Table 2.
Clinical characteristics of asparaginase-associated toxicities by groups of asparaginase enzyme activity levels
| Asparaginase enzyme activity levels | |||||
|---|---|---|---|---|---|
| Total cohort | Inactivation (0 IU/L) (n = 200) | Measurable AEA (N = 955) | |||
| Events (N = 324) | Low levels (0-99 IU/L) (n = 82) | Therapeutic levels (100-250 IU/L) (n = 543) | High levels (>250 IU/L) (n = 330) | ||
| Allergy | 161 | 149 | 3 | 7 | 2 |
|
Grade* Mild Severe |
36 (22.4%) 125 (77.6%) |
31 (20.8%) 118 (79.2%) |
1 (33.3%) 2 (66.7%) |
4 (57.1%) 3 (42.9%) |
2 (100%) 0 |
| Pancreatitis | 69 | 1 | 4 | 39 | 25 |
| Grade* Mild Severe Unknown |
11 (15.7%) 58 (82.9%) 1 (1.4%) |
1 (100%) 0 0 |
0 4 (100%) 0 |
6 (15%) 33 (85%) 0 |
4 (16%) 20 (80%) 1 (4%) |
| Cysts/pseudocyst in pancreas | 20 (28.6%) | 0 | 1 (25%) | 13 (33%) | 6 (24%) |
| Admission to intensive care unit Intubation Pressure support |
34 (47.9%) 6 (8.5%) 8 (11.3%) |
0 0 0 |
1 (25%) 0 0 |
17 (44%) 1 (2.6%) 2 (5.1%) |
16 (64%) 5 (20%) 6 (24%) |
| Insulin-dependent diabetes mellitus Acute Permanent insulin use |
15 (21.1%) 7 (9.9%) |
0 0 |
0 0 |
12 (31%) 6 (15.4%) |
3 (12%) 1 (4%) |
| Thromboembolism | 43 | 1 | 2 | 31 | 9 |
| Grade* 2a† 2b 3 4 5 |
8 (18.6%) 11 (25.6%) 20 (46.5%) 1 (2.3%) 3 (7.0%) |
0 0 1 (100%) 0 0 |
2 (100%) 0 0 0 0 |
4 (12.9%) 9 (29%) 14 (45.2%) 1 (3.2%) 3 (9.7%) |
2 (22%) 2 (22%) 5 (56%) 0 0 |
| Relation to central venous line | 17 (37.8%) | 0 | 2 (100%) | 10 (32.3%) | 3 (33%) |
| Location Supra-diaphragmatic thromboembolism‡ Infra-diaphragmatic thromboembolism‡ Cerebral sinus venous thrombosis Pulmonary embolism |
17 (37.8%) 10 (22.2%) 15 (33.3%) 3 (6.6%) |
0 0 1 0 |
2 (100%) 0 0 0 |
10 (32.3%) 8 (25.8%) 10 (32.3%) 3 (9.7%) |
3 (33%) 2 (22%) 4 (44%) 0 |
| Osteonecrosis | 51 | 2 | 3 | 28 | 18 |
| Grade* 2-3 3 4 |
27 (52.9%) 2 (3.9%) 22 (43.1%) |
1 (50%) 1 (50%) 0 |
2 (66.7%) 0 1 (33.3%) |
14 (50%) 1 (4%) 13 (46%) |
10 (56%) 0 8 (44%) |
| Number of sites 1 2 3 4 >4 |
28 (54.9%) 15 (29.4%) 3 (5.9%) 4 (7.8%) 1 (1.96%) |
1 (50%) 1 (50%) 0 0 0 |
3(100%) 0 0 0 0 |
16 (57%) 6 (21%) 1 (4%) 4 (14%) 1 (4%) |
8 (44%) 8 (44%) 2 (11%) 0 0 |
*
According to Ponte di Legno Toxicity Working Group consensus definitions.28 Grading is outlined in supplemental Data and supplemental Table 1.
†
Symptomatic thromboembolism related to central venous line. All patients received systemic anticoagulation.
‡
Supra- and infra-diaphragmatic thromboembolism are defined as deep venous thrombosis occurring at any site in the upper and lower venous system, respectively.