Table 4.
Clinical, genetic, and outcome features of 57 patients with high-risk cytogenetics stratified by clinical risk
| Clinical risk group† | |||
|---|---|---|---|
| Total | Standard/Intermediate | High | |
| Total, n (%) | 57 | 25 | 32 |
| Sex, male (%) | 49% | 48% | 50% |
| Age at relapse, n (%) | |||
| 1‐9 y | 30 (53) | 9 (36) | 21 (66)* |
| 10‐14 y | 14 (25) | 10 (40) | 4 (13) |
| 15‐18 y | 13 (23) | 6 (24) | 7 (23) |
| Genetic subgroup, n (%) | |||
| Haploidy | 5 (9) | 1 (4) | 4 (13)** |
| Low hypodiploidy | 5 (9) | 1 (4) | 4 (13) |
| KMT2A translocation | 23 (40) | 6 (24) | 17 (53) |
| iAMP21 | 19 (33) | 16 (24) | 3 (9) |
| t(17;19) | 3 (5) | 0 (0) | 3 (9) |
| t(9;22) | 2 (4) | 1 (4) | 1 (3) |
| Time to first relapse, n (%)‡ | |||
| Very early | 17 (30) | 0 (0) | 17 (53)*** |
| Early | 23 (40) | 8 (32) | 15 (47) |
| Late | 17 (30) | 17 (68) | 0 (0) |
| Site of first relapse, n (%)§ | |||
| Isolated BM | 42 (74) | 14 (56) | 28 (88)* |
| Isolated CNS | 9 (16) | 6 (24) | 3 (9) |
| Combined | 6 (11) | 5 (20) | 1 (3) |
| MRD, n (%)¶ | |||
| Positive | 18 (62) | 10 (77) | 8 (50) |
| Negative | 11 (38) | 3 (23) | 8 (50) |
| Unknown/not done | 28 | 12 | 16 |
| Stem cell transplant, n (%)‖ | |||
| Yes | 28 (67) | 15 (71) | 13 (62) |
| No | 14 (33) | 6 (29) | 8 (38) |
| Induction drug randomization/allocation, n (%)# | |||
| Mitoxantrone | 30 (63) | 18 (72) | 12 (52) |
| Idarubicin | 18 (38) | 7 (28) | 11 (48) |
| Outcome of induction therapy†† | |||
| Induction failure | 9 (16) | 1 (4) | 8 (25) |
| Induction death | 6 (11) | 3 (12) | 3 (9) |
| Second CR | 42 (74) | 21 (84) | 21 (66) |
| Outcome of patients achieving a second remission | |||
| Relapsed | 18 (43) | 7 (33) | 11 (52) |
| Died in CR | 9 (21) | 5 (24) | 4 (19) |
| Continuing second CR | 15 (36) | 9 (42) | 6 (28) |
| Survival at 5 y, % (95% CI) | |||
| Progression-free | 20% (6‐33) | 25% (8‐46) | 18% (6‐33) |
| Overall | 26% (14‐40) | 29% (9‐52) | 22% (9‐39) |
| Hazard ratio (95% confidence interval), P | |||
| Progression-free | — | 1 | 1.57 (0.84‐2.95), .2 |
| Overall | — | 1 | 1.77 (0.91‐3.42), .09 |
P values from χ2 or log rank tests as appropriate: *P < .05; **P < .01; ***P < .001.
†Patients with very early relapses or early isolated marrow relapses were classified as clinically high risk with all other patients classified as clinical intermediate/standard risk.
Time to first relapse was defined as very early (<18 months after initial diagnosis), early (<6 months after the end of treatment) or late (>6 months after the end of treatment).
Site of relapse was defined as isolated marrow, isolated CNS, or other, which included all combined relapses as well as other isolated extramedullary relapses (eg, testes).
Minimal residual disease (MRD) was evaluated by real‐time qPCR analysis of immunoglobulin and T-cell receptor gene rearrangements on marrow samples obtained at relapse and day 35 of induction, and classified as positive (>0.01%) or negative (<0.01%).
Restricted to the 42 patients who achieved a second CR.
Excluded the 9 high-risk patients who received clofarabine.
Induction failure was defined as ≥5% blasts, persistence of CSF blasts, or nonregression of testicular enlargement by day 35. Patients were defined as having achieved a second complete remission CR if they had <5% blasts in the marrow or no blasts in the CSF at the end of phase 1.