Treatment stratification and results in two recent multicenter trials on pediatric B-cell non-Hodgkin lymphoma.
| FAB/LMB 9629,31,32 . | . | . | . | . | . | Cumulative doses . | |||
|---|---|---|---|---|---|---|---|---|---|
| Group . | Definition . | N= 1134 . | pEFS . | Chemotherapy courses . | MTX g/m2 . | CP g/m2 . | Ifo g/m2 . | Doxo mg/m2 . | Eto mg/m2 . |
| A | Stage I-resected | 12% | 98% | COPAD-COPAD | 0 | 3 | 0 | 120 | 0 |
| II-abdominal | (3 y) | ||||||||
| B | I-not resected | 67% | 90% | COP-COPADM1-*COPADM2‡-CYM-CYM-M1 | 3, ×5 | 5.8 | 0 | 180 | 0 |
| II-non-abdominal, III, IV | (4 y) | *COPADM2‡-CYM-CYM | 3, ×4 | 4.8 | 0 | 120 | 0 | ||
| BM-blasts ≤ 25% | *COPADM1-CYM-CYM-M1 | 3, ×5 | 4.3 | 0 | 180 | 0 | |||
| CNS− | *COPADM1-CYM-CYM† | 3, ×4 | 3.3 | 0 | 120 | 0 | |||
| C | >25% BM-blasts and/or CNS+ | 21% | 79% | COP-COPADM1-COPADM2-CYVE1-(CNS+only: HD-MTX)- | 8, ×3 | 6.8 | 0 | 240 | 2500 |
| (4 y) | CYVE2- M1- M2- M3- M4 | (×4 for CNS+) | R | R | |||||
| Randomization for responders after COP-COPADM1+2: | 5.8 | 0 | 180 | 800 | |||||
| Reduced intensity “mini-CYVE” and omission M2, M3, M4. | |||||||||
| Result: inferior outcome | |||||||||
| FAB/LMB 9629,31,32 . | . | . | . | . | . | Cumulative doses . | |||
|---|---|---|---|---|---|---|---|---|---|
| Group . | Definition . | N= 1134 . | pEFS . | Chemotherapy courses . | MTX g/m2 . | CP g/m2 . | Ifo g/m2 . | Doxo mg/m2 . | Eto mg/m2 . |
| A | Stage I-resected | 12% | 98% | COPAD-COPAD | 0 | 3 | 0 | 120 | 0 |
| II-abdominal | (3 y) | ||||||||
| B | I-not resected | 67% | 90% | COP-COPADM1-*COPADM2‡-CYM-CYM-M1 | 3, ×5 | 5.8 | 0 | 180 | 0 |
| II-non-abdominal, III, IV | (4 y) | *COPADM2‡-CYM-CYM | 3, ×4 | 4.8 | 0 | 120 | 0 | ||
| BM-blasts ≤ 25% | *COPADM1-CYM-CYM-M1 | 3, ×5 | 4.3 | 0 | 180 | 0 | |||
| CNS− | *COPADM1-CYM-CYM† | 3, ×4 | 3.3 | 0 | 120 | 0 | |||
| C | >25% BM-blasts and/or CNS+ | 21% | 79% | COP-COPADM1-COPADM2-CYVE1-(CNS+only: HD-MTX)- | 8, ×3 | 6.8 | 0 | 240 | 2500 |
| (4 y) | CYVE2- M1- M2- M3- M4 | (×4 for CNS+) | R | R | |||||
| Randomization for responders after COP-COPADM1+2: | 5.8 | 0 | 180 | 800 | |||||
| Reduced intensity “mini-CYVE” and omission M2, M3, M4. | |||||||||
| Result: inferior outcome | |||||||||
| NHL-BFM 9526 . | . | . | . | . | . | . | . | . | . |
|---|---|---|---|---|---|---|---|---|---|
| Group . | Definition . | N= 505 . | pEFS . | Chemotherapy courses . | . | . | . | . | . |
| Abbreviations: P, cytoreductive prophase; MTX, methotrexate; CP, cyclophosphamide; Ifo, ifosfamide; Doxo, doxorubicin; Eto, etoposide; R, randomization; y, years; hr, hours; iv, intravenously; CNS, central nervous system; BM, bone marrow | |||||||||
| *Factorial design randomization for responders to COP-COPADM1. | |||||||||
| †Equally efficacious. | |||||||||
| ‡Dose of cyclophosphamide 3 g/m2in COPADM2 compared with 1.5 g/m2in COPADM1. | |||||||||
| R1 | Stage I+II–resected | 10% | 94% | A- B | 1, ×2 | 1.4 | 4 | 50 | 200 |
| (3 y) | Randomization: MTX iv over 24 hr vs 4 hr | ||||||||
| Result: 4 hr less toxic, equally efficacious | |||||||||
| R2 | I+II–not resected | 46% | 94% | P-A- B- A- B | 1, ×4 | 2.4 | 8 | 100 | 400 |
| III-LDH <500/U/L | (3 y) | Randomization: MTX iv over 24 hr vs 4 hr | |||||||
| Result: 4 hr less toxic, equally efficacious | |||||||||
| R3 | III-LDH 500 <999 U/L | 16% | 85% | P-AA- BB- CC- AA- BB | 5, ×4 | 2.4 | 8 | 100 | 900 |
| BM+and LDH <1000 U/L | (3 y) | Randomization: MTX in AA, BB iv over 24 hr vs 4 hr: | |||||||
| Result: 4 hr less toxic, less efficacious | |||||||||
| R4 | LDH≥1000 U/L and/or CNS+ | 28% | 81% | P-AA- BB- CC- AA- BB- CC | 5, ×4 | 2.4 | 8 | 100 | 1400 |
| (3 y) | Randomization: MTX in AA, BB iv over 24 hr vs 4 hr. | ||||||||
| Result: 4 hr less toxic, less efficacious | |||||||||
| NHL-BFM 9526 . | . | . | . | . | . | . | . | . | . |
|---|---|---|---|---|---|---|---|---|---|
| Group . | Definition . | N= 505 . | pEFS . | Chemotherapy courses . | . | . | . | . | . |
| Abbreviations: P, cytoreductive prophase; MTX, methotrexate; CP, cyclophosphamide; Ifo, ifosfamide; Doxo, doxorubicin; Eto, etoposide; R, randomization; y, years; hr, hours; iv, intravenously; CNS, central nervous system; BM, bone marrow | |||||||||
| *Factorial design randomization for responders to COP-COPADM1. | |||||||||
| †Equally efficacious. | |||||||||
| ‡Dose of cyclophosphamide 3 g/m2in COPADM2 compared with 1.5 g/m2in COPADM1. | |||||||||
| R1 | Stage I+II–resected | 10% | 94% | A- B | 1, ×2 | 1.4 | 4 | 50 | 200 |
| (3 y) | Randomization: MTX iv over 24 hr vs 4 hr | ||||||||
| Result: 4 hr less toxic, equally efficacious | |||||||||
| R2 | I+II–not resected | 46% | 94% | P-A- B- A- B | 1, ×4 | 2.4 | 8 | 100 | 400 |
| III-LDH <500/U/L | (3 y) | Randomization: MTX iv over 24 hr vs 4 hr | |||||||
| Result: 4 hr less toxic, equally efficacious | |||||||||
| R3 | III-LDH 500 <999 U/L | 16% | 85% | P-AA- BB- CC- AA- BB | 5, ×4 | 2.4 | 8 | 100 | 900 |
| BM+and LDH <1000 U/L | (3 y) | Randomization: MTX in AA, BB iv over 24 hr vs 4 hr: | |||||||
| Result: 4 hr less toxic, less efficacious | |||||||||
| R4 | LDH≥1000 U/L and/or CNS+ | 28% | 81% | P-AA- BB- CC- AA- BB- CC | 5, ×4 | 2.4 | 8 | 100 | 1400 |
| (3 y) | Randomization: MTX in AA, BB iv over 24 hr vs 4 hr. | ||||||||
| Result: 4 hr less toxic, less efficacious | |||||||||