Induction and consolidation phases
| Day . | Drug/dose/administration schedule . |
|---|---|
| Induction | |
| −2 | Methylprednisolone 0.5-1 mg/kg per d IV |
| −1 | Methylprednisolone 0.5-1 mg/kg per d IV |
| 0 | Methylprednisolone 0.5-1 mg/kg per d IVCyclophosphamide 500 mg/m2 over 1-h infusionVincristine 2 mg total dose IV bolus |
| 1 | Methylprednisolone 0.5-1 mg/kg per d IVCyclophosphamide 500 mg/m2 over 1-h infusion |
| 2 | Rituximab 375 mg/m2 |
| 5 | Methotrexate 12 mg + cytarabine 50 mg + steroids by IT route |
| 7 | Methotrexate 3 g/m2 IV over 6 h with leucovorin rescue therapy∗ |
| 14 | Rituximab 375 mg/m2 |
| 15 | Etoposide 250 mg/m2 every 12 h |
| 19 | Methotrexate 12 mg + cytarabine 50 mg + steroids by IT route |
| 21 | Methotrexate 3 g/m2 IV over 6 h with leucovorin rescue therapy# |
| 29 | Rituximab 375 mg/m2Doxorubicin 50 mg/m2 IV bolus |
| 33 | Methotrexate 12 mg + cytarabine 50 mg + steroids by IT route |
| 36 | Rituximab 375 mg/m2Vincristine 2 mg total dose IV bolus |
| Consolidation† | |
| HIV− | |
| 50-53 | Cytarabine 750 mg/m2 followed 3 h later by 1 g/m2 by 24-h infusionCisplatin 20 mg/m2 per d by 24-h infusion |
| 56 | Rituximab 375 mg/m2 |
| HIV+ | |
| 50-51 | Cytarabine 2 g/m2 in a 3-h infusion twice a day (every 12 h) |
| 52 | Rituximab 375 mg/m2 |
| 60 | Rituximab 375 mg/m2 |
| Day . | Drug/dose/administration schedule . |
|---|---|
| Induction | |
| −2 | Methylprednisolone 0.5-1 mg/kg per d IV |
| −1 | Methylprednisolone 0.5-1 mg/kg per d IV |
| 0 | Methylprednisolone 0.5-1 mg/kg per d IVCyclophosphamide 500 mg/m2 over 1-h infusionVincristine 2 mg total dose IV bolus |
| 1 | Methylprednisolone 0.5-1 mg/kg per d IVCyclophosphamide 500 mg/m2 over 1-h infusion |
| 2 | Rituximab 375 mg/m2 |
| 5 | Methotrexate 12 mg + cytarabine 50 mg + steroids by IT route |
| 7 | Methotrexate 3 g/m2 IV over 6 h with leucovorin rescue therapy∗ |
| 14 | Rituximab 375 mg/m2 |
| 15 | Etoposide 250 mg/m2 every 12 h |
| 19 | Methotrexate 12 mg + cytarabine 50 mg + steroids by IT route |
| 21 | Methotrexate 3 g/m2 IV over 6 h with leucovorin rescue therapy# |
| 29 | Rituximab 375 mg/m2Doxorubicin 50 mg/m2 IV bolus |
| 33 | Methotrexate 12 mg + cytarabine 50 mg + steroids by IT route |
| 36 | Rituximab 375 mg/m2Vincristine 2 mg total dose IV bolus |
| Consolidation† | |
| HIV− | |
| 50-53 | Cytarabine 750 mg/m2 followed 3 h later by 1 g/m2 by 24-h infusionCisplatin 20 mg/m2 per d by 24-h infusion |
| 56 | Rituximab 375 mg/m2 |
| HIV+ | |
| 50-51 | Cytarabine 2 g/m2 in a 3-h infusion twice a day (every 12 h) |
| 52 | Rituximab 375 mg/m2 |
| 60 | Rituximab 375 mg/m2 |
Dose intensity was maintained using granulocyte colony-stimulating factor whenever neutrophil count was ≤ 1.5 × 109/L. Antimicrobial prophylaxis (acyclovir 400 mg twice per day, fluconazole 100-200 mg once a day, and trimethoprim 160 mg/sulfamethoxazole 800 mg 3 times per week) was used. Levofloxacin 500 mg/d was added in patients with grade 4 neutropenia. Prophylaxis and treatment of HBV infection followed national guidelines. In brief, carriers of active infection (hepatitis B surface antigen (HbsAg) positivity and HBV DNA >2.000 IU) were treated with entecavir; carriers of inactive infection (HBV DNA undetectable levels) and carriers of occult infection (negative HbsAg, negative HBV DNA, and positive HBcAb) were treated with lamivudine (entecavir 0.5 mg/d for selected patients). Duration of prophylaxis was 12 months in HBsAg+ patients and 18 months in occult infection carriers. HBV reactivation was treated with tenofovir (entecavir 1 mg/d in case of renal dysfunction). HCV infection was monitored with frequent assessment of hepatic transaminases and HCV RNA level.
IT, intrathecal route.
IV alkalinization was used to promote excretion of methotrexate according to institutional guidelines. Calcium leucovorin was administered at a dose of 15 mg/m2 IV starting 24 hours after completing methotrexate infusion and continued every 6 hours for 12 doses or, in excess, until methotrexate blood levels were <0·2 μmol/L. Methotrexate serum levels were monitored at 48, 72, and 96 hours from methotrexate infusion, and leucovorin dose was adjusted according to methotrexate serum levels.
Methotrexate dose was 5 g/m2 in day 21 in HIV-negative patients.
Leukapheresis to collect autologous peripheral-blood stem cells was performed after consolidation, starting granulocyte colony-stimulating factor 24 hours after the last dose of cytarabine.