Optimizing MATRix, a combination of Methotrexate, Ara-C, Thiotepa and Rituximab given as an induction therapy, de-escalated in duration and total drug dose in comparison to the standard induction therapy and both treatments followed by a high dose therapy with autologous stem cell transplantation. The therapy is for patients with newly diagnosed primary lymphoma of the central nervous system.

Lab values

• Congenital or acquired immunodeficiency including HIV infection and previous organ transplantation. 2. Systemic lymphoma manifestation (outside the CNS). 3. Primary vitreoretinal lymphoma or primary leptomeningeal lymphoma without manifestation in the brain parenchyma or spinal cord 4. History of other malignancy that could affect compliance with the protocol or interpretation of results I. Participants with a history of curatively treated basal or squamous cell carcinoma of the skin, or in situ carcinoma of the cervix at any time prior to the study are eligible. II. Participants with low-grade, early-stage prostate cancer (Gleason score 6 or below, Stage 1 or 2) with no requirement for therapy at any time prior to study are eligible. III. Participants receiving adjuvant endocrine therapy for nonmetastatic, hormone receptor-positive breast cancer for 2 or more years prior to enrolment are eligible. IV. Participants with any other malignancy treated with curative intent and in remission without treatment for 2 years prior to enrolment are eligible. 5. Previous Non-Hodgkin lymphoma at any time. 6. Inadequate renal function (creatinine clearance < 60 ml/min (MDRD)). 7. Inadequate bone marrow, cardiac, pulmonary or hepatic function according to investigator´s decision 8. Active hepatitis B (defined as HBsAg positive OR HBsAg negative but Anti-HBc and HBV DNA positive) or C disease. 9. Concurrent treatment with other experimental drugs or participation in an interventional clinical trial with study medication being administered within the last 30 days before the start of this study. 10. Clinically relevant third space fluid accumulation according to the investigator's discretion. 11. Hypersensitivity to study treatment or any component of the formulation. 12. Taking any medications that are likely to cause interactions with the study medication 13. Known or persistent abuse of medication, drugs or alcohol. 14. Active bacterial, viral or fungal infection at the discretion of the investigator 15. Patients without legal capacity who are unable to understand the nature, significance and consequences of the trial and without designated legal representative. 16. Previous participation in this trial. 17. Persons who are in a relationship of dependency/employment with the sponsor and/or the investigator. 18. Any familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule 19. Current or planned pregnancy, nursing (breastfeeding) period 20. For fertile patients: Failure to use one of the following safe methods of contraception: intra-uterine device; hormonal contraception in combination with a mechanical method of contraception

• Immunocompetent patients with newly diagnosed primary diffuse large B-cell lymphoma of the central nervous system (PCNSL). 2. Male or female patients aged 18-65 years irrespective of KPS scale or 66-70 years with Karnofsky Performance Status Scale ≥ 50%. 3. Histologically or cytologically assessed diagnosis of high-grade Bcell lymphoma by local pathologist. Diagnostic sample obtained by stereotactic or surgical biopsy, CSF cytology examination or vitrectomy. 4. Disease exclusively located in the CNS. 5. At least one measurable lesion. 6. Previously untreated patients (previous surgery or ongoing steroid treatment permitted). 7. Negative pregnancy test (only women of childbearing potential) 8. Written informed consent obtained according to international guidelines and local laws by patient or authorized legal representative in case patient is legally not competent due to their PCNSL. 9. Ability to understand the nature of the trial and the trial related procedures and to comply with them (except the patients who are legally not competent due to their PCNSL; see inclusion criterion 8).