Treatment-related life-threatening adverse events related to induction therapy*
| . | Life-threatening adverse events† . | Fatal adverse events . | ||||
|---|---|---|---|---|---|---|
| . | DXM‡ . | PDN‡ . | P . | DXM‡ . | PDN‡ . | P . |
| N (%§) . | N (%§) . | N (%§) . | N (%§) . | |||
| All patients | 1770 | 1946 | 1770 | 1946 | ||
| All life-threatening events | 124 (7.0) | 53 (2.7) | <.0001 | 42 (2.4) | 19 (1.0) | .0011 |
| Infection-related | 80 (4.5) | 33 (1.7) | <.0001 | 29 (1.6) | 13 (0.6) | .0075 |
| Bacterial¶ | 33 | 16 | 10 | 6 | ||
| Fungal‖ | 29 | 11 | 8 | 3 | ||
| Viral | 4 | 3 | 0 | 3 | ||
| Organism nk/nd | 14 | 3 | 11 | 1 | ||
| Not infection-related | 44 (2.5) | 20 (1.0) | .0009 | 13 (0.7) | 6 (0.4) | .11 |
| Neurologic# | 14 | 5 | 4 | 1 | ||
| Gastrointestinal** | 12 | 4 | 3 | 0 | ||
| Liver | 2 | 0 | 2 | 0 | ||
| Pancreatitis | 2 | 3 | 0 | 1 | ||
| Thrombosis including SVT | 8 | 3 | 2 | 1 | ||
| Other | 6 | 5 | 2 | 3 | ||
| Age <10 y | 1458 | 1593 | 1458 | 1593 | ||
| All life-threatening events | 84 (5.8) | 32 (2.0) | <.0001 | 24 (1.6) | 8 (0.5) | .002 |
| Infection-related | 56 (3.8) | 22 (1.4) | <.0001 | 16 (1.1) | 6 (0.4) | .030 |
| Bacterial | 20 | 12 | 5 | 4 | ||
| Fungal | 22 | 6 | 4 | 0 | ||
| Viral | 4 | 2 | 0 | 2 | ||
| Organism nk/nd | 10 | 2 | 7 | 0 | ||
| Not infection-related | 28 (1.9) | 10 (0.6) | .0016 | 8 (0.5) | 2 (0.1) | .056 |
| Neurologic | 12 | 4 | 3 | 1 | ||
| Gastrointestinal | 5 | 3 | 1 | 0 | ||
| Liver | 2 | 0 | 2 | 0 | ||
| Pancreatitis | 1 | 0 | 0 | 0 | ||
| Thrombosis including SVT | 4 | 0 | 2 | 0 | ||
| Other | 4 | 3 | 0 | 1 | ||
| Age ≥10 y | 312 | 353 | 312 | 353 | ||
| All life-threatening events | 40 (12.8) | 21 (5.9) | .0028 | 18 (5.8) | 11 (3.1) | .13 |
| Infection-related | 24 (7.7) | 11 (3.1) | .0091 | 13 (4.2) | 7 (2.0) | .11 |
| Bacterial | 13 | 4 | 5 | 2 | ||
| Fungal | 7 | 5 | 4 | 3 | ||
| Viral | 0 | 1 | 0 | 1 | ||
| Organism nk/nd | 4 | 1 | 4 | 1 | ||
| Not infection-related | 16 (5.1) | 10 (2.8) | .16 | 5 (1.6) | 4 (1.1) | .74 |
| Neurological | 2 | 1 | 1 | 0 | ||
| Gastrointestinal | 7 | 1 | 2 | 0 | ||
| Liver | 0 | 0 | 0 | 0 | ||
| Pancreatitis | 1 | 3 | 0 | 1 | ||
| Thrombosis including SVT | 4 | 3 | 0 | 1 | ||
| Other | 2 | 2 | 2 | 2 | ||
| . | Life-threatening adverse events† . | Fatal adverse events . | ||||
|---|---|---|---|---|---|---|
| . | DXM‡ . | PDN‡ . | P . | DXM‡ . | PDN‡ . | P . |
| N (%§) . | N (%§) . | N (%§) . | N (%§) . | |||
| All patients | 1770 | 1946 | 1770 | 1946 | ||
| All life-threatening events | 124 (7.0) | 53 (2.7) | <.0001 | 42 (2.4) | 19 (1.0) | .0011 |
| Infection-related | 80 (4.5) | 33 (1.7) | <.0001 | 29 (1.6) | 13 (0.6) | .0075 |
| Bacterial¶ | 33 | 16 | 10 | 6 | ||
| Fungal‖ | 29 | 11 | 8 | 3 | ||
| Viral | 4 | 3 | 0 | 3 | ||
| Organism nk/nd | 14 | 3 | 11 | 1 | ||
| Not infection-related | 44 (2.5) | 20 (1.0) | .0009 | 13 (0.7) | 6 (0.4) | .11 |
| Neurologic# | 14 | 5 | 4 | 1 | ||
| Gastrointestinal** | 12 | 4 | 3 | 0 | ||
| Liver | 2 | 0 | 2 | 0 | ||
| Pancreatitis | 2 | 3 | 0 | 1 | ||
| Thrombosis including SVT | 8 | 3 | 2 | 1 | ||
| Other | 6 | 5 | 2 | 3 | ||
| Age <10 y | 1458 | 1593 | 1458 | 1593 | ||
| All life-threatening events | 84 (5.8) | 32 (2.0) | <.0001 | 24 (1.6) | 8 (0.5) | .002 |
| Infection-related | 56 (3.8) | 22 (1.4) | <.0001 | 16 (1.1) | 6 (0.4) | .030 |
| Bacterial | 20 | 12 | 5 | 4 | ||
| Fungal | 22 | 6 | 4 | 0 | ||
| Viral | 4 | 2 | 0 | 2 | ||
| Organism nk/nd | 10 | 2 | 7 | 0 | ||
| Not infection-related | 28 (1.9) | 10 (0.6) | .0016 | 8 (0.5) | 2 (0.1) | .056 |
| Neurologic | 12 | 4 | 3 | 1 | ||
| Gastrointestinal | 5 | 3 | 1 | 0 | ||
| Liver | 2 | 0 | 2 | 0 | ||
| Pancreatitis | 1 | 0 | 0 | 0 | ||
| Thrombosis including SVT | 4 | 0 | 2 | 0 | ||
| Other | 4 | 3 | 0 | 1 | ||
| Age ≥10 y | 312 | 353 | 312 | 353 | ||
| All life-threatening events | 40 (12.8) | 21 (5.9) | .0028 | 18 (5.8) | 11 (3.1) | .13 |
| Infection-related | 24 (7.7) | 11 (3.1) | .0091 | 13 (4.2) | 7 (2.0) | .11 |
| Bacterial | 13 | 4 | 5 | 2 | ||
| Fungal | 7 | 5 | 4 | 3 | ||
| Viral | 0 | 1 | 0 | 1 | ||
| Organism nk/nd | 4 | 1 | 4 | 1 | ||
| Not infection-related | 16 (5.1) | 10 (2.8) | .16 | 5 (1.6) | 4 (1.1) | .74 |
| Neurological | 2 | 1 | 1 | 0 | ||
| Gastrointestinal | 7 | 1 | 2 | 0 | ||
| Liver | 0 | 0 | 0 | 0 | ||
| Pancreatitis | 1 | 3 | 0 | 1 | ||
| Thrombosis including SVT | 4 | 3 | 0 | 1 | ||
| Other | 2 | 2 | 2 | 2 | ||
DXM, dexamethasone therapy in induction phase Protocol IA; nd, no data; nk, not known; PDN, prednisone therapy in Protocol IA9,10 ; SVT, sinus venous thrombosis.
The table includes all life-threatening events that were related to therapy and occurred during or after induction Protocol IA before start of consolidation element Protocol IB.
An adverse event was considered as life-threatening if its occurrence placed the patient at immediate risk of death. An adverse event that might have caused death, if it had occurred in a more severe form, was not considered as life-threatening.
Randomization group as treated in induction.
Percentages are related to the total number of randomized patients treated in the respective arm.
DXM: gram-negative rods, n = 22 (9 patients died); gram-positive rods, n = 5 (1 patient died); gram-positive coccals, n = 9 (1 patient died). PDN: gram-negative rods, n = 9 (4 patients died); gram-positive rods, n = 3 (1 patient died); gram-positive coccals, n = 4 (1 patient died).
Fungal infections were according to the EORTC/MSG criteria.18 DXM: molds, n = 17 (7 patients died); yeasts, n = 4 (1 patient died); fungus not identified/no data, n = 8 (1 patient died). PDN: molds, n = 3 (2 patients died); yeasts, n = 6 (1 patient died), fungus not identified/no data, n = 2.
DXM: seizure/signs of encephalopathy, n = 7 (1 patient died); cerebral infarction/hemorrhage, n = 6 (3 patients died); severe psychosis, n = 1. PDN: seizure/signs of encephalopathy, n = 3; cerebral infarction/hemorrhage, n = 2 (1 patient died).
DXM: gastrointestinal perforation, n = 6 (1 patient died); gastrointestinal bleeding, n = 5 (1 patient died), necrotizing enterocolitis/esophagitis, n = 1 (died). PDN: gastrointestinal perforation, n = 2, gastrointestinal bleeding, n = 2.