Patients with previously untreated diffuse large B-cell lymphoma will receive standard treatment with R-CHOP (rituximab,cyclosphosphamide, doxorubicin, vincristine, and prednison) for 6 cycles, cycle length is 14 or 21 days. In addition, valproate is given three times daily day 1-3 in escalated doses. The rationale for adding valproate to standard treatment is invitro data indicating a sensitizing effect to chemotherapy, and an increase in CD 20-expression.

Patients are included in 3+3 cohorts with escalation of valproate dose, planned dos levels are 30, 60, 80, 100, 120, 140 mg/kg/day. A total of 20 patients will be treated at the MTD.

Inclusion Criteria:

• Age 18-80 years
• Histologically confirmed (according to the WHO classification) diffuse large B-cell lymphoma stage II-IV
• No previous treatment for lymphoma. Corticosteroids for alleviation of lymphoma associated symptoms are allowed
• WHO performance status 0-2
• HIV negativity
• Seronegativity for HCV, HBsAg, anti-HBc, or other active infection uncontrolled by treatment
• Absence of psychiatric illness or condition which could interfere with the subjects ability understand the requirements of the study
• Absence of neurological or neuropsychiatric disorder, interfering with the requirements of the study
• Absence of hearing impairment > grade 2
• Absence of porphyria
• In females: absence of pregnancy and lactation
• All subjects must agree to abstain from donating blood while taking study drug therapy and for one week following discontinuation of study drug therapy
• All subjects must agree not to share study medication with another person, and to return all unused study drug to investigators
• Written informed concent according to ICH/GCP and Swedish regulations