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Home > LYM NHL B-cell PCNSL - R-MPV [RITUximab, metHOTREXATe, procarbazine and vinCRISTine] followed by high dose cytarabine > LYM - R-MPV alternating with R-MV

This regimen is a component of LYM NHL B-cell PCNSL - R-MPV [RITUximab, metHOTREXATe, procarbazine and vinCRISTine] followed by high dose cytarabine

R-MPV alternating with R-MV Induction (LYM NHL B-cell PCNSL - R-MPV [RITUximab, metHOTREXATe, procarbazine and vinCRISTine] followed by high dose cytarabine)

Treatment Overview

Alternating cycles of R-MPV and R-MV, every 14 to 21 days (on count recovery) for

5 cycles if in complete remission after 5 cycles.
7 cycles if in partial remission after 5 cycles (administer 2 additional cycles as cycle 6 and 7).

High dose metHOTREXATe

metHOTREXATe levels MUST be measured once every 24 hours.
Intravenous alkalinized fluids MUST be commenced at least 6 hours before the start of metHOTREXATe infusion and MUST continue until the metHOTREXATe serum level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice). Additional oral alkalinization can be considered as Ural® 2 sachets orally the night before and 2 sachets the morning of high dose metHOTREXATe infusion.
Before commencing the high dose metHOTREXATe infusion, urinary pH MUST be 7.5 or above (pH 7.5 to 8.0).
Closely monitor renal function, electrolytes, fluid balance, and weight.
foliNIc acid MUST start 24 hours after start of metHOTREXATe infusion and MUST continue to be administered until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).

Intrathecal therapy

Required if CSF cytology/flow positive at diagnosis and after 2 cycles of Induction.
See LYM NHL B-cell - Intrathecal Triple Therapy [metHOTREXATe, cytarabine and hydrocortisone].

This regimen contains a medicine where one or more biosimilars may exist. Any biosimilars used have been reviewed by the regulator (Medsafe) and relevant specialists were consulted nationally. Where regulators, in consultation with relevant specialists, have agreed that there are no clinically significant differences in either safety or effectiveness between a biosimilar and originator product, these drugs may be used interchangeably.

Cycle 1 - 14 days - R-MPV [RITUximab (first dose), metHOTREXATe, procarbazine and vinCRISTine]

Cycle length:

RITUximab, first dose:

Consider withholding routine anti-hypertensives for 12 hours prior to first RITUximab dose.
For patients at high risk of infusion-related reaction, consider additional pre-medications such as an extra antihistamine dose the day before, an H₂ receptor antagonist and montelukast.
Some centres may choose to use RITUximab 500 mg/m² as per Morris et al 2013.

foliNIc acid:

MUST start 24 hours after start of metHOTREXATe infusion and MUST continue to be administered every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
Some centres can consider using an alternative dosing strategy for certain patients commencing 24 hours after the start of the metHOTREXATe infusion as foliNIc acid 300 mg IV over 24 hours before switching to 30 mg IV q6h dosing.

filgrastim: Give filgrastim 5 microgram/kg subcutaneously ONCE daily from day 6 until neutrophil recovery.

Cycle 2 - 14 days - R-MV [RITUximab, metHOTREXATe and vinCRISTine]

Cycle length:

RITUximab:

Consider administering corticosteroid premedication before RITUximab if previous doses not well tolerated or if clinically indicated as per institutional practice.
Some centres may choose to use RITUximab 500 mg/m² as per Morris et al 2013.

foliNIc acid:

MUST start 24 hours after start of metHOTREXATe infusion and MUST continue to be administered every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
Some centres can consider using an alternative dosing strategy for certain patients commencing 24 hours after the start of the metHOTREXATe infusion as foliNIc acid 300 mg IV over 24 hours before switching to 30 mg IV q6h dosing.

filgrastim: Give filgrastim 5 microgram/kg subcutaneously ONCE daily from day 6 until neutrophil recovery.

Cycle 3 - 14 days - R-MPV [RITUximab, metHOTREXATe, procarbazine and vinCRISTine]

Cycle length:

RITUximab:

Consider administering corticosteroid premedication before RITUximab if previous doses not well tolerated or if clinically indicated as per institutional practice.
Some centres may choose to use RITUximab 500 mg/m² as per Morris et al 2013.

foliNIc acid:

MUST start 24 hours after start of metHOTREXATe infusion and MUST continue to be administered every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
Some centres can consider using an alternative dosing strategy for certain patients commencing 24 hours after the start of the metHOTREXATe infusion as foliNIc acid 300 mg IV over 24 hours before switching to 30 mg IV q6h dosing.

filgrastim: Give filgrastim 5 microgram/kg subcutaneously ONCE daily from day 6 until neutrophil recovery.

Cycle 4 - 14 days - R-MV [RITUximab, metHOTREXATe and vinCRISTine]

Cycle length:

RITUximab:

Consider administering corticosteroid premedication before RITUximab if previous doses not well tolerated or if clinically indicated as per institutional practice.
Some centres may choose to use RITUximab 500 mg/m² as per Morris et al 2013.

foliNIc acid:

MUST start 24 hours after start of metHOTREXATe infusion and MUST continue to be administered every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
Some centres can consider using an alternative dosing strategy for certain patients commencing 24 hours after the start of the metHOTREXATe infusion as foliNIc acid 300 mg IV over 24 hours before switching to 30 mg IV q6h dosing.

filgrastim: Give filgrastim 5 microgram/kg subcutaneously ONCE daily from day 6 until neutrophil recovery.

Cycle 5 - 14 days - R-MPV [RITUximab, metHOTREXATe, procarbazine and vinCRISTine]

Cycle length:

RITUximab:

Consider administering corticosteroid premedication before RITUximab if previous doses not well tolerated or if clinically indicated as per institutional practice.
Some centres may choose to use RITUximab 500 mg/m² as per Morris et al 2013.

foliNIc acid:

MUST start 24 hours after start of metHOTREXATe infusion and MUST continue to be administered every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
Some centres can consider using an alternative dosing strategy for certain patients commencing 24 hours after the start of the metHOTREXATe infusion as foliNIc acid 300 mg IV over 24 hours before switching to 30 mg IV q6h dosing.

filgrastim: Give filgrastim 5 microgram/kg subcutaneously ONCE daily from day 6 until neutrophil recovery.

Cycle 6 - 14 days - R-MV: If in partial remission after 5 cycles

Cycle length:

RITUximab:

Consider administering corticosteroid premedication before RITUximab if previous doses not well tolerated or if clinically indicated as per institutional practice.
Some centres may choose to use RITUximab 500 mg/m² as per Morris et al 2013.

foliNIc acid:

MUST start 24 hours after start of metHOTREXATe infusion and MUST continue to be administered every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
Some centres can consider using an alternative dosing strategy for certain patients commencing 24 hours after the start of the metHOTREXATe infusion as foliNIc acid 300 mg IV over 24 hours before switching to 30 mg IV q6h dosing.

filgrastim: Give filgrastim 5 microgram/kg subcutaneously ONCE daily from day 6 until neutrophil recovery.

Cycle 7 - 14 days - R-MVP: If in partial remission after 5 cycles

Cycle length:

RITUximab:

Consider administering corticosteroid premedication before RITUximab if previous doses not well tolerated or if clinically indicated as per institutional practice.
Some centres may choose to use RITUximab 500 mg/m² as per Morris et al 2013.

foliNIc acid:

MUST start 24 hours after start of metHOTREXATe infusion and MUST continue to be administered every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
Some centres can consider using an alternative dosing strategy for certain patients commencing 24 hours after the start of the metHOTREXATe infusion as foliNIc acid 300 mg IV over 24 hours before switching to 30 mg IV q6h dosing.

filgrastim: Give filgrastim 5 microgram/kg subcutaneously ONCE daily from day 6 until neutrophil recovery.

Cycle details

Cycle 1 - 14 days - R-MPV [RITUximab (first dose), metHOTREXATe, procarbazine and vinCRISTine]

Medication	Dose	Route	Days	Max Duration
paracetamol *	1000 mg flat dosing	oral administration	1
loratadine *	10 mg	oral administration	1
dexamethasone *	12 mg flat dosing	intravenous	1	15 minutes
RITUximab *	375 mg/m²	intravenous	1	6 hours
procarbazine	100 mg/m² Once daily	oral administration	1 to 7
vinCRISTine	1.4 mg/m² Cap dose per administration at: 2.8 mg	intravenous	2	10 minutes
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4%	125 mL/m²/hour	intravenous	2 to 5
sodium bicarbonate	50 mmol	intravenous	2 to 5
acetazolamide *	250 mg Four times daily	oral administration	2 to 5
metHOTREXATe *	3500 mg/m²	intravenous	2	120 minutes
foliNIc acid (as calcium folinate)	30 mg flat dosing Every six hours	intravenous	3, 4, 5	2 minutes
filgrastim	5 microgram/kg Once daily	subcutaneous injection	6

RITUximab, first dose:

Consider withholding routine anti-hypertensives for 12 hours prior to first RITUximab dose.
For patients at high risk of infusion-related reaction, consider additional pre-medications such as an extra antihistamine dose the day before, an H₂ receptor antagonist and montelukast.
Some centres may choose to use RITUximab 500 mg/m² as per Morris et al 2013.

foliNIc acid:

MUST start 24 hours after start of metHOTREXATe infusion and MUST continue to be administered every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
Some centres can consider using an alternative dosing strategy for certain patients commencing 24 hours after the start of the metHOTREXATe infusion as foliNIc acid 300 mg IV over 24 hours before switching to 30 mg IV q6h dosing.

filgrastim: Give filgrastim 5 microgram/kg subcutaneously ONCE daily from day 6 until neutrophil recovery.

Cycle 2 - 14 days - R-MV [RITUximab, metHOTREXATe and vinCRISTine]

Medication	Dose	Route	Days	Max Duration
paracetamol *	1000 mg flat dosing	oral administration	1
loratadine *	10 mg	oral administration	1
RITUximab *	375 mg/m²	intravenous	1	6 hours
vinCRISTine	1.4 mg/m² Cap dose per administration at: 2.8 mg	intravenous	2	10 minutes
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4%	125 mL/m²/hour	intravenous	2 to 5
sodium bicarbonate	50 mmol	intravenous	2 to 5
acetazolamide *	250 mg Four times daily	oral administration	2 to 5
metHOTREXATe *	3500 mg/m²	intravenous	2	120 minutes
foliNIc acid (as calcium folinate)	30 mg flat dosing Every six hours	intravenous	3, 4, 5	2 minutes
filgrastim	5 microgram/kg Once daily	subcutaneous injection	6

RITUximab:

Consider administering corticosteroid premedication before RITUximab if previous doses not well tolerated or if clinically indicated as per institutional practice.
Some centres may choose to use RITUximab 500 mg/m² as per Morris et al 2013.

foliNIc acid:

MUST start 24 hours after start of metHOTREXATe infusion and MUST continue to be administered every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
Some centres can consider using an alternative dosing strategy for certain patients commencing 24 hours after the start of the metHOTREXATe infusion as foliNIc acid 300 mg IV over 24 hours before switching to 30 mg IV q6h dosing.

filgrastim: Give filgrastim 5 microgram/kg subcutaneously ONCE daily from day 6 until neutrophil recovery.

Cycle 3 - 14 days - R-MPV [RITUximab, metHOTREXATe, procarbazine and vinCRISTine]

Medication	Dose	Route	Days	Max Duration
paracetamol *	1000 mg flat dosing	oral administration	1
loratadine *	10 mg	oral administration	1
RITUximab *	375 mg/m²	intravenous	1	6 hours
procarbazine	100 mg/m² Once daily	oral administration	1 to 7
vinCRISTine	1.4 mg/m² Cap dose per administration at: 2.8 mg	intravenous	2	10 minutes
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4%	125 mL/m²/hour	intravenous	2 to 5
sodium bicarbonate	50 mmol	intravenous	2 to 5
acetazolamide *	250 mg Four times daily	oral administration	2 to 5
metHOTREXATe *	3500 mg/m²	intravenous	2	120 minutes
foliNIc acid (as calcium folinate)	30 mg flat dosing Every six hours	intravenous	3, 4, 5	2 minutes
filgrastim	5 microgram/kg Once daily	subcutaneous injection	6

RITUximab:

Consider administering corticosteroid premedication before RITUximab if previous doses not well tolerated or if clinically indicated as per institutional practice.
Some centres may choose to use RITUximab 500 mg/m² as per Morris et al 2013.

foliNIc acid:

MUST start 24 hours after start of metHOTREXATe infusion and MUST continue to be administered every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
Some centres can consider using an alternative dosing strategy for certain patients commencing 24 hours after the start of the metHOTREXATe infusion as foliNIc acid 300 mg IV over 24 hours before switching to 30 mg IV q6h dosing.

filgrastim: Give filgrastim 5 microgram/kg subcutaneously ONCE daily from day 6 until neutrophil recovery.

Cycle 4 - 14 days - R-MV [RITUximab, metHOTREXATe and vinCRISTine]

Medication	Dose	Route	Days	Max Duration
paracetamol *	1000 mg flat dosing	oral administration	1
loratadine *	10 mg	oral administration	1
RITUximab *	375 mg/m²	intravenous	1	6 hours
vinCRISTine	1.4 mg/m² Cap dose per administration at: 2.8 mg	intravenous	2	10 minutes
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4%	125 mL/m²/hour	intravenous	2 to 5
sodium bicarbonate	50 mmol	intravenous	2 to 5
acetazolamide *	250 mg Four times daily	oral administration	2 to 5
metHOTREXATe *	3500 mg/m²	intravenous	2	120 minutes
foliNIc acid (as calcium folinate)	30 mg flat dosing Every six hours	intravenous	3, 4, 5	2 minutes
filgrastim	5 microgram/kg Once daily	subcutaneous injection	6

RITUximab:

Consider administering corticosteroid premedication before RITUximab if previous doses not well tolerated or if clinically indicated as per institutional practice.
Some centres may choose to use RITUximab 500 mg/m² as per Morris et al 2013.

foliNIc acid:

MUST start 24 hours after start of metHOTREXATe infusion and MUST continue to be administered every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
Some centres can consider using an alternative dosing strategy for certain patients commencing 24 hours after the start of the metHOTREXATe infusion as foliNIc acid 300 mg IV over 24 hours before switching to 30 mg IV q6h dosing.

filgrastim: Give filgrastim 5 microgram/kg subcutaneously ONCE daily from day 6 until neutrophil recovery.

Cycle 5 - 14 days - R-MPV [RITUximab, metHOTREXATe, procarbazine and vinCRISTine]

Medication	Dose	Route	Days	Max Duration
paracetamol *	1000 mg flat dosing	oral administration	1
loratadine *	10 mg	oral administration	1
RITUximab *	375 mg/m²	intravenous	1	6 hours
procarbazine	100 mg/m² Once daily	oral administration	1 to 7
vinCRISTine	1.4 mg/m² Cap dose per administration at: 2.8 mg	intravenous	2	10 minutes
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4%	125 mL/m²/hour	intravenous	2 to 5
sodium bicarbonate	50 mmol	intravenous	2 to 5
acetazolamide *	250 mg Four times daily	oral administration	2 to 5
metHOTREXATe *	3500 mg/m²	intravenous	2	120 minutes
foliNIc acid (as calcium folinate)	30 mg flat dosing Every six hours	intravenous	3, 4, 5	2 minutes
filgrastim	5 microgram/kg Once daily	subcutaneous injection	6

RITUximab:

Consider administering corticosteroid premedication before RITUximab if previous doses not well tolerated or if clinically indicated as per institutional practice.
Some centres may choose to use RITUximab 500 mg/m² as per Morris et al 2013.

foliNIc acid:

MUST start 24 hours after start of metHOTREXATe infusion and MUST continue to be administered every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
Some centres can consider using an alternative dosing strategy for certain patients commencing 24 hours after the start of the metHOTREXATe infusion as foliNIc acid 300 mg IV over 24 hours before switching to 30 mg IV q6h dosing.

filgrastim: Give filgrastim 5 microgram/kg subcutaneously ONCE daily from day 6 until neutrophil recovery.

Cycle 6 - 14 days - R-MV: If in partial remission after 5 cycles

Medication	Dose	Route	Days	Max Duration
paracetamol *	1000 mg flat dosing	oral administration	1
loratadine *	10 mg	oral administration	1
RITUximab *	375 mg/m²	intravenous	1	6 hours
vinCRISTine	1.4 mg/m² Cap dose per administration at: 2.8 mg	intravenous	2	10 minutes
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4%	125 mL/m²/hour	intravenous	2 to 5
sodium bicarbonate	50 mmol	intravenous	2 to 5
acetazolamide *	250 mg Four times daily	oral administration	2 to 5
metHOTREXATe *	3500 mg/m²	intravenous	2	120 minutes
foliNIc acid (as calcium folinate)	30 mg flat dosing Every six hours	intravenous	3, 4, 5	2 minutes
filgrastim	5 microgram/kg Once daily	subcutaneous injection	6

RITUximab:

Consider administering corticosteroid premedication before RITUximab if previous doses not well tolerated or if clinically indicated as per institutional practice.
Some centres may choose to use RITUximab 500 mg/m² as per Morris et al 2013.

foliNIc acid:

MUST start 24 hours after start of metHOTREXATe infusion and MUST continue to be administered every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
Some centres can consider using an alternative dosing strategy for certain patients commencing 24 hours after the start of the metHOTREXATe infusion as foliNIc acid 300 mg IV over 24 hours before switching to 30 mg IV q6h dosing.

filgrastim: Give filgrastim 5 microgram/kg subcutaneously ONCE daily from day 6 until neutrophil recovery.

Cycle 7 - 14 days - R-MVP: If in partial remission after 5 cycles

Medication	Dose	Route	Days	Max Duration
paracetamol *	1000 mg flat dosing	oral administration	1
loratadine *	10 mg	oral administration	1
RITUximab *	375 mg/m²	intravenous	1	6 hours
procarbazine	100 mg/m² Once daily	oral administration	1 to 7
vinCRISTine	1.4 mg/m² Cap dose per administration at: 2.8 mg	intravenous	2	10 minutes
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4%	125 mL/m²/hour	intravenous	2 to 5
sodium bicarbonate	50 mmol	intravenous	2 to 5
acetazolamide *	250 mg Four times daily	oral administration	2 to 5
metHOTREXATe *	3500 mg/m²	intravenous	2	120 minutes
foliNIc acid (as calcium folinate)	30 mg flat dosing Every six hours	intravenous	3, 4, 5	2 minutes
filgrastim	5 microgram/kg Once daily	subcutaneous injection	6

RITUximab:

Consider administering corticosteroid premedication before RITUximab if previous doses not well tolerated or if clinically indicated as per institutional practice.
Some centres may choose to use RITUximab 500 mg/m² as per Morris et al 2013.

foliNIc acid:

MUST start 24 hours after start of metHOTREXATe infusion and MUST continue to be administered every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
Some centres can consider using an alternative dosing strategy for certain patients commencing 24 hours after the start of the metHOTREXATe infusion as foliNIc acid 300 mg IV over 24 hours before switching to 30 mg IV q6h dosing.

filgrastim: Give filgrastim 5 microgram/kg subcutaneously ONCE daily from day 6 until neutrophil recovery.

Full details

Cycle 1 - 14 days - R-MPV [RITUximab (first dose), metHOTREXATe, procarbazine and vinCRISTine]

Day: 1

Medication	Dose	Route	Max duration	Details
paracetamol *	1000 mg flat dosing	oral administration		Instructions: 30 to 60 minutes prior to RITUximab.
loratadine *	10 mg	oral administration		Instructions: 30 to 60 minutes prior to RITUximab.
dexamethasone *	12 mg flat dosing	intravenous	15 minutes	Instructions: 30 to 60 minutes prior to RITUximab, or as per institutional practice.
RITUximab *	375 mg/m²	intravenous	6 hours	Instructions: Consider withholding routine anti-hypertensives for 12 hours prior to first RITUximab dose. For patients at high risk of infusion-related reaction, consider additional pre-medications such as an extra antihistamine dose the day before, an H₂receptor antagonist and montelukast. Start infusion at 50 mg/hour. If tolerated, rate can be increased by 50 mg/hour every 30 minutes to a maximum rate of 400 mg/hour.
procarbazine	100 mg/m² Once daily	oral administration		Instructions: Take at night with food. Do not drink alcohol and avoid large amounts of tyramine-rich foods (e.g. aged cheeses, cured meats, fermented foods and yeast extracts such as Marmite®) while being treated with this medicine. Talk to your doctor or pharmacist before taking medicines purchased over the counter from a pharmacy, supermarket or health food store. Round dose to closest multiple of 50 mg capsules.

Day: 2

Medication	Dose	Route	Max duration	Details
procarbazine	100 mg/m² Once daily	oral administration		Instructions: Take at night with food. Do not drink alcohol and avoid large amounts of tyramine-rich foods (e.g. aged cheeses, cured meats, fermented foods and yeast extracts such as Marmite®) while being treated with this medicine. Talk to your doctor or pharmacist before taking medicines purchased over the counter from a pharmacy, supermarket or health food store. Round dose to closest multiple of 50 mg capsules.
vinCRISTine	1.4 mg/m² Cap dose per administration at: 2.8 mg	intravenous	10 minutes	Instructions: Diluted in a minibag. FOR INTRAVENOUS USE ONLY – fatal if given by any other routes. Warning vesicant—ensure vein is patent prior to administration, administer vesicant as per institutional policy and monitor for signs of extravasation throughout administration.
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4%	125 mL/m²/hour	intravenous		Instructions: To each 1000 mL bag admix 50 mmol sodium bicarbonate. Or an alternative alkalinized intravenous infusion may be used as per institutional practice. Commence at least 6 hours prior to metHOTREXATe infusion and run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate	50 mmol	intravenous		Instructions: Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%. Dose of sodium bicarbonate is approximately 6 mmol/m²/hour when admixed bag is infused at 125 mL/m²/hour.
acetazolamide *	250 mg Four times daily	oral administration		Instructions: When required. Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1µmol/L (level as per institutional practice).
metHOTREXATe *	3500 mg/m²	intravenous	120 minutes

Day: 3

Medication	Dose	Route	Max duration	Details
procarbazine	100 mg/m² Once daily	oral administration		Instructions: Take at night with food. Do not drink alcohol and avoid large amounts of tyramine-rich foods (e.g. aged cheeses, cured meats, fermented foods and yeast extracts such as Marmite®) while being treated with this medicine. Talk to your doctor or pharmacist before taking medicines purchased over the counter from a pharmacy, supermarket or health food store. Round dose to closest multiple of 50 mg capsules.
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4%	125 mL/m²/hour	intravenous		Instructions: To each 1000 mL bag admix 50 mmol sodium bicarbonate. Or an alternative alkalinized intravenous infusion may be used as per institutional practice. Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate	50 mmol	intravenous		Instructions: Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%. Dose of sodium bicarbonate is approximately 6 mmol/m²/hour when admixed bag is infused at 125 mL/m²/hour.
acetazolamide *	250 mg Four times daily	oral administration		Instructions: When required. Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1µmol/L (level as per institutional practice).
foliNIc acid (as calcium folinate)	30 mg flat dosing Every six hours	intravenous	2 minutes	Instructions: Starting 24 hours after start of metHOTREXATe infusion and continue to administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice). If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information.

Day: 4

Medication	Dose	Route	Max duration	Details
procarbazine	100 mg/m² Once daily	oral administration		Instructions: Take at night with food. Do not drink alcohol and avoid large amounts of tyramine-rich foods (e.g. aged cheeses, cured meats, fermented foods and yeast extracts such as Marmite®) while being treated with this medicine. Talk to your doctor or pharmacist before taking medicines purchased over the counter from a pharmacy, supermarket or health food store. Round dose to closest multiple of 50 mg capsules.
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4%	125 mL/m²/hour	intravenous		Instructions: To each 1000 mL bag admix 50 mmol sodium bicarbonate. Or an alternative alkalinized intravenous infusion may be used as per institutional practice. Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate	50 mmol	intravenous		Instructions: Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%. Dose of sodium bicarbonate is approximately 6 mmol/m²/hour when admixed bag is infused at 125 mL/m²/hour.
acetazolamide *	250 mg Four times daily	oral administration		Instructions: When required. Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1µmol/L (level as per institutional practice).
foliNIc acid (as calcium folinate)	30 mg flat dosing Every six hours	intravenous	2 minutes	Instructions: Administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice). If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information.

Day: 5

Medication	Dose	Route	Max duration	Details
procarbazine	100 mg/m² Once daily	oral administration		Instructions: Take at night with food. Do not drink alcohol and avoid large amounts of tyramine-rich foods (e.g. aged cheeses, cured meats, fermented foods and yeast extracts such as Marmite®) while being treated with this medicine. Talk to your doctor or pharmacist before taking medicines purchased over the counter from a pharmacy, supermarket or health food store. Round dose to closest multiple of 50 mg capsules.
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4%	125 mL/m²/hour	intravenous		Instructions: To each 1000 mL bag admix 50 mmol sodium bicarbonate. Or an alternative alkalinized intravenous infusion may be used as per institutional practice. Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice). Administration may continue past Day 5 if metHOTREXATe level is still elevated.
sodium bicarbonate	50 mmol	intravenous		Instructions: Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%. Dose of sodium bicarbonate is approximately 6 mmol/m²/hour when admixed bag is infused at 125 mL/m²/hour. Administration may continue past Day 5 if metHOTREXATe level is still elevated.
acetazolamide *	250 mg Four times daily	oral administration		Instructions: When required. Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice). Administration may continue past Day 5 if metHOTREXATe level is still elevated.
foliNIc acid (as calcium folinate)	30 mg flat dosing Every six hours	intravenous	2 minutes	Instructions: Administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice). If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information. Administration may continue past Day 5 if metHOTREXATe level is still elevated.

Day: 6

Medication	Dose	Route	Max duration	Details
procarbazine	100 mg/m² Once daily	oral administration		Instructions: Take at night with food. Do not drink alcohol and avoid large amounts of tyramine-rich foods (e.g. aged cheeses, cured meats, fermented foods and yeast extracts such as Marmite®) while being treated with this medicine. Talk to your doctor or pharmacist before taking medicines purchased over the counter from a pharmacy, supermarket or health food store. Round dose to closest multiple of 50 mg capsules.
filgrastim	5 microgram/kg Once daily	subcutaneous injection		Instructions: Give ONCE daily from Day 6 until neutrophil recovery. Round dose to nearest prefilled syringe dose of 300 micrograms or 480 micrograms.

Day: 7

Medication	Dose	Route	Max duration	Details
procarbazine	100 mg/m² Once daily	oral administration		Instructions: Take at night with food. Do not drink alcohol and avoid large amounts of tyramine-rich foods (e.g. aged cheeses, cured meats, fermented foods and yeast extracts such as Marmite®) while being treated with this medicine. Talk to your doctor or pharmacist before taking medicines purchased over the counter from a pharmacy, supermarket or health food store. Round dose to closest multiple of 50 mg capsules.

Cycle 2 - 14 days - R-MV [RITUximab, metHOTREXATe and vinCRISTine]

Day: 1

Medication	Dose	Route	Max duration	Details
paracetamol *	1000 mg flat dosing	oral administration		Instructions: 30 to 60 minutes prior to RITUximab.
loratadine *	10 mg	oral administration		Instructions: 30 to 60 minutes prior to RITUximab.
RITUximab *	375 mg/m²	intravenous	6 hours	Instructions: Consider administering corticosteroid premedication if previous doses not well tolerated or if clinically indicated, as per institutional practice. Start infusion at 100 mg/hour. If tolerated, rate can be increased by 100 mg/hour every 30 minutes to a maximum rate of 400 mg/hour, or as per institutional practice.

Day: 2

Medication	Dose	Route	Max duration	Details
vinCRISTine	1.4 mg/m² Cap dose per administration at: 2.8 mg	intravenous	10 minutes	Instructions: Diluted in a minibag. FOR INTRAVENOUS USE ONLY – fatal if given by any other routes. Warning vesicant—ensure vein is patent prior to administration, administer vesicant as per institutional policy and monitor for signs of extravasation throughout administration.
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4%	125 mL/m²/hour	intravenous		Instructions: To each 1000 mL bag admix 50 mmol sodium bicarbonate. Or an alternative alkalinized intravenous infusion may be used as per institutional practice. Commence at least 6 hours prior to metHOTREXATe infusion and run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate	50 mmol	intravenous		Instructions: Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%. Dose of sodium bicarbonate is approximately 6 mmol/m²/hour when admixed bag is infused at 125 mL/m²/hour.
acetazolamide *	250 mg Four times daily	oral administration		Instructions: When required. Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1µmol/L (level as per institutional practice).
metHOTREXATe *	3500 mg/m²	intravenous	120 minutes

Day: 3

Medication	Dose	Route	Max duration	Details
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4%	125 mL/m²/hour	intravenous		Instructions: To each 1000 mL bag admix 50 mmol sodium bicarbonate. Or an alternative alkalinized intravenous infusion may be used as per institutional practice. Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate	50 mmol	intravenous		Instructions: Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%. Dose of sodium bicarbonate is approximately 6 mmol/m²/hour when admixed bag is infused at 125 mL/m²/hour.
acetazolamide *	250 mg Four times daily	oral administration		Instructions: When required. Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1µmol/L (level as per institutional practice).
foliNIc acid (as calcium folinate)	30 mg flat dosing Every six hours	intravenous	2 minutes	Instructions: Starting 24 hours after start of metHOTREXATe infusion and continue to administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice). If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information.

Day: 4

Medication	Dose	Route	Max duration	Details
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4%	125 mL/m²/hour	intravenous		Instructions: To each 1000 mL bag admix 50 mmol sodium bicarbonate. Or an alternative alkalinized intravenous infusion may be used as per institutional practice. Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate	50 mmol	intravenous		Instructions: Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%. Dose of sodium bicarbonate is approximately 6 mmol/m²/hour when admixed bag is infused at 125 mL/m²/hour.
acetazolamide *	250 mg Four times daily	oral administration		Instructions: When required. Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1µmol/L (level as per institutional practice).
foliNIc acid (as calcium folinate)	30 mg flat dosing Every six hours	intravenous	2 minutes	Instructions: Administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice). If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information.

Day: 5

Medication	Dose	Route	Max duration	Details
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4%	125 mL/m²/hour	intravenous		Instructions: To each 1000 mL bag admix 50 mmol sodium bicarbonate. Or an alternative alkalinized intravenous infusion may be used as per institutional practice. Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice). Administration may continue past Day 5 if metHOTREXATe level is still elevated.
sodium bicarbonate	50 mmol	intravenous		Instructions: Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%. Dose of sodium bicarbonate is approximately 6 mmol/m²/hour when admixed bag is infused at 125 mL/m²/hour. Administration may continue past Day 5 if metHOTREXATe level is still elevated.
acetazolamide *	250 mg Four times daily	oral administration		Instructions: When required. Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice). Administration may continue past Day 5 if metHOTREXATe level is still elevated.
foliNIc acid (as calcium folinate)	30 mg flat dosing Every six hours	intravenous	2 minutes	Instructions: Administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice). If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information. Administration may continue past Day 5 if metHOTREXATe level is still elevated.

Day: 6

Medication	Dose	Route	Max duration	Details
filgrastim	5 microgram/kg Once daily	subcutaneous injection		Instructions: Give ONCE daily from Day 6 until neutrophil recovery. Round dose to nearest prefilled syringe dose of 300 micrograms or 480 micrograms.

Cycle 3 - 14 days - R-MPV [RITUximab, metHOTREXATe, procarbazine and vinCRISTine]

Day: 1

Medication	Dose	Route	Max duration	Details
paracetamol *	1000 mg flat dosing	oral administration		Instructions: 30 to 60 minutes prior to RITUximab.
loratadine *	10 mg	oral administration		Instructions: 30 to 60 minutes prior to RITUximab.
RITUximab *	375 mg/m²	intravenous	6 hours	Instructions: Consider administering corticosteroid premedication if previous doses not well tolerated or if clinically indicated, as per institutional practice. Start infusion at 100 mg/hour. If tolerated, rate can be increased by 100 mg/hour every 30 minutes to a maximum rate of 400 mg/hour, or as per institutional practice.
procarbazine	100 mg/m² Once daily	oral administration		Instructions: Take at night with food. Do not drink alcohol and avoid large amounts of tyramine-rich foods (e.g. aged cheeses, cured meats, fermented foods and yeast extracts such as Marmite®) while being treated with this medicine. Talk to your doctor or pharmacist before taking medicines purchased over the counter from a pharmacy, supermarket or health food store. Round dose to closest multiple of 50 mg capsules.

Day: 2

Medication	Dose	Route	Max duration	Details
procarbazine	100 mg/m² Once daily	oral administration		Instructions: Take at night with food. Do not drink alcohol and avoid large amounts of tyramine-rich foods (e.g. aged cheeses, cured meats, fermented foods and yeast extracts such as Marmite®) while being treated with this medicine. Talk to your doctor or pharmacist before taking medicines purchased over the counter from a pharmacy, supermarket or health food store. Round dose to closest multiple of 50 mg capsules.
vinCRISTine	1.4 mg/m² Cap dose per administration at: 2.8 mg	intravenous	10 minutes	Instructions: Diluted in a minibag. FOR INTRAVENOUS USE ONLY – fatal if given by any other routes. Warning vesicant—ensure vein is patent prior to administration, administer vesicant as per institutional policy and monitor for signs of extravasation throughout administration.
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4%	125 mL/m²/hour	intravenous		Instructions: To each 1000 mL bag admix 50 mmol sodium bicarbonate. Or an alternative alkalinized intravenous infusion may be used as per institutional practice. Commence at least 6 hours prior to metHOTREXATe infusion and run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate	50 mmol	intravenous		Instructions: Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%. Dose of sodium bicarbonate is approximately 6 mmol/m²/hour when admixed bag is infused at 125 mL/m²/hour.
acetazolamide *	250 mg Four times daily	oral administration		Instructions: When required. Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1µmol/L (level as per institutional practice).
metHOTREXATe *	3500 mg/m²	intravenous	120 minutes

Day: 3

Medication	Dose	Route	Max duration	Details
procarbazine	100 mg/m² Once daily	oral administration		Instructions: Take at night with food. Do not drink alcohol and avoid large amounts of tyramine-rich foods (e.g. aged cheeses, cured meats, fermented foods and yeast extracts such as Marmite®) while being treated with this medicine. Talk to your doctor or pharmacist before taking medicines purchased over the counter from a pharmacy, supermarket or health food store. Round dose to closest multiple of 50 mg capsules.
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4%	125 mL/m²/hour	intravenous		Instructions: To each 1000 mL bag admix 50 mmol sodium bicarbonate. Or an alternative alkalinized intravenous infusion may be used as per institutional practice. Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate	50 mmol	intravenous		Instructions: Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%. Dose of sodium bicarbonate is approximately 6 mmol/m²/hour when admixed bag is infused at 125 mL/m²/hour.
acetazolamide *	250 mg Four times daily	oral administration		Instructions: When required. Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1µmol/L (level as per institutional practice).
foliNIc acid (as calcium folinate)	30 mg flat dosing Every six hours	intravenous	2 minutes	Instructions: Starting 24 hours after start of metHOTREXATe infusion and continue to administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice). If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information.

Day: 4

Medication	Dose	Route	Max duration	Details
procarbazine	100 mg/m² Once daily	oral administration		Instructions: Take at night with food. Do not drink alcohol and avoid large amounts of tyramine-rich foods (e.g. aged cheeses, cured meats, fermented foods and yeast extracts such as Marmite®) while being treated with this medicine. Talk to your doctor or pharmacist before taking medicines purchased over the counter from a pharmacy, supermarket or health food store. Round dose to closest multiple of 50 mg capsules.
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4%	125 mL/m²/hour	intravenous		Instructions: To each 1000 mL bag admix 50 mmol sodium bicarbonate. Or an alternative alkalinized intravenous infusion may be used as per institutional practice. Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate	50 mmol	intravenous		Instructions: Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%. Dose of sodium bicarbonate is approximately 6 mmol/m²/hour when admixed bag is infused at 125 mL/m²/hour.
acetazolamide *	250 mg Four times daily	oral administration		Instructions: When required. Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1µmol/L (level as per institutional practice).
foliNIc acid (as calcium folinate)	30 mg flat dosing Every six hours	intravenous	2 minutes	Instructions: Administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice). If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information.

Day: 5

Medication	Dose	Route	Max duration	Details
procarbazine	100 mg/m² Once daily	oral administration		Instructions: Take at night with food. Do not drink alcohol and avoid large amounts of tyramine-rich foods (e.g. aged cheeses, cured meats, fermented foods and yeast extracts such as Marmite®) while being treated with this medicine. Talk to your doctor or pharmacist before taking medicines purchased over the counter from a pharmacy, supermarket or health food store. Round dose to closest multiple of 50 mg capsules.
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4%	125 mL/m²/hour	intravenous		Instructions: To each 1000 mL bag admix 50 mmol sodium bicarbonate. Or an alternative alkalinized intravenous infusion may be used as per institutional practice. Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice). Administration may continue past Day 5 if metHOTREXATe level is still elevated.
sodium bicarbonate	50 mmol	intravenous		Instructions: Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%. Dose of sodium bicarbonate is approximately 6 mmol/m²/hour when admixed bag is infused at 125 mL/m²/hour. Administration may continue past Day 5 if metHOTREXATe level is still elevated.
acetazolamide *	250 mg Four times daily	oral administration		Instructions: When required. Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice). Administration may continue past Day 5 if metHOTREXATe level is still elevated.
foliNIc acid (as calcium folinate)	30 mg flat dosing Every six hours	intravenous	2 minutes	Instructions: Administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice). If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information. Administration may continue past Day 5 if metHOTREXATe level is still elevated.

Day: 6

Medication	Dose	Route	Max duration	Details
procarbazine	100 mg/m² Once daily	oral administration		Instructions: Take at night with food. Do not drink alcohol and avoid large amounts of tyramine-rich foods (e.g. aged cheeses, cured meats, fermented foods and yeast extracts such as Marmite®) while being treated with this medicine. Talk to your doctor or pharmacist before taking medicines purchased over the counter from a pharmacy, supermarket or health food store. Round dose to closest multiple of 50 mg capsules.
filgrastim	5 microgram/kg Once daily	subcutaneous injection		Instructions: Give ONCE daily from Day 6 until neutrophil recovery. Round dose to nearest prefilled syringe dose of 300 micrograms or 480 micrograms.

Day: 7

Medication	Dose	Route	Max duration	Details
procarbazine	100 mg/m² Once daily	oral administration		Instructions: Take at night with food. Do not drink alcohol and avoid large amounts of tyramine-rich foods (e.g. aged cheeses, cured meats, fermented foods and yeast extracts such as Marmite®) while being treated with this medicine. Talk to your doctor or pharmacist before taking medicines purchased over the counter from a pharmacy, supermarket or health food store. Round dose to closest multiple of 50 mg capsules.

Cycle 4 - 14 days - R-MV [RITUximab, metHOTREXATe and vinCRISTine]

Day: 1

Medication	Dose	Route	Max duration	Details
paracetamol *	1000 mg flat dosing	oral administration		Instructions: 30 to 60 minutes prior to RITUximab.
loratadine *	10 mg	oral administration		Instructions: 30 to 60 minutes prior to RITUximab.
RITUximab *	375 mg/m²	intravenous	6 hours	Instructions: Consider administering corticosteroid premedication if previous doses not well tolerated or if clinically indicated, as per institutional practice. Start infusion at 100 mg/hour. If tolerated, rate can be increased by 100 mg/hour every 30 minutes to a maximum rate of 400 mg/hour, or as per institutional practice.

Day: 2

Medication	Dose	Route	Max duration	Details
vinCRISTine	1.4 mg/m² Cap dose per administration at: 2.8 mg	intravenous	10 minutes	Instructions: Diluted in a minibag. FOR INTRAVENOUS USE ONLY – fatal if given by any other routes. Warning vesicant—ensure vein is patent prior to administration, administer vesicant as per institutional policy and monitor for signs of extravasation throughout administration.
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4%	125 mL/m²/hour	intravenous		Instructions: To each 1000 mL bag admix 50 mmol sodium bicarbonate. Or an alternative alkalinized intravenous infusion may be used as per institutional practice. Commence at least 6 hours prior to metHOTREXATe infusion and run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate	50 mmol	intravenous		Instructions: Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%. Dose of sodium bicarbonate is approximately 6 mmol/m²/hour when admixed bag is infused at 125 mL/m²/hour.
acetazolamide *	250 mg Four times daily	oral administration		Instructions: When required. Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1µmol/L (level as per institutional practice).
metHOTREXATe *	3500 mg/m²	intravenous	120 minutes

Day: 3

Medication	Dose	Route	Max duration	Details
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4%	125 mL/m²/hour	intravenous		Instructions: To each 1000 mL bag admix 50 mmol sodium bicarbonate. Or an alternative alkalinized intravenous infusion may be used as per institutional practice. Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate	50 mmol	intravenous		Instructions: Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%. Dose of sodium bicarbonate is approximately 6 mmol/m²/hour when admixed bag is infused at 125 mL/m²/hour.
acetazolamide *	250 mg Four times daily	oral administration		Instructions: When required. Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1µmol/L (level as per institutional practice).
foliNIc acid (as calcium folinate)	30 mg flat dosing Every six hours	intravenous	2 minutes	Instructions: Starting 24 hours after start of metHOTREXATe infusion and continue to administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice). If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information.

Day: 4

Medication	Dose	Route	Max duration	Details
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4%	125 mL/m²/hour	intravenous		Instructions: To each 1000 mL bag admix 50 mmol sodium bicarbonate. Or an alternative alkalinized intravenous infusion may be used as per institutional practice. Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate	50 mmol	intravenous		Instructions: Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%. Dose of sodium bicarbonate is approximately 6 mmol/m²/hour when admixed bag is infused at 125 mL/m²/hour.
acetazolamide *	250 mg Four times daily	oral administration		Instructions: When required. Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1µmol/L (level as per institutional practice).
foliNIc acid (as calcium folinate)	30 mg flat dosing Every six hours	intravenous	2 minutes	Instructions: Administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice). If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information.

Day: 5

Medication	Dose	Route	Max duration	Details
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4%	125 mL/m²/hour	intravenous		Instructions: To each 1000 mL bag admix 50 mmol sodium bicarbonate. Or an alternative alkalinized intravenous infusion may be used as per institutional practice. Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice). Administration may continue past Day 5 if metHOTREXATe level is still elevated.
sodium bicarbonate	50 mmol	intravenous		Instructions: Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%. Dose of sodium bicarbonate is approximately 6 mmol/m²/hour when admixed bag is infused at 125 mL/m²/hour. Administration may continue past Day 5 if metHOTREXATe level is still elevated.
acetazolamide *	250 mg Four times daily	oral administration		Instructions: When required. Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice). Administration may continue past Day 5 if metHOTREXATe level is still elevated.
foliNIc acid (as calcium folinate)	30 mg flat dosing Every six hours	intravenous	2 minutes	Instructions: Administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice). If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information. Administration may continue past Day 5 if metHOTREXATe level is still elevated.

Day: 6

Medication	Dose	Route	Max duration	Details
filgrastim	5 microgram/kg Once daily	subcutaneous injection		Instructions: Give ONCE daily from Day 6 until neutrophil recovery. Round dose to nearest prefilled syringe dose of 300 micrograms or 480 micrograms.

Cycle 5 - 14 days - R-MPV [RITUximab, metHOTREXATe, procarbazine and vinCRISTine]

Day: 1

Medication	Dose	Route	Max duration	Details
paracetamol *	1000 mg flat dosing	oral administration		Instructions: 30 to 60 minutes prior to RITUximab.
loratadine *	10 mg	oral administration		Instructions: 30 to 60 minutes prior to RITUximab.
RITUximab *	375 mg/m²	intravenous	6 hours	Instructions: Consider administering corticosteroid premedication if previous doses not well tolerated or if clinically indicated, as per institutional practice. Start infusion at 100 mg/hour. If tolerated, rate can be increased by 100 mg/hour every 30 minutes to a maximum rate of 400 mg/hour, or as per institutional practice.
procarbazine	100 mg/m² Once daily	oral administration		Instructions: Take at night with food. Do not drink alcohol and avoid large amounts of tyramine-rich foods (e.g. aged cheeses, cured meats, fermented foods and yeast extracts such as Marmite®) while being treated with this medicine. Talk to your doctor or pharmacist before taking medicines purchased over the counter from a pharmacy, supermarket or health food store. Round dose to closest multiple of 50 mg capsules.

Day: 2

Medication	Dose	Route	Max duration	Details
procarbazine	100 mg/m² Once daily	oral administration		Instructions: Take at night with food. Do not drink alcohol and avoid large amounts of tyramine-rich foods (e.g. aged cheeses, cured meats, fermented foods and yeast extracts such as Marmite®) while being treated with this medicine. Talk to your doctor or pharmacist before taking medicines purchased over the counter from a pharmacy, supermarket or health food store. Round dose to closest multiple of 50 mg capsules.
vinCRISTine	1.4 mg/m² Cap dose per administration at: 2.8 mg	intravenous	10 minutes	Instructions: Diluted in a minibag. FOR INTRAVENOUS USE ONLY – fatal if given by any other routes. Warning vesicant—ensure vein is patent prior to administration, administer vesicant as per institutional policy and monitor for signs of extravasation throughout administration.
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4%	125 mL/m²/hour	intravenous		Instructions: To each 1000 mL bag admix 50 mmol sodium bicarbonate. Or an alternative alkalinized intravenous infusion may be used as per institutional practice. Commence at least 6 hours prior to metHOTREXATe infusion and run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate	50 mmol	intravenous		Instructions: Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%. Dose of sodium bicarbonate is approximately 6 mmol/m²/hour when admixed bag is infused at 125 mL/m²/hour.
acetazolamide *	250 mg Four times daily	oral administration		Instructions: When required. Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1µmol/L (level as per institutional practice).
metHOTREXATe *	3500 mg/m²	intravenous	120 minutes

Day: 3

Medication	Dose	Route	Max duration	Details
procarbazine	100 mg/m² Once daily	oral administration		Instructions: Take at night with food. Do not drink alcohol and avoid large amounts of tyramine-rich foods (e.g. aged cheeses, cured meats, fermented foods and yeast extracts such as Marmite®) while being treated with this medicine. Talk to your doctor or pharmacist before taking medicines purchased over the counter from a pharmacy, supermarket or health food store. Round dose to closest multiple of 50 mg capsules.
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4%	125 mL/m²/hour	intravenous		Instructions: To each 1000 mL bag admix 50 mmol sodium bicarbonate. Or an alternative alkalinized intravenous infusion may be used as per institutional practice. Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate	50 mmol	intravenous		Instructions: Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%. Dose of sodium bicarbonate is approximately 6 mmol/m²/hour when admixed bag is infused at 125 mL/m²/hour.
acetazolamide *	250 mg Four times daily	oral administration		Instructions: When required. Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1µmol/L (level as per institutional practice).
foliNIc acid (as calcium folinate)	30 mg flat dosing Every six hours	intravenous	2 minutes	Instructions: Starting 24 hours after start of metHOTREXATe infusion and continue to administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice). If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information.

Day: 4

Medication	Dose	Route	Max duration	Details
procarbazine	100 mg/m² Once daily	oral administration		Instructions: Take at night with food. Do not drink alcohol and avoid large amounts of tyramine-rich foods (e.g. aged cheeses, cured meats, fermented foods and yeast extracts such as Marmite®) while being treated with this medicine. Talk to your doctor or pharmacist before taking medicines purchased over the counter from a pharmacy, supermarket or health food store. Round dose to closest multiple of 50 mg capsules.
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4%	125 mL/m²/hour	intravenous		Instructions: To each 1000 mL bag admix 50 mmol sodium bicarbonate. Or an alternative alkalinized intravenous infusion may be used as per institutional practice. Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate	50 mmol	intravenous		Instructions: Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%. Dose of sodium bicarbonate is approximately 6 mmol/m²/hour when admixed bag is infused at 125 mL/m²/hour.
acetazolamide *	250 mg Four times daily	oral administration		Instructions: When required. Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1µmol/L (level as per institutional practice).
foliNIc acid (as calcium folinate)	30 mg flat dosing Every six hours	intravenous	2 minutes	Instructions: Administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice). If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information.

Day: 5

Medication	Dose	Route	Max duration	Details
procarbazine	100 mg/m² Once daily	oral administration		Instructions: Take at night with food. Do not drink alcohol and avoid large amounts of tyramine-rich foods (e.g. aged cheeses, cured meats, fermented foods and yeast extracts such as Marmite®) while being treated with this medicine. Talk to your doctor or pharmacist before taking medicines purchased over the counter from a pharmacy, supermarket or health food store. Round dose to closest multiple of 50 mg capsules.
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4%	125 mL/m²/hour	intravenous		Instructions: To each 1000 mL bag admix 50 mmol sodium bicarbonate. Or an alternative alkalinized intravenous infusion may be used as per institutional practice. Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice). Administration may continue past Day 5 if metHOTREXATe level is still elevated.
sodium bicarbonate	50 mmol	intravenous		Instructions: Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%. Dose of sodium bicarbonate is approximately 6 mmol/m²/hour when admixed bag is infused at 125 mL/m²/hour. Administration may continue past Day 5 if metHOTREXATe level is still elevated.
acetazolamide *	250 mg Four times daily	oral administration		Instructions: When required. Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice). Administration may continue past Day 5 if metHOTREXATe level is still elevated.
foliNIc acid (as calcium folinate)	30 mg flat dosing Every six hours	intravenous	2 minutes	Instructions: Administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice). If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information. Administration may continue past Day 5 if metHOTREXATe level is still elevated.

Day: 6

Medication	Dose	Route	Max duration	Details
procarbazine	100 mg/m² Once daily	oral administration		Instructions: Take at night with food. Do not drink alcohol and avoid large amounts of tyramine-rich foods (e.g. aged cheeses, cured meats, fermented foods and yeast extracts such as Marmite®) while being treated with this medicine. Talk to your doctor or pharmacist before taking medicines purchased over the counter from a pharmacy, supermarket or health food store. Round dose to closest multiple of 50 mg capsules.
filgrastim	5 microgram/kg Once daily	subcutaneous injection		Instructions: Give ONCE daily from Day 6 until neutrophil recovery. Round dose to nearest prefilled syringe dose of 300 micrograms or 480 micrograms.

Day: 7

Medication	Dose	Route	Max duration	Details
procarbazine	100 mg/m² Once daily	oral administration		Instructions: Take at night with food. Do not drink alcohol and avoid large amounts of tyramine-rich foods (e.g. aged cheeses, cured meats, fermented foods and yeast extracts such as Marmite®) while being treated with this medicine. Talk to your doctor or pharmacist before taking medicines purchased over the counter from a pharmacy, supermarket or health food store. Round dose to closest multiple of 50 mg capsules.

Cycle 6 - 14 days - R-MV: If in partial remission after 5 cycles

Day: 1

Medication	Dose	Route	Max duration	Details
paracetamol *	1000 mg flat dosing	oral administration		Instructions: 30 to 60 minutes prior to RITUximab.
loratadine *	10 mg	oral administration		Instructions: 30 to 60 minutes prior to RITUximab.
RITUximab *	375 mg/m²	intravenous	6 hours	Instructions: Consider administering corticosteroid premedication if previous doses not well tolerated or if clinically indicated, as per institutional practice. Start infusion at 100 mg/hour. If tolerated, rate can be increased by 100 mg/hour every 30 minutes to a maximum rate of 400 mg/hour, or as per institutional practice.

Day: 2

Medication	Dose	Route	Max duration	Details
vinCRISTine	1.4 mg/m² Cap dose per administration at: 2.8 mg	intravenous	10 minutes	Instructions: Diluted in a minibag. FOR INTRAVENOUS USE ONLY – fatal if given by any other routes. Warning vesicant—ensure vein is patent prior to administration, administer vesicant as per institutional policy and monitor for signs of extravasation throughout administration.
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4%	125 mL/m²/hour	intravenous		Instructions: To each 1000 mL bag admix 50 mmol sodium bicarbonate. Or an alternative alkalinized intravenous infusion may be used as per institutional practice. Commence at least 6 hours prior to metHOTREXATe infusion and run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate	50 mmol	intravenous		Instructions: Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%. Dose of sodium bicarbonate is approximately 6 mmol/m²/hour when admixed bag is infused at 125 mL/m²/hour.
acetazolamide *	250 mg Four times daily	oral administration		Instructions: When required. Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1µmol/L (level as per institutional practice).
metHOTREXATe *	3500 mg/m²	intravenous	120 minutes

Day: 3

Medication	Dose	Route	Max duration	Details
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4%	125 mL/m²/hour	intravenous		Instructions: To each 1000 mL bag admix 50 mmol sodium bicarbonate. Or an alternative alkalinized intravenous infusion may be used as per institutional practice. Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate	50 mmol	intravenous		Instructions: Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%. Dose of sodium bicarbonate is approximately 6 mmol/m²/hour when admixed bag is infused at 125 mL/m²/hour.
acetazolamide *	250 mg Four times daily	oral administration		Instructions: When required. Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1µmol/L (level as per institutional practice).
foliNIc acid (as calcium folinate)	30 mg flat dosing Every six hours	intravenous	2 minutes	Instructions: Starting 24 hours after start of metHOTREXATe infusion and continue to administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice). If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information.

Day: 4

Medication	Dose	Route	Max duration	Details
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4%	125 mL/m²/hour	intravenous		Instructions: To each 1000 mL bag admix 50 mmol sodium bicarbonate. Or an alternative alkalinized intravenous infusion may be used as per institutional practice. Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate	50 mmol	intravenous		Instructions: Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%. Dose of sodium bicarbonate is approximately 6 mmol/m²/hour when admixed bag is infused at 125 mL/m²/hour.
acetazolamide *	250 mg Four times daily	oral administration		Instructions: When required. Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1µmol/L (level as per institutional practice).
foliNIc acid (as calcium folinate)	30 mg flat dosing Every six hours	intravenous	2 minutes	Instructions: Administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice). If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information.

Day: 5

Medication	Dose	Route	Max duration	Details
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4%	125 mL/m²/hour	intravenous		Instructions: To each 1000 mL bag admix 50 mmol sodium bicarbonate. Or an alternative alkalinized intravenous infusion may be used as per institutional practice. Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice). Administration may continue past Day 5 if metHOTREXATe level is still elevated.
sodium bicarbonate	50 mmol	intravenous		Instructions: Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%. Dose of sodium bicarbonate is approximately 6 mmol/m²/hour when admixed bag is infused at 125 mL/m²/hour. Administration may continue past Day 5 if metHOTREXATe level is still elevated.
acetazolamide *	250 mg Four times daily	oral administration		Instructions: When required. Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice). Administration may continue past Day 5 if metHOTREXATe level is still elevated.
foliNIc acid (as calcium folinate)	30 mg flat dosing Every six hours	intravenous	2 minutes	Instructions: Administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice). If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information. Administration may continue past Day 5 if metHOTREXATe level is still elevated.

Day: 6

Medication	Dose	Route	Max duration	Details
filgrastim	5 microgram/kg Once daily	subcutaneous injection		Instructions: Give ONCE daily from Day 6 until neutrophil recovery. Round dose to nearest prefilled syringe dose of 300 micrograms or 480 micrograms.

Cycle 7 - 14 days - R-MVP: If in partial remission after 5 cycles

Day: 1

Medication	Dose	Route	Max duration	Details
paracetamol *	1000 mg flat dosing	oral administration		Instructions: 30 to 60 minutes prior to RITUximab.
loratadine *	10 mg	oral administration		Instructions: 30 to 60 minutes prior to RITUximab.
RITUximab *	375 mg/m²	intravenous	6 hours	Instructions: Consider administering corticosteroid premedication if previous doses not well tolerated or if clinically indicated, as per institutional practice. Start infusion at 100 mg/hour. If tolerated, rate can be increased by 100 mg/hour every 30 minutes to a maximum rate of 400 mg/hour, or as per institutional practice.
procarbazine	100 mg/m² Once daily	oral administration		Instructions: Take at night with food. Do not drink alcohol and avoid large amounts of tyramine-rich foods (e.g. aged cheeses, cured meats, fermented foods and yeast extracts such as Marmite®) while being treated with this medicine. Talk to your doctor or pharmacist before taking medicines purchased over the counter from a pharmacy, supermarket or health food store. Round dose to closest multiple of 50 mg capsules.

Day: 2

Medication	Dose	Route	Max duration	Details
procarbazine	100 mg/m² Once daily	oral administration		Instructions: Take at night with food. Do not drink alcohol and avoid large amounts of tyramine-rich foods (e.g. aged cheeses, cured meats, fermented foods and yeast extracts such as Marmite®) while being treated with this medicine. Talk to your doctor or pharmacist before taking medicines purchased over the counter from a pharmacy, supermarket or health food store. Round dose to closest multiple of 50 mg capsules.
vinCRISTine	1.4 mg/m² Cap dose per administration at: 2.8 mg	intravenous	10 minutes	Instructions: Diluted in a minibag. FOR INTRAVENOUS USE ONLY – fatal if given by any other routes. Warning vesicant—ensure vein is patent prior to administration, administer vesicant as per institutional policy and monitor for signs of extravasation throughout administration.
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4%	125 mL/m²/hour	intravenous		Instructions: To each 1000 mL bag admix 50 mmol sodium bicarbonate. Or an alternative alkalinized intravenous infusion may be used as per institutional practice. Commence at least 6 hours prior to metHOTREXATe infusion and run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate	50 mmol	intravenous		Instructions: Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%. Dose of sodium bicarbonate is approximately 6 mmol/m²/hour when admixed bag is infused at 125 mL/m²/hour.
acetazolamide *	250 mg Four times daily	oral administration		Instructions: When required. Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1µmol/L (level as per institutional practice).
metHOTREXATe *	3500 mg/m²	intravenous	120 minutes

Day: 3

Medication	Dose	Route	Max duration	Details
procarbazine	100 mg/m² Once daily	oral administration		Instructions: Take at night with food. Do not drink alcohol and avoid large amounts of tyramine-rich foods (e.g. aged cheeses, cured meats, fermented foods and yeast extracts such as Marmite®) while being treated with this medicine. Talk to your doctor or pharmacist before taking medicines purchased over the counter from a pharmacy, supermarket or health food store. Round dose to closest multiple of 50 mg capsules.
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4%	125 mL/m²/hour	intravenous		Instructions: To each 1000 mL bag admix 50 mmol sodium bicarbonate. Or an alternative alkalinized intravenous infusion may be used as per institutional practice. Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate	50 mmol	intravenous		Instructions: Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%. Dose of sodium bicarbonate is approximately 6 mmol/m²/hour when admixed bag is infused at 125 mL/m²/hour.
acetazolamide *	250 mg Four times daily	oral administration		Instructions: When required. Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1µmol/L (level as per institutional practice).
foliNIc acid (as calcium folinate)	30 mg flat dosing Every six hours	intravenous	2 minutes	Instructions: Starting 24 hours after start of metHOTREXATe infusion and continue to administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice). If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information.

Day: 4

Medication	Dose	Route	Max duration	Details
procarbazine	100 mg/m² Once daily	oral administration		Instructions: Take at night with food. Do not drink alcohol and avoid large amounts of tyramine-rich foods (e.g. aged cheeses, cured meats, fermented foods and yeast extracts such as Marmite®) while being treated with this medicine. Talk to your doctor or pharmacist before taking medicines purchased over the counter from a pharmacy, supermarket or health food store. Round dose to closest multiple of 50 mg capsules.
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4%	125 mL/m²/hour	intravenous		Instructions: To each 1000 mL bag admix 50 mmol sodium bicarbonate. Or an alternative alkalinized intravenous infusion may be used as per institutional practice. Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate	50 mmol	intravenous		Instructions: Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%. Dose of sodium bicarbonate is approximately 6 mmol/m²/hour when admixed bag is infused at 125 mL/m²/hour.
acetazolamide *	250 mg Four times daily	oral administration		Instructions: When required. Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1µmol/L (level as per institutional practice).
foliNIc acid (as calcium folinate)	30 mg flat dosing Every six hours	intravenous	2 minutes	Instructions: Administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice). If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information.

Day: 5

Medication	Dose	Route	Max duration	Details
procarbazine	100 mg/m² Once daily	oral administration		Instructions: Take at night with food. Do not drink alcohol and avoid large amounts of tyramine-rich foods (e.g. aged cheeses, cured meats, fermented foods and yeast extracts such as Marmite®) while being treated with this medicine. Talk to your doctor or pharmacist before taking medicines purchased over the counter from a pharmacy, supermarket or health food store. Round dose to closest multiple of 50 mg capsules.
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4%	125 mL/m²/hour	intravenous		Instructions: To each 1000 mL bag admix 50 mmol sodium bicarbonate. Or an alternative alkalinized intravenous infusion may be used as per institutional practice. Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice). Administration may continue past Day 5 if metHOTREXATe level is still elevated.
sodium bicarbonate	50 mmol	intravenous		Instructions: Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%. Dose of sodium bicarbonate is approximately 6 mmol/m²/hour when admixed bag is infused at 125 mL/m²/hour. Administration may continue past Day 5 if metHOTREXATe level is still elevated.
acetazolamide *	250 mg Four times daily	oral administration		Instructions: When required. Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice). Administration may continue past Day 5 if metHOTREXATe level is still elevated.
foliNIc acid (as calcium folinate)	30 mg flat dosing Every six hours	intravenous	2 minutes	Instructions: Administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice). If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information. Administration may continue past Day 5 if metHOTREXATe level is still elevated.

Day: 6

Medication	Dose	Route	Max duration	Details
procarbazine	100 mg/m² Once daily	oral administration		Instructions: Take at night with food. Do not drink alcohol and avoid large amounts of tyramine-rich foods (e.g. aged cheeses, cured meats, fermented foods and yeast extracts such as Marmite®) while being treated with this medicine. Talk to your doctor or pharmacist before taking medicines purchased over the counter from a pharmacy, supermarket or health food store. Round dose to closest multiple of 50 mg capsules.
filgrastim	5 microgram/kg Once daily	subcutaneous injection		Instructions: Give ONCE daily from Day 6 until neutrophil recovery. Round dose to nearest prefilled syringe dose of 300 micrograms or 480 micrograms.

Day: 7

Medication	Dose	Route	Max duration	Details
procarbazine	100 mg/m² Once daily	oral administration		Instructions: Take at night with food. Do not drink alcohol and avoid large amounts of tyramine-rich foods (e.g. aged cheeses, cured meats, fermented foods and yeast extracts such as Marmite®) while being treated with this medicine. Talk to your doctor or pharmacist before taking medicines purchased over the counter from a pharmacy, supermarket or health food store. Round dose to closest multiple of 50 mg capsules.

Supportive Care Factors

Factor	Value
Antiviral prophylaxis for hepatitis B virus:	Required for anti–HBc positive patients at risk of reactivation
Antiviral prophylaxis for herpes virus:	Routine antiviral prophylaxis recommended
Constipation risk:	laxatives are usually prescribed
Emetogenicity:	Variable
Folinic acid rescue for high dose methotrexate:	Mandatory
Growth factor support:	Recommended for primary prophylaxis
Hydration:	Routine hydration recommended
Hypersensitivity / Infusion related reaction risk:	High - routine premedication recommended
Pneumocystis jirovecii pneumonia (PJP) prophylaxis:	Routine antibiotic prophylaxis recommended
Tumour lysis syndrome prophylaxis:	Variable

Emetogenicity:

R-MPV:
MEDIUM to HIGH day 1, and days 3 to 7;
MEDIUM day 2, high dose metHOTREXATe may be highly emetogenic in certain patients.
R-MV:
MINIMAL day 1;
MEDIUM day 2, high dose metHOTREXATe may be highly emetogenic in certain patients.

PJP prophylaxis: If trimethoprim + sulfamethoxazole is used as prophylaxis, it is recommended to withhold at least 48 hours prior to high dose metHOTREXATe administration and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1µmol/L (as per institutional practice).

Tumour lysis syndrome prophylaxis: Recommended for cycle 1 and consider for subsequent cycles.

References

Tabernero J, Vyas M, Giuliani R, Arnold D, Cardoso F, Casali PG, Cervantes A, Eggermont AMM, Eniu A, Jassem J, Pentheroudakis G, Peters S, Rauh S, Zielinski CC, Stahel RA, Voest E, Douillard JY, McGregor K, Ciardiello F. Biosimilars: a position paper of the European Society for Medical Oncology, with particular reference to oncology prescribers. ESMO Open. 2017 Jan 16;1(6):e000142. doi: 10.1136/esmoopen-2016-000142. , PMID: 28848668

Lyman GH, Balaban E, Diaz M, Ferris A, Tsao A, Voest E, Zon R, Francisco M, Green S, Sherwood S, Harvey RD, Schilsky RL. American Society of Clinical Oncology Statement: Biosimilars in Oncology. J Clin Oncol. 2018 Apr 20;36(12):1260-1265. doi: 10.1200/JCO.2017.77.4893. Epub 2018 Feb 14., PMID: 29443651

Regimen details sometimes vary slightly from the published literature after recommendation by expert committee consensus.

* The medicines, doses, combinations, and schedule in this treatment regimen have been carefully reviewed against international best practice guidelines by specialists in medical oncology around New Zealand and this advice has been accepted for publication by Te Aho o Te Kahu (the Cancer Control Agency). Sometimes medicines that are used in routine clinical practice have not been through a formal review process by the NZ Medicines Regulator Medsafe and are therefore considered unapproved or off-label. These medicines are legally able to be prescribed through sections 25 and 29 of the Medicines Act and by obtaining informed consent from patients. All treatment regimens listed on this website have been through robust peer review and are considered an accepted standard of care, whether prescribed through sections 25 or 29 or carrying formal Medsafe Approval.

s29: This symbol indicates that some formulations of the associated medicine are legally only able to be prescribed under section 29 of the Medicines Act. You can see which formulations are section 29 by hovering over the s29 symbol. You can access full medication details from the New Zealand Formulary by clicking on the medication name. Each clinician retains full responsibility for ensuring they have complied with all relevant obligations and requirements of section 29 including obtaining informed patient consent prior to prescribing the applicable medicine.

Cancer Type —

Systemic Anti-Cancer Therapy Regimen Library

R-MPV alternating with R-MV Induction (LYM NHL B-cell PCNSL - R-MPV [RITUximab, metHOTREXATe, procarbazine and vinCRISTine] followed by high dose cytarabine)

Treatment Overview

Cycle 1 - 14 days - R-MPV [RITUximab (first dose), metHOTREXATe, procarbazine and vinCRISTine]

Cycle 2 - 14 days - R-MV [RITUximab, metHOTREXATe and vinCRISTine]

Cycle 3 - 14 days - R-MPV [RITUximab, metHOTREXATe, procarbazine and vinCRISTine]

Cycle 4 - 14 days - R-MV [RITUximab, metHOTREXATe and vinCRISTine]

Cycle 5 - 14 days - R-MPV [RITUximab, metHOTREXATe, procarbazine and vinCRISTine]

Cycle 6 - 14 days - R-MV: If in partial remission after 5 cycles

Cycle 7 - 14 days - R-MVP: If in partial remission after 5 cycles

Cycle details

Cycle 1 - 14 days - R-MPV [RITUximab (first dose), metHOTREXATe, procarbazine and vinCRISTine]

Cycle 2 - 14 days - R-MV [RITUximab, metHOTREXATe and vinCRISTine]

Cycle 3 - 14 days - R-MPV [RITUximab, metHOTREXATe, procarbazine and vinCRISTine]

Cycle 4 - 14 days - R-MV [RITUximab, metHOTREXATe and vinCRISTine]

Cycle 5 - 14 days - R-MPV [RITUximab, metHOTREXATe, procarbazine and vinCRISTine]

Cycle 6 - 14 days - R-MV: If in partial remission after 5 cycles

Cycle 7 - 14 days - R-MVP: If in partial remission after 5 cycles

Full details

Cycle 1 - 14 days - R-MPV [RITUximab (first dose), metHOTREXATe, procarbazine and vinCRISTine]

Day: 1

Day: 2

Day: 3

Day: 4

Day: 5

Day: 6

Day: 7

Cycle 2 - 14 days - R-MV [RITUximab, metHOTREXATe and vinCRISTine]

Day: 1

Day: 2

Day: 3

Day: 4

Day: 5

Day: 6

Cycle 3 - 14 days - R-MPV [RITUximab, metHOTREXATe, procarbazine and vinCRISTine]

Day: 1

Day: 2

Day: 3

Day: 4

Day: 5

Day: 6

Day: 7

Cycle 4 - 14 days - R-MV [RITUximab, metHOTREXATe and vinCRISTine]

Day: 1

Day: 2

Day: 3

Day: 4

Day: 5

Day: 6

Cycle 5 - 14 days - R-MPV [RITUximab, metHOTREXATe, procarbazine and vinCRISTine]

Day: 1

Day: 2

Day: 3

Day: 4

Day: 5

Day: 6

Day: 7

Cycle 6 - 14 days - R-MV: If in partial remission after 5 cycles

Day: 1

Day: 2

Day: 3

Day: 4

Day: 5

Day: 6

Cycle 7 - 14 days - R-MVP: If in partial remission after 5 cycles

Day: 1

Day: 2

Day: 3

Day: 4

Day: 5

Day: 6

Day: 7

Supportive Care Factors

References

Cancer Type
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