Examples of common regimens used for adults with ALL, schedule of CNS-directed therapy, and rates of relapse in the CNS
| Study . | Enrollment period . | CNS involvement at diagnosis (%) . | CNS-directed therapy . | CNS relapse rates (%) . |
|---|---|---|---|---|
| Hyper-CVAD1 | 1992-1998 | 7 | CNS-negative: between 4-16 doses of IT chemotherapy (alternating MTX and ARA-C) over ∼6 mo, depending on risk category∗ CNS-positive: twice weekly IT chemotherapy until CSF cleared (then IT prophylaxis per risk category), followed by remaining prophylaxis schedule plus 24-30 Gy cranial RT, if cranial nerve involvement Systemic therapy: dexamethasone, high-dose MTX, and high-dose ARA-C | 4 |
| MRC UKALL XII/ECOG E29932 | 1993-2003 | 5 | CNS-negative: IT MTX × 5 given through phase 2 (∼2 mo) CNS-positive: weekly IT MTX until CSF cleared plus 24 Gy cranial RT and 12 Gy spinal RT Systemic therapy: l-asparaginase, 6-MP, and high-dose MTX | 4 |
| GRAALL 20053 | 2006-2014 | 5 | CNS-negative: IT MTX × 1 in prephase; ITT × 6 through late intensification (∼6 mo) ± 18 Gy cranial RT†, CNS-positive: ITT × 14 through first consolidation (∼2 mo) plus 15 to 24 Gy cranial RT† Systemic therapy: l-asparaginase, high-dose ARA-C, dexamethasone, high-dose MTX, and 6-MP | 5 |
| CALGB 104034 | 2007-2012 | 10.5 | CNS-negative: IT ARA-C × 1 and IT MTX × 11 during the first 4 courses (∼7 mo) of therapy, then continued during prolonged maintenance‡ CNS-positive: same total doses of IT chemotherapy but weekly during remission induction plus 18 Gy cranial RT Systemic therapy: pegaspargase, 6-MP, dexamethasone, and thioguanine | Not reported |
| Study . | Enrollment period . | CNS involvement at diagnosis (%) . | CNS-directed therapy . | CNS relapse rates (%) . |
|---|---|---|---|---|
| Hyper-CVAD1 | 1992-1998 | 7 | CNS-negative: between 4-16 doses of IT chemotherapy (alternating MTX and ARA-C) over ∼6 mo, depending on risk category∗ CNS-positive: twice weekly IT chemotherapy until CSF cleared (then IT prophylaxis per risk category), followed by remaining prophylaxis schedule plus 24-30 Gy cranial RT, if cranial nerve involvement Systemic therapy: dexamethasone, high-dose MTX, and high-dose ARA-C | 4 |
| MRC UKALL XII/ECOG E29932 | 1993-2003 | 5 | CNS-negative: IT MTX × 5 given through phase 2 (∼2 mo) CNS-positive: weekly IT MTX until CSF cleared plus 24 Gy cranial RT and 12 Gy spinal RT Systemic therapy: l-asparaginase, 6-MP, and high-dose MTX | 4 |
| GRAALL 20053 | 2006-2014 | 5 | CNS-negative: IT MTX × 1 in prephase; ITT × 6 through late intensification (∼6 mo) ± 18 Gy cranial RT†, CNS-positive: ITT × 14 through first consolidation (∼2 mo) plus 15 to 24 Gy cranial RT† Systemic therapy: l-asparaginase, high-dose ARA-C, dexamethasone, high-dose MTX, and 6-MP | 5 |
| CALGB 104034 | 2007-2012 | 10.5 | CNS-negative: IT ARA-C × 1 and IT MTX × 11 during the first 4 courses (∼7 mo) of therapy, then continued during prolonged maintenance‡ CNS-positive: same total doses of IT chemotherapy but weekly during remission induction plus 18 Gy cranial RT Systemic therapy: pegaspargase, 6-MP, dexamethasone, and thioguanine | Not reported |
ARA-C, cytarabine; MTX, methotrexate; 6-MP, 6-mercaptopurine.
Patients were considered at high risk if LDH levels were >600 units per L or with a proliferative index >14%.
RT treatment was based on candidacy for HCT: patients who had CNS-negative results and were candidates for HCT were not given prophylactic RT, whereas patients who were not eligible for HCT received 18 Gy cranial RT; patients who had CNS-positive results and were candidates for HCT received 15 Gy cranial RT, whereas patients who were not eligible for HCT were given 24 Gy.
Patients with T-cell phenotype also received 24 Gy cranial RT during first maintenance cycle.