mg/dl, IgM 48 mg/dl, IgA 66 mg/dl, a PHA SI of 17.3 and XX/XY chimerism. MLC between father and patient (LA:TA*) is non-reactive (SI-2.4). This experience confirms that engrafted paternal cells become tolerized to the recipient's HLA antigens following haploidentical BMT and allows these tolerized cells to safely reconstitute the HLA identical sibling of the recipient.