Table 1 Characteristics of XSCID... | American Society of Hematology

Table 1

Characteristics of XSCID patients and their autologous retrovirally transduced CD34⁺ hematopoietic cells

Patient	P1	P2	P3
Early history
IL2RG mutation	Poly-A addition site	R289X	M145 frame shift
Expression of γc protein at cell surface	Trace amount; functional	Normal amount; nonfunctional truncated	None
Age at first BM transplantation, mo	6	11	6
No. of prior haploidentical parental BM transplantations	4	2	1
Adequate T-cell function for more than 2 y after BM transplantation	No	Yes	Yes
Evaluation prior to gene therapy
Age at gene therapy, y	11	10	14
Weight and height percentile for age*	<3%	<3%	<3%
Chronic conditions in addition to recurrent pneumonias and poor growth	Diarrhea, eczema, asthma, alopecia	Diarrhea, sinusitis, asthma, alopecia, malabsorption	Diarrhea, sinusitis, bronchiectasis, warts
BMT donor chimerism	No donor engraftment	T cells, 49% donor; other lineages, 100% host	T cells, 100% donor; other lineages, 100% host
CD3⁺ T cells/μL, nl 650-2108	91	209	1361
CD4⁺ T cells/μL, nl 362-1275	84	56	168
CD19⁺ B cells/μL, nl 49-424	263	435	14
CD16/56⁺ CD3⁻ NK cells/μL, nl 87-505	9	0	3
Transduction of CD34⁺ cells
Initial CD34⁺ cells/kg placed in culture*	2.77×10⁷	2.33×10⁷	1.79×10⁷
Total cells/kg harvested, 80%-90% CD34⁺†	9.5×10⁷	8.0×10⁷	7.8×10⁷
CD34⁺ γc-transduced cells/kg, final product‡	2.92×10⁷	2.85×10⁷	3.13×10⁷
Retroviral copies/transduced cell, final product§	1.1	2.3	3.7

Patient	P1	P2	P3
Early history
IL2RG mutation	Poly-A addition site	R289X	M145 frame shift
Expression of γc protein at cell surface	Trace amount; functional	Normal amount; nonfunctional truncated	None
Age at first BM transplantation, mo	6	11	6
No. of prior haploidentical parental BM transplantations	4	2	1
Adequate T-cell function for more than 2 y after BM transplantation	No	Yes	Yes
Evaluation prior to gene therapy
Age at gene therapy, y	11	10	14
Weight and height percentile for age*	<3%	<3%	<3%
Chronic conditions in addition to recurrent pneumonias and poor growth	Diarrhea, eczema, asthma, alopecia	Diarrhea, sinusitis, asthma, alopecia, malabsorption	Diarrhea, sinusitis, bronchiectasis, warts
BMT donor chimerism	No donor engraftment	T cells, 49% donor; other lineages, 100% host	T cells, 100% donor; other lineages, 100% host
CD3⁺ T cells/μL, nl 650-2108	91	209	1361
CD4⁺ T cells/μL, nl 362-1275	84	56	168
CD19⁺ B cells/μL, nl 49-424	263	435	14
CD16/56⁺ CD3⁻ NK cells/μL, nl 87-505	9	0	3
Transduction of CD34⁺ cells
Initial CD34⁺ cells/kg placed in culture*	2.77×10⁷	2.33×10⁷	1.79×10⁷
Total cells/kg harvested, 80%-90% CD34⁺†	9.5×10⁷	8.0×10⁷	7.8×10⁷
CD34⁺ γc-transduced cells/kg, final product‡	2.92×10⁷	2.85×10⁷	3.13×10⁷
Retroviral copies/transduced cell, final product§	1.1	2.3	3.7

Patients weights at time of treatment: P1, 23 kg; P2, 21.5 kg; P3, 24.5 kg.

†

Cultured and transduced cells were harvested 96 hours after initiation of culture.

‡

A calculated number based upon total cells infused, where the percent of CD34⁺ cells was determined on the day of infusion but where the percent of total cells expressing high levels of γc⁺ transgene was determined by flow cytometry with anti-CD132 fluorescent antibodies on a portion of the infused transduced cells retained in culture for 3 additional days to allow full expression of γc transgene. In the case of P2, whose cells at baseline expressed truncated, nonfunctional γc, transduced cells were clearly identifiable as a population with significantly increased anti-CD132 fluorescence.

A calculated number based on quantitative real-time DNA PCR using virus-specific primers and probes and on measurement of the percentage of cells expressing γc transgene on a portion of the transduced cells retained in culture for 3 additional days to ensure that only integrated vector contributed to the measured copy number.

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