High dose Methotrexate
Methotrexate (MTX) 8 g/m2 iv over 4 hrs q2w till CR or up to 8 cycles, followed by 8 g/m2 iv qm x 11 months

MPV + RT + Ara-C
Methotrexate (MTX) 3.5 g/m2 iv over 2 hours d1
Leucovorin 10 mg q6h x 12 doses starting 24 hours after MTX infusion
Vincristine 1.4 mg/m2 (max 2.8 mg) iv d1
Procarbazine 100 mg/m2 po qd d1-7 cycles 1, 3, 5 only
Q2w x 5 cycles
Intra-ommaya  Methotrexate (MTX) 12 mg on alternate weeks after systemic MTX
Leucovorin 10 mg q6h x 8 doses starting 24 hours after intra-ommaya MTX
3-5 weeks after MPV,  whole-brain radiotherapy (WBRT) 1.8 Gy/d x 25 days to a total of 45 Gy for patients younger than 60 years
3 weeks after WBRT, consolidation Cytarabine (Ara-C) 3 g/m2/d iv over 3 hours for 2 days.  A second cycle of Cytarabine (Ara-C) is given 1 month later

R-MPV + RT + Ara-C
Rituximab (Rituxan)  500 mg/m2 iv over 5 hours d1 of each cycle
Methotrexate (MTX) 3.5 g/m2 iv over 2 hours d2 of each cycle
Leucovorin 20-25 mg q6h starting 24 hours after MTX infusion for 72 hours or until serum MTX level < 1 x 10-8 mg/dL. Increase leucovorin to 40 mg q4h if MTX level > 1 x 10-5 mg/dL at 48 hours or > 1 x 10-8 mg/dL at 72 hours
Vincristine 1.4 mg/m2 (max 2.8 mg) iv d2 of each cycle
Procarbazine 100 mg/m2 po qd d1-7 of odd-numbered cycles only
Filgrastim (Neupogen) 5 mcg/kg/d sc for 3 to 5 days starting 24 hours after the last dose of procarbazine during odd-numbered cycles, and starting 96 hours after MTX infusion or when MTX levels < 1 x 10-8 mg/dL during even-numbered cycles
If positive CSF cytology: intra-ommaya  Methotrexate (MTX) 12 mg between days 5 and 12 of each cycle
Q2w x 5 cycles
After 5 cycles of R-MPV:
If CR, whole-brain radiotherapy (WBRT) 1.8 Gy/d for 13 days to a total of 23.4 Gy beginning 3-5 weeks after the completion of R-MPV
If PR, 2 more additional cycles of R-MPV. If CR after 7 cycles of R-MPV, WBRT 1.8 Gy/d x 13 days to a total of 23.4 Gy beginning 3-5 weeks after the completion of R-MPV. If persistent disease after 7 cycles of R-MPV, WBRT 1.8 Gy/d x 25 days to a total of 45 Gy beginning 3-5 weeks after the completion of R-MPV
If stable disease or progressive disease after 5 cycles of R-MPV, WBRT 1.8 Gy/d x 25 days to a total of 45 Gy beginning 3-5 weeks after the completion of R-MPV
3 weeks after completion of WBRT, consolidation Cytarabine (Ara-C) 3 g/m2/d (max 6 g) iv over 3 hours for 2 days
Filgrastim (Neupogen) 5 mcg/kg/d sc for 10 days starting 48 hours after completion of Ara-C
A second cycle of Cytarabine (Ara-C) is given 1 month later


Bonn protocol

Cycle A (3 wks)
Methotrexate (MTX) 5 g/m2 (3 g/m2 for patients over 65 years old) civi over 24 hrs d1
Vincristine 2 mg iv d1
Ifosfamide 800 mg/m2/d iv over 1 h d2-5
Dexamethasone (Decadron) 10 mg/m2/d po d2-5
Prednisone 2.5 mg intraventricularly qd d2-4
Methotrexate (MTX) 3 mg intraventricularly qd d2-4
Cytarabine (Ara-C) 30 mg intraventricularly d5

Cycle B (3 wks)
Methotrexate (MTX) 5 g/m2 (3 g/m2 for patients over 65 years old) civi over 24 hrs d1
Vincristine 2 mg iv d1
Cyclophosphamide (Cytoxan) 200 mg/m2/d iv over 1 h d2-5
Dexamethasone (Decadron) 10 mg/m2/d po d2-5
Prednisone 2.5 mg intraventricularly qd d2-4
Methotrexate (MTX) 3 mg intraventricularly qd d2-4
Cytarabine (Ara-C) 30 mg intraventricularly d5

Cycle C (3 wks)
Cytarabine (Ara-C) 3 g/m2/d iv over 3 hrs d1-2
Vindesine 5 mg iv d1
Dexamethasone (Decadron) 20 mg/m2/d po d3-7
Prednisone 2.5 mg intraventricularly qd d3-6
Methotrexate (MTX) 3 mg intraventricularly qd d3-6
Cytarabine (Ara-C) 30 mg intraventricularly d7

Sequence of cycles: A (d1-5),  B (d22-26), C (d43-49). Repeat cycles A, B and C once for a total of 6 cycles.
 
MTX + Ara-C + ASCT + RT
Methotrexate (MTX) 8 g/m2 iv over 4 hours d1, 10, 20
Leucovorine rescue 15 mg/m2 q6h until MTX clearance
Cytarabine (Ara-C) 3 g/m2 iv over 3 hours d 30 and 31
Thiotepa 40 mg/m2 iv d 31
Carmustine (BCNU) 400 mg/m2 iv d 50
Thiotepa 5 mg/kg iv d 51, 52
Autologous stem-cell transplantation (ASCT) d56
Hyperfractionated whole brain radiation 2 cycles of 1 Gy/d to 45 Gy for patients with CR or 50 Gy for patients with PR starting d90
Illerhaus G et al. High-dose chemotherapy with autologous stem-cell transplantation and hyperfractionated radiotherapy as first-line treatment of primary CNS lymphoma. J Clin Oncol 2006; 24:3865 (link to the article).

Temozolomide
Temozolomide (Temodar) 150 mg/m2/d po d1-5 q4w
Reni M et al. Temozolomide as salvage treatment in primary brain lymphomas. Br J Cancer 2007; 96:864 (link to the article).

CYVE + ASCT
Cytarabine (Ara-C) 2 g/m2/d iv over 3 hours d2-5 (if 60 years of age and older, reduce to 2 g/m2/d d2-4)
Cytarabine (Ara-C) 50 mg/m2/d iv over 12 hours d1-5
Etoposide (VP-16) 200 mg/m2/d iv over 2 hours d2-5 (if 60 years of age and older, reduce to 150 mg/m2/d d2-5)
Q4w x 2 cycles
Thiotepa 250 mg/m2/d iv d9-7
Busulfan (Myleran) total dose 10 mg/kg po or 8 mg/kg iv d6-4 (if 60 years of age and older, reduce dose by 40%)
Cyclophosphamide (Cytoxan) 60 mg/kg/d d3-2
Autologous stem cell transplantation (ASCT) on d0