['lymphoma, large b-cell, diffuse']
['ngr-htnf', 'doxorubicin', 'cyclophosphamide', 'vincristine', 'prednisone']

        Inclusion criteria

          -  Histological or cytological diagnosis of (D)LBCL

          -  Disease exclusively localized into the CNS (brain, meninges, cranial nerves, eyes
             and/or spinal cord) both at first diagnosis and failure

          -  Progressive or recurrent disease

          -  Previous treatment with high-dose-methotrexate-based chemotherapy ± WBRT

          -  Presence of at least one target lesion, bidimensionally measurable

          -  Age 18 - 80 years

          -  ECOG performance status 0-3

          -  Adequate bone marrow (platelets >75.000/mm3, hemoglobin >8 g/dl, ANC >1.000/mm3),
             renal (serum creatinine <2 times UNL and creatinine clearance ≥40 mL/min), cardiac
             (VEF ≥50%), and hepatic (SGOT/SGPT <3 times UNL, bilirubin and alkaline phosphatase <2
             times UNL) function.

          -  Given written informed consent prior to any study specific procedures, with the
             understanding that the patient has the right to withdraw from the study at any time,
             without any prejudice. Informed consent signed by a patient's guardian is acceptable
             if the patient is not able to decide inclusion in the study due to cognitive
             impairment

        5.3 Exclusion criteria

          -  Known HIV disease or other chronic immunodeficiency

          -  Patients with positive flow cytometry examination of the CSF, but negative results in
             CSF conventional cytology, and without any other evidence of CNS disease

          -  Patients with concomitant extra-CNS disease at presentation or relapse

          -  Symptomatic coronary artery disease, cardiac arrhythmias not well controlled with
             medication or myocardial infarction within the last 6 months (New York Heart
             Association Class III or IV heart disease)

          -  Any other serious medical condition which could impair the ability of the patient to
             participate in the trial

          -  Concurrent treatment with other antineoplastic drugs

          -  Therapy with PPI (Proton Pump Inhibitors, that may interfere with chromogranine
             levels, see above). For gastroprotective therapy H2-blockers (i.e. ranitidine) are
             allowed.

          -  Pregnant and lactating female patients. Sexually active patients of child bearing
             potential must implement adequate contraceptive measures during study participation.

          -  Previous or concurrent malignancies at other sites diagnosed or relapsed within the
             last 3 years of follow-up. Patients with surgically cured in situ carcinomas and basal
             cell carcinoma of the skin are allowed.

          -  Presence of any psycological, familial, sociological or geographical condition
             potentially hampering compliance with the study protocol and follow-up schedule.
      