Baseline characteristics of patients with ADA-deficient SCID at the time of initial diagnosis
| . | Entire cohort (N = 131) . | Treatment groups . | P . | |||
|---|---|---|---|---|---|---|
| HCT with no preceding ERT (HCT) (N = 56) . | ERT followed by HCT (ERT-HCT) (N = 31) . | ERT followed by gene therapy (ERT-GT) (N = 35) . | ERT only (N = 9) . | |||
| Sex | .802*,† | |||||
| Female | 74 (56.5%) | 29 (51.8%) | 19 (61.3%) | 21 (60.0%) | 5 (55.6%) | |
| Male | 57 (43.5%) | 27 (48.2%) | 12 (38.7%) | 14 (40.0%) | 4 (44.4%) | |
| Age at diagnosis (d) | .040‡ | |||||
| Median (min-max) | 58 (0-4635) | 89 (0-4635) | 82 (0-634) | 26 (0-1157) | 58 (6-316) | |
| Decade of ADA diagnosis | <.001* | |||||
| 1982-1989 | 16 (12.2%) | 13 (23.2%) | 3 (9.7%) | 0 (0.0%) | 0 (0.0%) | |
| 1990-1999 | 30 (22.9%) | 17 (30.4%) | 7 (22.6%) | 4 (11.4%) | 2 (22.2%) | |
| 2000-2009 | 29 (22.1%) | 15 (26.8%) | 8 (25.8%) | 5 (14.3%) | 1 (11.1%) | |
| 2010-2017 | 56 (42.7%) | 11 (19.6%) | 13 (41.9%) | 26 (74.3%) | 6 (66.7%) | |
| PIDTC protocol | .053*,† | |||||
| 6901 | 37 (28.2%) | 10 (17.9%) | 9 (29.0%) | 13 (37.1%) | 5 (55.6%) | |
| 6902 | 94 (71.8%) | 46 (82.1%) | 22 (71.0%) | 22 (62.9%) | 4 (44.4%) | |
| SCID subtype§ | .710*,† | |||||
| Typical SCID | 112 (85.5%) | 48 (85.7%) | 28 (90.3%) | 28 (80.0%) | 8 (88.9%) | |
| Leaky SCID | 19 (14.5%) | 8 (14.3%) | 3 (9.7%) | 7 (20.0%) | 1 (11.1%) | |
| Omenn Syndrome | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | |
| Trigger for diagnosis | .021*,† | |||||
| Family history | 24 (18.9%) | 13 (25.0%) | 5 (16.1%) | 5 (14.3%) | 1 (11.1%) | |
| Infection | 73 (57.5%) | 32 (61.5%) | 21 (67.7%) | 14 (40.0%) | 6 (66.7%) | |
| Newborn screening | 30 (23.6%) | 7 (13.5%) | 5 (16.1%) | 16 (45.7%) | 2 (22.2%) | |
| Missing | 4 | 4 | 0 | 0 | 0 | |
| Infectious status at time of ADA diagnosis | .002*,† | |||||
| Active infection | 52 (41.9%) | 24 (45.3%) | 18 (64.3%) | 5 (14.7%) | 5 (55.6%) | |
| No previous infection | 49 (39.5%) | 17 (32.1%) | 7 (25.0%) | 21 (61.8%) | 4 (44.4%) | |
| Resolved infection | 23 (18.5%) | 12 (22.6%) | 3 (10.7%) | 8 (23.5%) | 0 (0.0%) | |
| Missing | 7 | 3 | 3 | 1 | 0 | |
| Weight percentile for age‖ | .014*,† | |||||
| <5th | 81 (68.1%) | 44 (81.5%) | 18 (66.7%) | 14 (48.3%) | 5 (55.6%) | |
| ≥5th | 38 (31.9%) | 10 (18.5%) | 9 (33.3%) | 15 (51.7%) | 4 (44.4%) | |
| Missing | 12 | 2 | 4 | 6 | 0 | |
| Height percentile for age‖ | .229*,† | |||||
| <5th | 52 (53.1%) | 26 (63.4%) | 11 (45.8%) | 11 (40.7%) | 4 (66.7%) | |
| ≥5th | 46 (46.9%) | 15 (36.6%) | 13 (54.2%) | 16 (59.3%) | 2 (33.3%) | |
| Missing | 33 | 15 | 7 | 8 | 3 | |
| Need for supplemental oxygen‖ | .005*,† | |||||
| No | 86 (72.9%) | 43 (81.1%) | 16 (59.3%) | 24 (82.8%) | 3 (33.3%) | |
| Yes | 32 (27.1%) | 10 (18.9%) | 11 (40.7%) | 5 (17.2%) | 6 (66.7%) | |
| Missing | 13 | 3 | 4 | 6 | 0 | |
| Need for CPAP‖ | .524*,† | |||||
| No | 110 (94.0%) | 50 (96.2%) | 24 (88.9%) | 27 (93.1%) | 9 (100.0%) | |
| Yes | 7 (6.0%) | 2 (3.8%) | 3 (11.1%) | 2 (6.9%) | 0 (0.0%) | |
| Missing | 14 | 4 | 4 | 6 | 0 | |
| Need for mechanical ventilation‖ | .019*,† | |||||
| No | 103 (86.6%) | 49 (87.5%) | 24 (88.9%) | 26 (92.9%) | 4 (50.0%) | |
| Yes | 16 (13.6%) | 7 (12.5%) | 3 (11.1%) | 2 (7.1%) | 4 (50.0%) | |
| Missing | 12 | 0 | 4 | 7 | 1 | |
| Autoimmunity‖ | .831*,† | |||||
| Autoimmune cytopenia | 1 (0.8%) | 0 (0.0%) | 1 (3.2%) | 0 (0.0%) | 0 (0.0%) | |
| None | 124 (96.1%) | 54 (96.4%) | 29 (93.5%) | 32 (97.0%) | 9 (100.0%) | |
| Other | 4 (3.1%) | 2 (3.6%) | 1 (3.2%) | 1 (3.0%) | 0 (0.0%) | |
| Missing | 2 | 0 | 0 | 2 | 0 | |
| Absolute lymphocyte count at diagnosis | .169‡ | |||||
| N with data | 120 | 50 | 31 | 31 | 8 | |
| Median (cells/mm3) (min-max) | 170 (0-2380) | 159 (0-2380) | 170 (0-1220) | 222 (42-999) | 99 (20-400) | |
| CD3+ T-cell count at diagnosis | .152‡ | |||||
| N with data | 115 | 55 | 26 | 27 | 7 | |
| Median (cells/mm3) (min-max) | 26 (0-734) | 26 (0-713) | 14.5 (0-404) | 37 (0-734) | 6 (2-75) | |
| CD4+ T-cell count at diagnosis | .010‡ | |||||
| N with data | 97 | 42 | 24 | 26 | 5 | |
| Median (cells/mm3) (min-max) | 13 (0-346) | 18.9 (0-346) | 8 (0-166) | 26.5 (0-318) | 2 (0-6) | |
| CD8+ T-cell count at diagnosis | .003‡ | |||||
| N with data | 97 | 42 | 24 | 26 | 5 | |
| Median (cells/mm3) (min-max) | 9 (0-501) | 17.5 (0-501) | 4 (0-253) | 9.5 (0-429) | 0 (0-3) | |
| CD19+ (or CD20+) B-cell count at diagnosis | .005‡ | |||||
| N with data | 97 | 38 | 25 | 27 | 7 | |
| Median (cells/mm3) (min-max) | 7 (0-663) | 9 (0-97.3) | 6 (0-122) | 9 (2-663) | 2 (1-5) | |
| CD4+CD45RO+ T-cell count at diagnosis | .112‡ | |||||
| N with data | 29 | 11 | 7 | 9 | 2 | |
| Median (cells/mm3) (min-max) | 11 (0-109) | 35 (0-109) | 5 (0-30) | 25 (4-96) | 2.5 (0-5) | |
| CD4+CD45RA+ T-cell count at diagnosis | .099‡ | |||||
| N with data | 36 | 11 | 9 | 12 | 4 | |
| Median (cells/mm3) (min-max) | 1 (0-63) | 1 (0-63) | 0 (0-4) | 2 (0-35) | 0 (0-0) | |
| CD56+ NK-cell count at diagnosis | .439‡ | |||||
| N with data | 82 | 34 | 18 | 23 | 7 | |
| Median (cells/mm3) (min-max) | 42.5 (0-470) | 41.8 (3-311) | 30.5 (0-194) | 53 (4-470) | 49 (2-174) | |
| Baseline PHA response | .616*,† | |||||
| <10% of LLN | 70 (84.3%) | 41 (85.4%) | 13 (86.7%) | 13 (81.3%) | 3 (75.0%) | |
| 10-30% of LLN | 4 (4.8%) | 1 (2.1%) | 1 (6.7%) | 2 (12.5%) | 0 (0.0%) | |
| >30% of LLN | 9 (10.8%) | 6 (12.5%) | 1 (6.7%) | 1 (6.3%) | 1 (25.0%) | |
| Missing | 48 | 8 | 16 | 19 | 5 | |
| Maternal engraftment of lymphocytes | NA | |||||
| No | 19 | 6 | 7 | 4 | 2 | |
| Missing | 112 | 50 | 24 | 31 | 7 | |
| . | Entire cohort (N = 131) . | Treatment groups . | P . | |||
|---|---|---|---|---|---|---|
| HCT with no preceding ERT (HCT) (N = 56) . | ERT followed by HCT (ERT-HCT) (N = 31) . | ERT followed by gene therapy (ERT-GT) (N = 35) . | ERT only (N = 9) . | |||
| Sex | .802*,† | |||||
| Female | 74 (56.5%) | 29 (51.8%) | 19 (61.3%) | 21 (60.0%) | 5 (55.6%) | |
| Male | 57 (43.5%) | 27 (48.2%) | 12 (38.7%) | 14 (40.0%) | 4 (44.4%) | |
| Age at diagnosis (d) | .040‡ | |||||
| Median (min-max) | 58 (0-4635) | 89 (0-4635) | 82 (0-634) | 26 (0-1157) | 58 (6-316) | |
| Decade of ADA diagnosis | <.001* | |||||
| 1982-1989 | 16 (12.2%) | 13 (23.2%) | 3 (9.7%) | 0 (0.0%) | 0 (0.0%) | |
| 1990-1999 | 30 (22.9%) | 17 (30.4%) | 7 (22.6%) | 4 (11.4%) | 2 (22.2%) | |
| 2000-2009 | 29 (22.1%) | 15 (26.8%) | 8 (25.8%) | 5 (14.3%) | 1 (11.1%) | |
| 2010-2017 | 56 (42.7%) | 11 (19.6%) | 13 (41.9%) | 26 (74.3%) | 6 (66.7%) | |
| PIDTC protocol | .053*,† | |||||
| 6901 | 37 (28.2%) | 10 (17.9%) | 9 (29.0%) | 13 (37.1%) | 5 (55.6%) | |
| 6902 | 94 (71.8%) | 46 (82.1%) | 22 (71.0%) | 22 (62.9%) | 4 (44.4%) | |
| SCID subtype§ | .710*,† | |||||
| Typical SCID | 112 (85.5%) | 48 (85.7%) | 28 (90.3%) | 28 (80.0%) | 8 (88.9%) | |
| Leaky SCID | 19 (14.5%) | 8 (14.3%) | 3 (9.7%) | 7 (20.0%) | 1 (11.1%) | |
| Omenn Syndrome | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | |
| Trigger for diagnosis | .021*,† | |||||
| Family history | 24 (18.9%) | 13 (25.0%) | 5 (16.1%) | 5 (14.3%) | 1 (11.1%) | |
| Infection | 73 (57.5%) | 32 (61.5%) | 21 (67.7%) | 14 (40.0%) | 6 (66.7%) | |
| Newborn screening | 30 (23.6%) | 7 (13.5%) | 5 (16.1%) | 16 (45.7%) | 2 (22.2%) | |
| Missing | 4 | 4 | 0 | 0 | 0 | |
| Infectious status at time of ADA diagnosis | .002*,† | |||||
| Active infection | 52 (41.9%) | 24 (45.3%) | 18 (64.3%) | 5 (14.7%) | 5 (55.6%) | |
| No previous infection | 49 (39.5%) | 17 (32.1%) | 7 (25.0%) | 21 (61.8%) | 4 (44.4%) | |
| Resolved infection | 23 (18.5%) | 12 (22.6%) | 3 (10.7%) | 8 (23.5%) | 0 (0.0%) | |
| Missing | 7 | 3 | 3 | 1 | 0 | |
| Weight percentile for age‖ | .014*,† | |||||
| <5th | 81 (68.1%) | 44 (81.5%) | 18 (66.7%) | 14 (48.3%) | 5 (55.6%) | |
| ≥5th | 38 (31.9%) | 10 (18.5%) | 9 (33.3%) | 15 (51.7%) | 4 (44.4%) | |
| Missing | 12 | 2 | 4 | 6 | 0 | |
| Height percentile for age‖ | .229*,† | |||||
| <5th | 52 (53.1%) | 26 (63.4%) | 11 (45.8%) | 11 (40.7%) | 4 (66.7%) | |
| ≥5th | 46 (46.9%) | 15 (36.6%) | 13 (54.2%) | 16 (59.3%) | 2 (33.3%) | |
| Missing | 33 | 15 | 7 | 8 | 3 | |
| Need for supplemental oxygen‖ | .005*,† | |||||
| No | 86 (72.9%) | 43 (81.1%) | 16 (59.3%) | 24 (82.8%) | 3 (33.3%) | |
| Yes | 32 (27.1%) | 10 (18.9%) | 11 (40.7%) | 5 (17.2%) | 6 (66.7%) | |
| Missing | 13 | 3 | 4 | 6 | 0 | |
| Need for CPAP‖ | .524*,† | |||||
| No | 110 (94.0%) | 50 (96.2%) | 24 (88.9%) | 27 (93.1%) | 9 (100.0%) | |
| Yes | 7 (6.0%) | 2 (3.8%) | 3 (11.1%) | 2 (6.9%) | 0 (0.0%) | |
| Missing | 14 | 4 | 4 | 6 | 0 | |
| Need for mechanical ventilation‖ | .019*,† | |||||
| No | 103 (86.6%) | 49 (87.5%) | 24 (88.9%) | 26 (92.9%) | 4 (50.0%) | |
| Yes | 16 (13.6%) | 7 (12.5%) | 3 (11.1%) | 2 (7.1%) | 4 (50.0%) | |
| Missing | 12 | 0 | 4 | 7 | 1 | |
| Autoimmunity‖ | .831*,† | |||||
| Autoimmune cytopenia | 1 (0.8%) | 0 (0.0%) | 1 (3.2%) | 0 (0.0%) | 0 (0.0%) | |
| None | 124 (96.1%) | 54 (96.4%) | 29 (93.5%) | 32 (97.0%) | 9 (100.0%) | |
| Other | 4 (3.1%) | 2 (3.6%) | 1 (3.2%) | 1 (3.0%) | 0 (0.0%) | |
| Missing | 2 | 0 | 0 | 2 | 0 | |
| Absolute lymphocyte count at diagnosis | .169‡ | |||||
| N with data | 120 | 50 | 31 | 31 | 8 | |
| Median (cells/mm3) (min-max) | 170 (0-2380) | 159 (0-2380) | 170 (0-1220) | 222 (42-999) | 99 (20-400) | |
| CD3+ T-cell count at diagnosis | .152‡ | |||||
| N with data | 115 | 55 | 26 | 27 | 7 | |
| Median (cells/mm3) (min-max) | 26 (0-734) | 26 (0-713) | 14.5 (0-404) | 37 (0-734) | 6 (2-75) | |
| CD4+ T-cell count at diagnosis | .010‡ | |||||
| N with data | 97 | 42 | 24 | 26 | 5 | |
| Median (cells/mm3) (min-max) | 13 (0-346) | 18.9 (0-346) | 8 (0-166) | 26.5 (0-318) | 2 (0-6) | |
| CD8+ T-cell count at diagnosis | .003‡ | |||||
| N with data | 97 | 42 | 24 | 26 | 5 | |
| Median (cells/mm3) (min-max) | 9 (0-501) | 17.5 (0-501) | 4 (0-253) | 9.5 (0-429) | 0 (0-3) | |
| CD19+ (or CD20+) B-cell count at diagnosis | .005‡ | |||||
| N with data | 97 | 38 | 25 | 27 | 7 | |
| Median (cells/mm3) (min-max) | 7 (0-663) | 9 (0-97.3) | 6 (0-122) | 9 (2-663) | 2 (1-5) | |
| CD4+CD45RO+ T-cell count at diagnosis | .112‡ | |||||
| N with data | 29 | 11 | 7 | 9 | 2 | |
| Median (cells/mm3) (min-max) | 11 (0-109) | 35 (0-109) | 5 (0-30) | 25 (4-96) | 2.5 (0-5) | |
| CD4+CD45RA+ T-cell count at diagnosis | .099‡ | |||||
| N with data | 36 | 11 | 9 | 12 | 4 | |
| Median (cells/mm3) (min-max) | 1 (0-63) | 1 (0-63) | 0 (0-4) | 2 (0-35) | 0 (0-0) | |
| CD56+ NK-cell count at diagnosis | .439‡ | |||||
| N with data | 82 | 34 | 18 | 23 | 7 | |
| Median (cells/mm3) (min-max) | 42.5 (0-470) | 41.8 (3-311) | 30.5 (0-194) | 53 (4-470) | 49 (2-174) | |
| Baseline PHA response | .616*,† | |||||
| <10% of LLN | 70 (84.3%) | 41 (85.4%) | 13 (86.7%) | 13 (81.3%) | 3 (75.0%) | |
| 10-30% of LLN | 4 (4.8%) | 1 (2.1%) | 1 (6.7%) | 2 (12.5%) | 0 (0.0%) | |
| >30% of LLN | 9 (10.8%) | 6 (12.5%) | 1 (6.7%) | 1 (6.3%) | 1 (25.0%) | |
| Missing | 48 | 8 | 16 | 19 | 5 | |
| Maternal engraftment of lymphocytes | NA | |||||
| No | 19 | 6 | 7 | 4 | 2 | |
| Missing | 112 | 50 | 24 | 31 | 7 | |
P value reflects comparison between patients receiving ERT only, GT, and HCT with or without pre-HCT ERT.
CPAP, continuous positive airway pressure; EF, ejection fraction; NA, not applicable; SF, shortening fraction.
χ2 test.
Exact test.
Kruskal-Wallis test.
Definition of SCID subtypes used in PIDTC 6901/6902 protocols based on published “Shearer criteria.”57 Typical SCID: CD3+ T cells < 300 cells per cubic millimeter and proliferation to PHA < 10% of the lower limit of normal (except with documented maternal T-cell engraftment) with supporting genetic evidence when available. Leaky SCID: reduced number of CD3+ T cells (≤2 years old: <1000 cells per cubic millimeter; >2 years old and ≤4 years old: <800 cells per cubic millimeter; >4 years old: <600 cells per cubic millimeter) and proliferation to PHA < 30% the lower limit of normal and no maternal T-cell engraftment. Omenn syndrome: Generalized skin rash, no maternal lymphocytes, ≥80% of CD3+ or CD4+ T cells are CD45RO+, with at least 4 of 9 criteria being met including hepatomegaly, splenomegaly, lymphadenopathy, elevated IgE, elevated absolute eosinophil count, oligoclonal T cells, reduced PHA proliferation < 50%, hypomorphic mutation in known SCID gene, and low TRECs and/or CD4+CD31+CD45RA+ and/or CD4+CD45RA+CD62L+ T cells.
Need for supplemental oxygen, CPAP, mechanical ventilation, weight and height percentiles, autoimmunity, and cardiac dysfunction refer to the presence or absence of these features between date of ADA diagnosis and either start of ERT or first definitive cellular therapy (not necessarily whether they were still present at the onset of these treatments).