Table 4.
Clinical and laboratory parameters over time for the three patients treated with bortezomib-based regimen (patient 3)
| Patient 3 | ||||
|---|---|---|---|---|
| Baseline | Initial improvement phase | Period of rising anti-rhGAA IgG titers | Immunomodulation with bortezomib-based regimen | |
| Prior to ERT | Week 1 → week 34 of ERT | Week 34 → week 88 of ERT | Week 88 of ERT onward | |
| Anti-rhGAA IgG titers | Seronegative | 1:12,800 → 1:51,200 | 1:51,200 → 1:204,800 | 1:204,800 → 1:3,200 |
| Cardiac status (LVMI (g/m2))a | WNL | WNL | WNL | WNL |
| Urinary Glc4 (mmol/mol creatinine) | 67b | NA | 111b → 149.2b | 149.2 → 66.9b |
| Gross motor status | Delayed gross motor milestones, with inability to ambulate or sit unsupported | Acquired new motor milestones; ability to ride a stationary hand-pedal exercise machine up to 15 min | Less energy and less exercise tolerance than previously noted; able to stay in a stander for 25 min | Improved motor control, including holding himself upright while in a stander; able to stay in stander for up to 3 h |
| Respiratory status | Required continuous ventilatory support | Improvement in ventilator status (ability to spend 1 h daily off ventilator) | Increased requirement for ventilation; remained on synchronized intermittent mandatory ventilation without a backup breath rate for 1 hour; increased need for tracheostomy suction | Decrease in ventilatory requirements with ability to come off of the ventilator for short periods of time; remains on synchronized intermittent mandatory ventilation without a backup breath rate for the whole day; decreased requirement for tracheostomy suction |
| Feeding status | Gastrostomy tube | Gastrostomy tube | Gastrostomy tube | Oral with improvement in swallow function plus supplementary gastrostomy tube feeds |
Baseline: before initiation of ERT.
ERT, enzyme replacement therapy; GAA, glucosidase α; LVMI, left-ventricular mass index; NA, not available; urinary Glc4, urinary glucose tetrasaccharide; WNL, within normal limits.
a
Upper limit of normal LVMI: 65 g/m2 (>2 SD higher than upper limit of the age-appropriate normal mean).
b
Control range for ages >3 years: 3 mmol/mol of creatinine.