Treatment and risk stratification differences on AALL1231 vs AALL0434
| . | AALL1231 . | AALL0434 . |
|---|---|---|
| Induction corticosteroid | Dexamethasone | Prednisone |
| 6 mg/m2 per d × 28 d | 60 mg/m2 per d × 28 d | |
| Maintenance corticosteroid | Dexamethasone | Prednisone |
| 6 mg/m2 per d × 5 d each 28-d cycle | 40 mg/m2 per d × 5 d each 28-d cycle | |
| Asparginase | 2 doses of pegaspargase during induction | 1 dose of pegaspargase during induction |
| 3 doses of pegaspargase during DI | 2 doses of pegaspargase during DI | |
| Interim maintenance | C-MTX if SR | Randomized to C-MTX or HD-MTX except |
| HD-MTX and C-MTX if IR | Induction failure or CNS-3 and then HD-MTX | |
| VHR intensification blocks and C-MTX if VHR | ||
| Cranial Radiation T-ALL | CNS-3: 18 Gy during maintenance | CNS-3: 18 Gy during DI |
| VHR: 12 Gy during maintenance | IR/HR C-MTX arm: 12 Gy during consolidation | |
| No radiation for SR/IR CNS-1 or CNS-2 | IR/HR HD-MTX arm: 12 Gy during DI | |
| No radiation for LR | ||
| Cranial Radiation T-LLy | CNS-3: 18 Gy during maintenance | CNS-3 not eligible |
| No radiation for patients with CNS-1 or CNS-2 T-LLy | No radiation for patients with CNS-1 or CNS-2 T-LLy | |
| Randomized questions | ± nelarabine (6, 5-d courses): all patients but LR and induction failure. Induction failure nonrandomly assigned to received nelarabine | |
| ± bortezomib during induction and delayed intensification all patients | C-MTX vs HD-MTX interim maintenance as described above | |
| Risk stratification | ||
| LR | National Cancer Institute SR by age (1.00-9.99 y) and WBC (initial ≤50 000/μL); RER, M1 on d 15 and M1 marrow with MRD <0.1% on d 29; CNS-1 status and no testicular disease at diagnosis | |
| SR | CNS-1, lumbar puncture before steroid therapy (not steroid pretreated), d 29 (end of induction) bone marrow M1, d 29 bone marrow MRD ≤0.01%, no testicular leukemia at diagnosis | |
| CNS-2 and CNS-3 cannot be SR and are assigned to IR or VHR based on marrow response | ||
| IR | Not SR or VHR | RER or SER, M1 marrow with MRD <1% on d 29; any CNS status |
| HR | M2 marrow and/or MRD ≥1% on d 29; any CNS status | |
| VHR | M3 marrow at d 29 and/or end of consolidation MRD ≥0.1% |
| . | AALL1231 . | AALL0434 . |
|---|---|---|
| Induction corticosteroid | Dexamethasone | Prednisone |
| 6 mg/m2 per d × 28 d | 60 mg/m2 per d × 28 d | |
| Maintenance corticosteroid | Dexamethasone | Prednisone |
| 6 mg/m2 per d × 5 d each 28-d cycle | 40 mg/m2 per d × 5 d each 28-d cycle | |
| Asparginase | 2 doses of pegaspargase during induction | 1 dose of pegaspargase during induction |
| 3 doses of pegaspargase during DI | 2 doses of pegaspargase during DI | |
| Interim maintenance | C-MTX if SR | Randomized to C-MTX or HD-MTX except |
| HD-MTX and C-MTX if IR | Induction failure or CNS-3 and then HD-MTX | |
| VHR intensification blocks and C-MTX if VHR | ||
| Cranial Radiation T-ALL | CNS-3: 18 Gy during maintenance | CNS-3: 18 Gy during DI |
| VHR: 12 Gy during maintenance | IR/HR C-MTX arm: 12 Gy during consolidation | |
| No radiation for SR/IR CNS-1 or CNS-2 | IR/HR HD-MTX arm: 12 Gy during DI | |
| No radiation for LR | ||
| Cranial Radiation T-LLy | CNS-3: 18 Gy during maintenance | CNS-3 not eligible |
| No radiation for patients with CNS-1 or CNS-2 T-LLy | No radiation for patients with CNS-1 or CNS-2 T-LLy | |
| Randomized questions | ± nelarabine (6, 5-d courses): all patients but LR and induction failure. Induction failure nonrandomly assigned to received nelarabine | |
| ± bortezomib during induction and delayed intensification all patients | C-MTX vs HD-MTX interim maintenance as described above | |
| Risk stratification | ||
| LR | National Cancer Institute SR by age (1.00-9.99 y) and WBC (initial ≤50 000/μL); RER, M1 on d 15 and M1 marrow with MRD <0.1% on d 29; CNS-1 status and no testicular disease at diagnosis | |
| SR | CNS-1, lumbar puncture before steroid therapy (not steroid pretreated), d 29 (end of induction) bone marrow M1, d 29 bone marrow MRD ≤0.01%, no testicular leukemia at diagnosis | |
| CNS-2 and CNS-3 cannot be SR and are assigned to IR or VHR based on marrow response | ||
| IR | Not SR or VHR | RER or SER, M1 marrow with MRD <1% on d 29; any CNS status |
| HR | M2 marrow and/or MRD ≥1% on d 29; any CNS status | |
| VHR | M3 marrow at d 29 and/or end of consolidation MRD ≥0.1% |
Other components of therapy, including type and doses of anthracyclines and alkylating agents were the same in both trials. Supplemental Table 2 provides a detailed description of AALL1231 therapy; the same doses and schedules were used in AALL0434 except those noted in Table 1.
RER: M1 marrow on either day 8 or 15, and M1 marrow with MRD <0.1% on day 29.
SER: M2 or M3 marrow on day 15 or positive MRD ≥0.1% on day 29. M1/M2 marrow on day 29.
LR, low risk; RER, rapid early responder; SER, slow early responder; SR, standard risk; T-LLy, T-cell lymphoblastic lymphoma.