Treatment scheme and the detailed treatment application for patients aged 15 to 55 years. CNS prophylaxis (**) started with a single intrathecal administration of methotrexate (MTX) on day 1 of prephase treatment, followed by triple intrathecal therapy with MTX, cytarabine, and dexamethasone in cycles A and B, twice per cycle. The second application in cycle A on days 12 and 33 was later omitted because triple intrathecal therapy may have aggravated cytopenia, particularly neutropenia, due to a systemic effect; furthermore, the patients increasingly complained about the number of intrathecal injections. Patients with documented CNS involvement received intrathecal chemotherapy twice weekly during induction until the cerebrospinal fluid cell count was normalized and the cytological examination was negative, and then followed the prophylactic scheme described above. Prophylactic application of granulocyte colony-stimulating factor after each cycle was part of the protocol. The aim was the application to therapy cycles at 21-day intervals. Before each cycle, hematologic regeneration with granulocytes >1000/mL, platelets >50 000/mL, the absence of grade 3/4 mucositis, or other severe organ toxicities was required. In Burkitt patients with stage I-II disease achieving a CR already after 2 cycles, chemotherapy could be stopped after 4 cycles if they had no initial extranodal involvement or a mediastinal tumor. The protocol for older patients (>55 years) consisted of cycles A and B alternatively repeated up to 6 total cycles (supplemental Figure 1). To reduce toxicity, HD-MTX was reduced to 500 mg/m2, cycle C with high-dose cytarabine was omitted, and intrathecal therapy with MTX was reduced to single to triple intrathecal therapy. c.i., continuous infusion; G-CSF, granulocyte colony-stimulating factor; h, hour; HD, high-dose; i.th., intrathecal; p.o., by mouth; s.c., subcutaneously; tu, tumor; VM26, teniposide.
