Selection of salvage regimens used in relapsed/refractory adult Ph− ALL
| Chemotherapy . | Regimen . | Patients . | Results . | Reference . |
|---|---|---|---|---|
| High-dose cytarabine + anthracycline | Cytarabine: 3 g/m2 on days 1-5 Idarubicin: 40 mg/m2 on day 3 | N = 29 (age >15 y) n = 21 relapsed n = 8 refractory | CR = 38%; 14% to SCT; TRM = 3% | 26 |
| Cytarabine: 3 g/m2 on days 1-5 Idarubicin: 40 mg/m2 on day 3 | N = 135 (median age 30 y) Relapsed & refractory | CR = 55%; 40% to SCT; TRM = 12% | 25 | |
| Cytarabine: 3 g/m2 on days 1-5 Mitoxantrone: 80 mg/m2 on day 1 | N = 31 (age >16 y) No prior cytarabine | CR = 23%; 1 patient to SCT; TRM = 16% | 27 | |
| Cytarabine: 3 g/m2 on days 1-5 Mitoxantrone: 40-60 mg/m2 on day 1 | N = 11 | CR = 53%; TRM = 6% | 29 | |
| Cytarabine: 1 g/m2 every 12 h on days 1-5 Etoposide: 100 mg/m2 on days 1-5 Amsacrine 120 mg/m2 on days 1-3 | N = 40 All relapsed | CR = 40%; 10% to SCT | 28 | |
| FLAG-based | FLAG (1-2 cycles) Fludarabine: 30 mg/m2 on days 1-5 Cytarabine: 2 g/m2 on days 1-5 G-CSF | N=12 First relapse only | CR = 83%; TRM = 8% | 30 |
| FLAG-IDA (2 cycles) Fludarabine: 30 mg/m2 on days 1-5 Cytarabine: 2 g/m2 on days 1-5 Idarubicin: 10 mg/m2 on days 1-5 G-CSF | N=23 Relapsed/refractory | CR = 39%; 30% to SCT; TRM = 4% | 31 | |
| FLAG-IDA Fludarabine: 25 mg/m2 × 5 d Cytarabine 2 g/m2 × 5 d Idarubicin: 12 mg/m2 × 3 d G-CSF | N = 22 Relapsed/refractory | CR = 42% | 32 | |
| Hyper-CVAD–based | Hyper-CVAD (8 cycles alternating A and B) A: Cy, vincristine, doxorubicin, dexamethasone B: High-dose methotrexate and cytarabine | N = 66 n = 10 refractory n = 56 relapsed | CR = 44% | 34 |
| Augmented hyper-CVAD (8 cycles alternating A and B) Incorporates l-asparaginase* or peg-asparaginase and additional dexamethasone and vincristine doses into cycles | N = 88 (median age 34 y) n = 10 refractory n = 78 relapsed | CR = 47%; 32% to SCT; TRM = 9% | 33 | |
| Clofarabine-based | Clofarabine: 40 mg/m2 on days 1-5 | N = 12 (median age 54 y) Relapsed/refractory | CR = 17% | 37 |
| Clofarabine based (PETHEMA) n = 5 clofarabine alone n = 12 clofarabine + Cy n = 8 clofarabine + Cy + etoposide n = 6 clofarabine + cytarabine | N = 31 (median age 33 y) Relapsed/refractory Heavily pretreated | CR = 31%; 19% to SCT; TRM = 23% | 40 | |
| Clofarabine: 40 mg/m2 on days 1-5 Cytarabine: 1 g/m2 on days 1-5 | N = 37 (median age 41 y) Relapsed/refractory | CR = 17%; 21% to SCT; TRM = 19% | 39 | |
| Clofarabine: 20-25 mg/m2 on days 1-5 Etoposide: 100 mg/m2 on days 1-5 Mitoxantrone: 8 mg/m2 on days 1-3 | N = 4 Relapsed/refractory | CR = 50% (ALL); TRM = 9% (AML & ALL) | 38 | |
| Other combinations | Berlin-Frankfurt-Munster–like | N = 50 (age 18-53 y) | 58% CR | 35 |
| Mitoxantrone: 8 mg/m2 × 3 Etoposide: 100 mg/m2 × 5 Ifosfamide: 1.5 g /m2 × 5 | N = 11 | CR = 73% | 41 | |
| 5-Day induction vindesine, mitoxantrone, cyclophosphamide, cytarabine, methotrexate, prednisolone | N = 45 n = 17 refractory n = 28 relapsed | CR = 74%; 31% to SCT; TRM = 4% | 36 | |
| Liposomal vincristine | Liposomal vincristine: 2.25 mg/m2 weekly | N = 65 Relapsed Heavily pretreated | CR = 20%; PR = 15%; 19% to SCT | 16 |
| Nelarabine | Nelarabine: 1.5 g/m2 on days 1, 3, 5 | N = 26 (aged 16-64 y) T-cell ALL No CNS disease | CR = 31%; PR = 10% | 15 |
| Nelarabine: 1.5 g/m2 on days 1, 3, 5 | N = 126 (aged 18-81 y) T-cell ALL Relapsed/refractory | CR = 36%; PR = 10%; 29% to SCT; TRM ≤1% | 42 |
| Chemotherapy . | Regimen . | Patients . | Results . | Reference . |
|---|---|---|---|---|
| High-dose cytarabine + anthracycline | Cytarabine: 3 g/m2 on days 1-5 Idarubicin: 40 mg/m2 on day 3 | N = 29 (age >15 y) n = 21 relapsed n = 8 refractory | CR = 38%; 14% to SCT; TRM = 3% | 26 |
| Cytarabine: 3 g/m2 on days 1-5 Idarubicin: 40 mg/m2 on day 3 | N = 135 (median age 30 y) Relapsed & refractory | CR = 55%; 40% to SCT; TRM = 12% | 25 | |
| Cytarabine: 3 g/m2 on days 1-5 Mitoxantrone: 80 mg/m2 on day 1 | N = 31 (age >16 y) No prior cytarabine | CR = 23%; 1 patient to SCT; TRM = 16% | 27 | |
| Cytarabine: 3 g/m2 on days 1-5 Mitoxantrone: 40-60 mg/m2 on day 1 | N = 11 | CR = 53%; TRM = 6% | 29 | |
| Cytarabine: 1 g/m2 every 12 h on days 1-5 Etoposide: 100 mg/m2 on days 1-5 Amsacrine 120 mg/m2 on days 1-3 | N = 40 All relapsed | CR = 40%; 10% to SCT | 28 | |
| FLAG-based | FLAG (1-2 cycles) Fludarabine: 30 mg/m2 on days 1-5 Cytarabine: 2 g/m2 on days 1-5 G-CSF | N=12 First relapse only | CR = 83%; TRM = 8% | 30 |
| FLAG-IDA (2 cycles) Fludarabine: 30 mg/m2 on days 1-5 Cytarabine: 2 g/m2 on days 1-5 Idarubicin: 10 mg/m2 on days 1-5 G-CSF | N=23 Relapsed/refractory | CR = 39%; 30% to SCT; TRM = 4% | 31 | |
| FLAG-IDA Fludarabine: 25 mg/m2 × 5 d Cytarabine 2 g/m2 × 5 d Idarubicin: 12 mg/m2 × 3 d G-CSF | N = 22 Relapsed/refractory | CR = 42% | 32 | |
| Hyper-CVAD–based | Hyper-CVAD (8 cycles alternating A and B) A: Cy, vincristine, doxorubicin, dexamethasone B: High-dose methotrexate and cytarabine | N = 66 n = 10 refractory n = 56 relapsed | CR = 44% | 34 |
| Augmented hyper-CVAD (8 cycles alternating A and B) Incorporates l-asparaginase* or peg-asparaginase and additional dexamethasone and vincristine doses into cycles | N = 88 (median age 34 y) n = 10 refractory n = 78 relapsed | CR = 47%; 32% to SCT; TRM = 9% | 33 | |
| Clofarabine-based | Clofarabine: 40 mg/m2 on days 1-5 | N = 12 (median age 54 y) Relapsed/refractory | CR = 17% | 37 |
| Clofarabine based (PETHEMA) n = 5 clofarabine alone n = 12 clofarabine + Cy n = 8 clofarabine + Cy + etoposide n = 6 clofarabine + cytarabine | N = 31 (median age 33 y) Relapsed/refractory Heavily pretreated | CR = 31%; 19% to SCT; TRM = 23% | 40 | |
| Clofarabine: 40 mg/m2 on days 1-5 Cytarabine: 1 g/m2 on days 1-5 | N = 37 (median age 41 y) Relapsed/refractory | CR = 17%; 21% to SCT; TRM = 19% | 39 | |
| Clofarabine: 20-25 mg/m2 on days 1-5 Etoposide: 100 mg/m2 on days 1-5 Mitoxantrone: 8 mg/m2 on days 1-3 | N = 4 Relapsed/refractory | CR = 50% (ALL); TRM = 9% (AML & ALL) | 38 | |
| Other combinations | Berlin-Frankfurt-Munster–like | N = 50 (age 18-53 y) | 58% CR | 35 |
| Mitoxantrone: 8 mg/m2 × 3 Etoposide: 100 mg/m2 × 5 Ifosfamide: 1.5 g /m2 × 5 | N = 11 | CR = 73% | 41 | |
| 5-Day induction vindesine, mitoxantrone, cyclophosphamide, cytarabine, methotrexate, prednisolone | N = 45 n = 17 refractory n = 28 relapsed | CR = 74%; 31% to SCT; TRM = 4% | 36 | |
| Liposomal vincristine | Liposomal vincristine: 2.25 mg/m2 weekly | N = 65 Relapsed Heavily pretreated | CR = 20%; PR = 15%; 19% to SCT | 16 |
| Nelarabine | Nelarabine: 1.5 g/m2 on days 1, 3, 5 | N = 26 (aged 16-64 y) T-cell ALL No CNS disease | CR = 31%; PR = 10% | 15 |
| Nelarabine: 1.5 g/m2 on days 1, 3, 5 | N = 126 (aged 18-81 y) T-cell ALL Relapsed/refractory | CR = 36%; PR = 10%; 29% to SCT; TRM ≤1% | 42 |
Cy, cyclophosphamide; FLAG, fludarabine/high-dose cytarabine/G-CSF; G-CSF, granulocyte colony-stimulating factor; IDA, idarubicin; PETHEMA, Programa Español de Tratamiento en Hematologia; PR, partial remission; TRM, treatment-related mortality.
l-asparaginase is not currently commercially available.