CD34⁺ Selected T-Cell Depleted Peripheral Blood Stem Cell Transplantation from HLA-Haplocompatible Donors for the Treatment of Severe Combined Immunodeficiency Disease.

We report the results of haplocompatible peripheral blood stem cell transplantation (PBSCT) utilizing CD34⁺ selection and T-cell depletion for 17 patients with severe combined immunodeficiency disease (SCID). Of these patients, 11 had T⁻B⁻NK⁺, 1 had T⁻B⁺NK⁺, and 5 had T⁻B⁺NK⁻ phenotype. A total of 15 cell preparations were processed immediately after collection, in which two were shared between two twin siblings. Total viable nucleated cells (TVNC) in the original cell collections were between 5.9 and 9.13×10¹⁰ (median 7.0×10¹⁰) with 0.47–2.39% (median 0.9%) CD34⁺ cells. After Isolex 300i (Baxter Inc., n=14) or CliniMACS System (Miltenyi Biotec Inc., n=1) processing, a median number of 379×10⁶ (89–970×10⁶) TVNC were recovered, with a median viability of 98% (83–100%) and median purity of 96% (89–100%) CD34⁺ cells. All Isolex processed (n=14) cells were further T-cell depleted with OKT3 monoclonal antibody, yielding a median of 0.09% CD3⁺ cells (0.008–0.4%). One preparation that utilized the CliniMACS System yielded only 0.06% CD3⁺ cells, hence did not receive further T-cell depletion. Recovery of CD34⁺ cells after complete processing was from 13.3% to 60.2% (median 50.1%). Twelve patients (70.6%) are alive 2 months to 8.7 years post transplant. A total of five patients died from infections or transplant-related complications. Four patients suffered from autoimmune hemolytic anemia, which resulted in one death. Fourteen patients engrafted. One of three patients who did not engraft subsequently received a boost from the same donor but eventually died without engraftment, and 2 received a matched unrelated BMT with myeloablative conditioning and recovered T- and B-cell function. At last follow-up the median time for the recovery of T- and B-cell function was 8.5 months and 1 year, respectively. The dose of CD3 did not show any influence on T- or B-cell function recovery (p=0.48 and 0.09, respectively). And the dose of CD34⁺ cells did not influence T-cell function recovery (p=0.1), but did influence B-cell function recovery, which was statistically significant (p=0.02). The B⁻ SCID phenotype is associated with a poorer outcome compared to the B⁺ SCID phenotype, with 50% and 100% survival rates, respectively. However, this result was not statistically significant (p=0.07). Of the 9 surviving patients followed for more than 2 years, most are in good general health. The body height growth curve is within the 5th and 10–25th percentiles in 3 and 4 patients, respectively. For body weight, the growth curve is within 10–25th and 50–75th percentiles in 5 and 2 patients, respectively. Five have achieved successful recovery of both T- and B-cell immunity and require no medication at last visit; however, 2 of these had graft failure following their initial haplocompatible transplant, and received a second BMT from a matched unrelated donor with conditioning. Three patients with X-linked SCID (3/5) didn’t achieve B-cell reconstitution and still require IVIG replacement therapy. Based on these results, we conclude that for SCID patients who lack an HLA-matched related donor, CD34⁺ selected T-cell depleted haplocompatible PBSCT is an effective treatment.