Treatment and randomization summary of included studies
| Study ID . | Trial dates . | Reference . | Trial entry criteria (y) . | Risk stratification . | VCR dosage . | Steroid dosage . | Pulse randomization (# analyzed/arm) . | Approximate duration of maintenance or treatment . | EFS (95% CI; %) . |
|---|---|---|---|---|---|---|---|---|---|
| Historical therapy | |||||||||
| SWOG 663/664/ALinC | 1965-1967 | Fernbach et al 1975,34 CALLCG 201010 | Age <15 | — | 2 mg/m2 per wk ×4 | Prednisone 60 mg/m2 per d × 28 d | q 12 wk (44) vs none (56) | Tx: Until relapse | — |
| St. Jude 7 | 1970-1972 | Aur et al 1973,35 CALLCG 201010 | Age <20 | — | 1.5 mg/m2 per wk ×3 | Prednisone 40 mg/m2 per d × 15 d | q 12 wk × 10 (47) vs none (47) | Tx: 2.5 y | 29.8 (20.6-39) |
| HIVH D74 | 1974-1977 | Ortega 198636 | Age <15 | — | 1.5 mg/m2 per wk ×2 | Prednisolone 40 mg/m2 per d × 14 d | q 12 wk × 12 (32) vs none (30) | Tx: 3 y | — |
| DCLSG ALL 3 | 1975-1979 | Van der Does-Van den Berg et al 1998,46 197537 | Age <15 | Standard risk | 2 mg/m2 | Prednisone 40 mg/m2 per d × 14 d | q 7 wk × 14 (79) vs none (68) | Tx: 2 y | 43 (37-49) vs 41 (25-47) |
| CCG 141A 2 | 1978-1979 | Bleyer et al 1983,38 CALLCG 201010 | Age <21 | Nonlow risk | 1.5 mg/m2 | Prednisone 40 mg/m2 per d × 5 d | q 4 wk (150) vs none (151) | Tx: 3 vs 5 y (randomized) | 66.9 (61.6-72.2) |
| CCG 161 | 1978-1983 | Bleyer et al 199139 | Age 36 | Low risk | 1.5 mg/m2 | Prednisone 40 mg/m2 per d × 5 d | q 4 wk (302) vs none (303) | Tx: 2 vs 3 y (randomized) | 76.6 vs 63.9 (P = .003) |
| BFM-79 | 1979-1981 | Henze et al 1981,40 Riehm 199026 | Age <18 | Nonhigh risk | 1.5 mg/m2 per wk ×3 | Prednisone 50 mg/m2 per d × 14 d | q 14 wk × 3 (103) vs none (96) | Mx: 16-18 mo | 76 vs 71 (P = .44) |
| INEN-7902 | 1979-1983 | CALLCG 201010 | — | High risk (unable to confirm) | 1.5 mg/m2 per wk ×2 | Prednisone 100 mg/m2 per d × 14 d | q 8 wk ×4 +/−q 12 wk × 8 (15 vs 17) | Tx: 3 y | 9.1 (0.7-17.5) |
| PETHEMA ALL-84SR | 1984-1989 | CALLCG 201010 | Age <15 | Standard risk (unable to confirm) | 1.5 mg/m2 per wk ×4 | Prednisolone 40 mg/m2 per d × 28 d | q 4 wk × 4 (69) vs none (61) | Tx: 2 y | 55.2 (42.3-68.1) |
| ALL-MB 91 | 1995-2002 | Karachunskiy et al 200828 | Age <18 | All risk groups | 1.5 mg/m2 | Dexamethasone 6 mg/m2 per d × 7 d | q 8 wk (358) vs none (355) | Mx: 18 mo | 67 (64-70) vs 68 (65-71) |
| Contemporary therapy | |||||||||
| CCG-1891 | 1990-1993 | Lange et al 200241 | Age 1-9 | Standard risk | 1.5 mg/m2 | Prednisone 40 mg/m2 per d × 5 d | q 3 wk (397) vs q 4 wk (405) | Mx: 2 y (F), 3 y (M) | 77 (75-79) vs 76 (75-77) |
| I-BFM-SG- ALL IR 95 | 1995-2000 | Conter et al 2007,11 Burger et al 200542 | Age <18 | Intermediate risk | 1.5 mg/m2 | Dexamethasone 6 mg/m2 per d × 7 d | q 10 wk × 6 (1325) vs none (1293) | Mx: 18 mo | 79.8 (77.4-82.2) vs 79.2 (76.8-81.6) |
| AIEOP-ALL-95 | 1995-2000 | Arico et al 2008,48 200343 | Age <18 | Intermediate risk | 1.5 mg/m2 | Dexamethasone 6 mg/m2 per d × 7 d | q 10 wk × 6 (187) vs none (222) | Mx: 18 mo | 84.9 (79.8-90) vs 82.2 (76.9-87.5) |
| EORTC 58951 | 1999-2002 | De Moerloose et al 201044 | Age <18 | Standard & high risk | 1.5 mg/m2 | Prednisone 60 mg/m2 per d vs dexamethasone 6 mg/m2 per d × 7 d | q 10 wk × 6 (167) vs none (163) | Mx: 18 mo | 90.6 (86.5-94.7) vs 82.8 (77.3-88.3) |
| COG AALL 0932 | 2010-2018 | Schore et al 202045 | Age 1-10 + WBC <50, low-risk features | Low risk | 1.5 mg/m2 | Dexamethasone 6 mg/m2 per d ×5 vs 7 d | q 12 wk (302) vs q 16 wk (301) | Mx: 2.5 y vs 2 y (F)/3 y (M) | 98.5 (96.7-100) vs 98.8 (97.2-100) |
| 2010-2018 | Angiolillo et al 202112 | Age 1-10 + WBC <50 | Standard risk | 1.5 mg/m2 | Dexamethasone 6 mg/m2 per d × 5 d | q 4 wk (1186) vs q 12 wk (1178) | Mx: 2 y (F) /3 y (M) | 94.1 (92.2-96.0) vs 95.1 (93.3-96.9) | |
| CCCG ALL 2015 | 2015-2020 | Yang et al 202113 | Age 0-18; LR: low-risk features | Low risk | 1.5 mg/m2 | Dexamethasone 6 mg/m2 per d × 7 d | q 4 wk × 1 y then q 8 wk × 7 (1442) vs stop (1481) | Tx: 2.5 y | 90.3 (88.4-92.2) vs 90.2 (88.2-92.2) |
| Study ID . | Trial dates . | Reference . | Trial entry criteria (y) . | Risk stratification . | VCR dosage . | Steroid dosage . | Pulse randomization (# analyzed/arm) . | Approximate duration of maintenance or treatment . | EFS (95% CI; %) . |
|---|---|---|---|---|---|---|---|---|---|
| Historical therapy | |||||||||
| SWOG 663/664/ALinC | 1965-1967 | Fernbach et al 1975,34 CALLCG 201010 | Age <15 | — | 2 mg/m2 per wk ×4 | Prednisone 60 mg/m2 per d × 28 d | q 12 wk (44) vs none (56) | Tx: Until relapse | — |
| St. Jude 7 | 1970-1972 | Aur et al 1973,35 CALLCG 201010 | Age <20 | — | 1.5 mg/m2 per wk ×3 | Prednisone 40 mg/m2 per d × 15 d | q 12 wk × 10 (47) vs none (47) | Tx: 2.5 y | 29.8 (20.6-39) |
| HIVH D74 | 1974-1977 | Ortega 198636 | Age <15 | — | 1.5 mg/m2 per wk ×2 | Prednisolone 40 mg/m2 per d × 14 d | q 12 wk × 12 (32) vs none (30) | Tx: 3 y | — |
| DCLSG ALL 3 | 1975-1979 | Van der Does-Van den Berg et al 1998,46 197537 | Age <15 | Standard risk | 2 mg/m2 | Prednisone 40 mg/m2 per d × 14 d | q 7 wk × 14 (79) vs none (68) | Tx: 2 y | 43 (37-49) vs 41 (25-47) |
| CCG 141A 2 | 1978-1979 | Bleyer et al 1983,38 CALLCG 201010 | Age <21 | Nonlow risk | 1.5 mg/m2 | Prednisone 40 mg/m2 per d × 5 d | q 4 wk (150) vs none (151) | Tx: 3 vs 5 y (randomized) | 66.9 (61.6-72.2) |
| CCG 161 | 1978-1983 | Bleyer et al 199139 | Age 36 | Low risk | 1.5 mg/m2 | Prednisone 40 mg/m2 per d × 5 d | q 4 wk (302) vs none (303) | Tx: 2 vs 3 y (randomized) | 76.6 vs 63.9 (P = .003) |
| BFM-79 | 1979-1981 | Henze et al 1981,40 Riehm 199026 | Age <18 | Nonhigh risk | 1.5 mg/m2 per wk ×3 | Prednisone 50 mg/m2 per d × 14 d | q 14 wk × 3 (103) vs none (96) | Mx: 16-18 mo | 76 vs 71 (P = .44) |
| INEN-7902 | 1979-1983 | CALLCG 201010 | — | High risk (unable to confirm) | 1.5 mg/m2 per wk ×2 | Prednisone 100 mg/m2 per d × 14 d | q 8 wk ×4 +/−q 12 wk × 8 (15 vs 17) | Tx: 3 y | 9.1 (0.7-17.5) |
| PETHEMA ALL-84SR | 1984-1989 | CALLCG 201010 | Age <15 | Standard risk (unable to confirm) | 1.5 mg/m2 per wk ×4 | Prednisolone 40 mg/m2 per d × 28 d | q 4 wk × 4 (69) vs none (61) | Tx: 2 y | 55.2 (42.3-68.1) |
| ALL-MB 91 | 1995-2002 | Karachunskiy et al 200828 | Age <18 | All risk groups | 1.5 mg/m2 | Dexamethasone 6 mg/m2 per d × 7 d | q 8 wk (358) vs none (355) | Mx: 18 mo | 67 (64-70) vs 68 (65-71) |
| Contemporary therapy | |||||||||
| CCG-1891 | 1990-1993 | Lange et al 200241 | Age 1-9 | Standard risk | 1.5 mg/m2 | Prednisone 40 mg/m2 per d × 5 d | q 3 wk (397) vs q 4 wk (405) | Mx: 2 y (F), 3 y (M) | 77 (75-79) vs 76 (75-77) |
| I-BFM-SG- ALL IR 95 | 1995-2000 | Conter et al 2007,11 Burger et al 200542 | Age <18 | Intermediate risk | 1.5 mg/m2 | Dexamethasone 6 mg/m2 per d × 7 d | q 10 wk × 6 (1325) vs none (1293) | Mx: 18 mo | 79.8 (77.4-82.2) vs 79.2 (76.8-81.6) |
| AIEOP-ALL-95 | 1995-2000 | Arico et al 2008,48 200343 | Age <18 | Intermediate risk | 1.5 mg/m2 | Dexamethasone 6 mg/m2 per d × 7 d | q 10 wk × 6 (187) vs none (222) | Mx: 18 mo | 84.9 (79.8-90) vs 82.2 (76.9-87.5) |
| EORTC 58951 | 1999-2002 | De Moerloose et al 201044 | Age <18 | Standard & high risk | 1.5 mg/m2 | Prednisone 60 mg/m2 per d vs dexamethasone 6 mg/m2 per d × 7 d | q 10 wk × 6 (167) vs none (163) | Mx: 18 mo | 90.6 (86.5-94.7) vs 82.8 (77.3-88.3) |
| COG AALL 0932 | 2010-2018 | Schore et al 202045 | Age 1-10 + WBC <50, low-risk features | Low risk | 1.5 mg/m2 | Dexamethasone 6 mg/m2 per d ×5 vs 7 d | q 12 wk (302) vs q 16 wk (301) | Mx: 2.5 y vs 2 y (F)/3 y (M) | 98.5 (96.7-100) vs 98.8 (97.2-100) |
| 2010-2018 | Angiolillo et al 202112 | Age 1-10 + WBC <50 | Standard risk | 1.5 mg/m2 | Dexamethasone 6 mg/m2 per d × 5 d | q 4 wk (1186) vs q 12 wk (1178) | Mx: 2 y (F) /3 y (M) | 94.1 (92.2-96.0) vs 95.1 (93.3-96.9) | |
| CCCG ALL 2015 | 2015-2020 | Yang et al 202113 | Age 0-18; LR: low-risk features | Low risk | 1.5 mg/m2 | Dexamethasone 6 mg/m2 per d × 7 d | q 4 wk × 1 y then q 8 wk × 7 (1442) vs stop (1481) | Tx: 2.5 y | 90.3 (88.4-92.2) vs 90.2 (88.2-92.2) |
F, female; LR, low risk; M, male; Mx, maintainance; Tx, treatment; q, every; WBC, white blood cell.