G-CSF, granulocyte colony-stimulating factor; IVCI, intravenous continuous infusion; IVP, intravenous push; IVPB, intravenous piggyback.

Patients with low-risk disease received 3 cycles of regimen A. Patients with high-risk disease received 4 alternating cycles of regimens A and B.

Rituximab was given once each cycle. Acute presentation of high-grade lymphoma and scheduling constraints may make it difficult to administer rituximab on the first day of each cycle. Rituximab was given up to 3 days before a chemotherapy cycle and any time within the cycle such that a total of 4 doses were given with this regimen for patients with high-risk disease. A missed dose was made up within 28 days of the last dose of IVAC.

Vincristine maximum 2-mg dose. Delays by a few days were allowed to accommodate scheduling or treatment of constipation.

Methotrexate levels were drawn 24, 48, and 72 hours after treatment, with anticipated decrement in levels of 10-fold every 24 hours.

Leucovorin was administered 24 hours after methotrexate and was initiated with a dose of 200 mg/m² intravenously (IV) followed by 25 mg/m² IV every 6 hours until the methotrexate level reached <50 nmol/L. Leucovorin was titrated for delayed methotrexate clearance or increases in creatinine.

Methotrexate (12 mg intrathecally [IT]) mixed with cytarabine (50 mg IT) given on day 1. Hydrocortisone 50 mg was given to reduce arachnoiditis.

G-CSF: Restarted after methotrexate levels had dropped below 50 nmol/L and continued until absolute neutrophil count (ANC) reached >1000 cells per μL.

If pegfilgrastim was not available, G-CSF was given once per day until ANC >1000 cells per μL was substituted.

Patients with high-risk disease received additional IT cytarabine 50 mg on day 3.