Table 4. Outcome of those with a CNS relapses in ALL R3 by risk parameters defined at first diagnosis, and at relapse.
| Univariate Analysis | |||||||
| PFS | OS | ||||||
| N | %PFS | %OS | Hazard ratio | p-value | Hazard ratio | p-value | |
| At Original Diagnosis | |||||||
| Presenting WC | |||||||
| WC <50×109/l | 73 | 53·8 (40·2, 65·6) | 46·6 (34·1,58·1) | 1 | 1 | ||
| WC ≥50×109/l | 35 | 42·9 (25·0, 59·6) | 31·6 (16·0–48·3) | 1·37 (0·81, 2·32) | 0·246 | 1·19 (0·67, 2·13) | 0·549 |
| Unknown | 15 | - | - | ||||
| Age at Diagnosis | |||||||
| <10 years | 97 | 54·8 (43·1, 65·1) | 46·0 (34·8, 56·4) | 1 | 1 | ||
| ≥10 years | 26 | 15·5 (2·9, 37·3) | 9·9 (0·9,31·9) | 3·03 (1·79, 5·12) | <0·001 | 2·76 (1·57, 4·87) | <0·001 |
| Early Response | |||||||
| Rapid Early Response | 67 | 47·5 (33·7, 60·0) | 39·6 (27·1, 51·8) | 1 | 1 | ||
| Slow Early Response | 29 | 42·1 (23·5, 59·7) | 35·8 (18·6, 53·4) | 1·40 (0·79, 2·46) | 0·245 | 1·41 (0·77, 2·58) | 0·261 |
| Unknown | 27 | - | - | ||||
| At Relapse | |||||||
| Age at relapse | |||||||
| <10 years | 78 | 48·2 (36·6, 59·8) | 55·4 (42·1, 66·7) | 1 | 1 | ||
| ≥10 years | 45 | 22·9 (10·7, 37·9) | 33·1 (17·9, 49·0) | 2·11 (1·31, 3·40) | 0·002 | 1·94 (1·15, 3·24) | 0·012 |
| Gender | |||||||
| Female | 35 | 44·5 (26·1, 61·4) | 42·3 (23·9, 59·5) | 1 | 1 | ||
| Male | 88 | 36·5 (25·6, 47·6) | 49·1 (36·8, 60·3) | 1·30 (0·75, 2·50) | 0·354 | 0·98 (0·56, 1·72) | 0·94 |
| Immunophenotype | |||||||
| B-cell | 97 | 41·9 (31·1, 52·3) | 51·7 (39·9, 62·2) | 1 | 1 | ||
| T-cell | 26 | 33·9 (16·7, 52·0) | 33·3 (14·8, 53·1) | 1·95 (1·12, 3·41) | 0·019 | 2·09 (1·16, 3·76) | 0·014 |
| Time to Relapse | |||||||
| Late | 32 | 64·0 (44·2, 78·3) | 69·1 (48·7, 82·7) | 1 | 1 | ||
| Early | 71 | 27·1 (15·8, 39·8) | 36·2 (22·9, 49·7) | 2·45 (1·29, 4·70) | 2·56 (1·26, 5·17) | ||
| Very Early | 20 | 32·0 (12·3, 53·8) | 41·9 (19·5, 63·0) | 2·95 (1·34, 6·52) | 0·012 | 2·53 (1·07, 5·98) | 0·029 |
| Site of Relapse | |||||||
| i-CNS | 80 | 38·0 (26·2, 49·7) | 50·8 (37·5, 62·6) | 1 | 1 | ||
| c-CNS | 43 | 40·6 (25·1, 55·6) | 40·9 (24·9, 56·3) | 1·04 (0·634, 1·704) | 0·876 | 1·32 (0·78, 2·22) | 0·304 |
| CNS Blast Count (/µl) | |||||||
| <50 | 42 | 35·9 (20·0, 52·0) | 39·3 (22·4, 55·9) | 1 | 1 | ||
| 50–99 | 13 | - | 16·2 (1·1, 48·1) | 1·59 (0·75, 3·36) | 1·31 (0·57, 2·97) | ||
| ≥100 | 54 | 39·4 (25·1, 53·4) | 52·8 (36·6, 66·7) | 0·93 (0·54, 1·60) | 0·335 | 0·69 (0·38, 1·25) | 0·238 |
| Unknown | 14 | - | - | ||||
| Risk category | |||||||
| Standard | 12 | 64·8 (31·0, 85·2) | 80·2 (40·3, 94·8) | 1 | 1 | ||
| Intermediate | 88 | 41·4 (30·0, 52·3) | 50·5 (38·3, 61·5) | 1·87 (0·67, 5·21) | 3·29 (0·79, 13·63) | ||
| High | 23 | 15·5 (3·0, 37·2) | 11·6 (1·0, 36·9) | 3·99 (1·34, 11·94) | 0·008 | 7·85 (1·79, 34·43) | 0·002 |
| Cytogenetics | |||||||
| progenitor B | |||||||
| Good | 43 | 54.8 (38.1, 68.8) | 63.5 (45.0, 77.3) | 1 | 1 | ||
| Intermediate | 29 | 32.8 (16.0, 50.8) | 41.8 (22.7, 59.9) | 1.71 (0.89,3.27) | 1.96 (0.95, 4.01) | ||
| Poor | 11 | 10.2 (1.0,36.4) | 35.1 (8.4, 64.1) | 4.38 (1.95,9.82) | 3.55 (1.43, 8.82) | ||
| Unknown | 14 | 43.5 (8.3, 75.7) | 43.5 (8.3, 75.7) | 1.21 (0.45,3.25) | 1.95 (0.70, 5.43) | ||
| T-cell | 26 | 33.9 (16.7, 52.0) | 33.3 (14.8, 53.1) | 2.85 (1.46,5.54) | 0.0018 | 3.31 (1.60, 6.84) | 0.0126 |
| Therapy | |||||||
| Idarubicin | 44 | 26·5 (14·4, 40·1) | 35·5 (21·7,49·5) | 1 | 1 | ||
| Mitoxantrone | 79 | 48·9 (36·0, 60·6) | 56·9 (42·9,68·7) | 0·65 (0·40,1·04) | 0·075 | 0·57 (0·34, 0·97) | 0·036 |
Rapid early response = <25% blasts in the marrow aspirate on day 8/15 of induction; Slow early response = ≥25% blasts in the marrow aspirate on day 8/15 of induction.