R-CDOP Combined With Intrathecal Methotrexate for DLBCL Patients With High-risk of CNS Relapse

Inclusion Criteria: 1. Age range from 18 to 75 years; 2. ECOG performance status: 0-2; 3. Histopathologically confirmed untreated diffuse large B-cell lymphoma (cell origin can be distinguished according to Hans algorithm) , And fulfilled the following criteria for high-risk CNS recurrence: 1. CNS-IPI 4-6; 2. The lymphoma involved testis, breast (excluding unilateral breast and less than 5 cm mass), adrenal gland, kidney, paranasal sinus, paravertebral, and bone marrow and other sites; 3. PCLBCL-leg; 4. Subjects have at least one measurable lesion: the long axis of the lymph node shall be\>1.5 cm, the long axis of the extranodal lesions shall be\>1.0 cm; 5. Bone marrow hematopoiesis was essentially normal: WBC≥3.5 ×10\^9/L, ANC≥1.5×10\^9/L, PLT≥80×10\^9/L, Hb≥90 g/L. Abnormal peripheral blood indices, as a result of lymphoma invading the bone marrow or spleen, permitted enrollment at the discretion of the investigator; 6. Liver function: total bilirubin, ALT, AST \< 1.5×UNL (upper limit of normal); 7. Renal function: Cr \< 1.5×UNL and creatinine clearance≥30 ml/min; 8. Echocardiography or nuclide cardiac function testing with LVEF≥50%; 9. Patients in the reproductive period agreed to appropriate contraception. Women in the reproductive period had a negative serum pregnancy test within 2 weeks before enrollment; 10. Consent to provide pathological tissue specimens (wax blocks within half a year or 20 slides for paraffin tissue sections); 11. Life expectancy≥3 months; 12. Signed informed consent; Exclusion Criteria: 1. Patients with a known history of severe allergy to humanized or murine mAbs, or any contraindication to R-CDOP, intrathecal MTX; 2. Patients with evidence of CNS involvement (baseline cerebrospinal fluid, imaging, symptoms); 3. Special types of diffuse large B-cell lymphoma patients who are not suitable for induction therapy with R-CDOP, such as PMBCL, double-hit large B-cell lymphoma, etc; 4. Clinically significant cardiac conditions, including severe cardiac insufficiency: New York Heart Association (NYHA) cardiac insufficiency class IV, unstable angina, acute myocardial infarction within 6 months prior to screening, congestive heart failure, and Q-Tc interval greater than 500 ms; 5. Those who had a second degree or greater operation within three weeks before treatment; 6. Diagnosed with a malignancy other than lymphoma or under treatment, with the following exceptions: 1. Had received treatment with curative intent and had not developed malignancy with known active disease ≥ 5 years prior to enrollment; 2. Basal cell carcinoma of the skin (other than melanoma) that has been adequately treated with no evidence of disease; 3. Carcinoma in situ of the cervix that has been adequately treated with no evidence of disease; 7. Had significant coagulation abnormalities; 8. Any previous antilymphoma therapy other than short-term corticosteroids (up to 10 days); 9. Those with severe active infection; 10. Other serious, uncontrolled concomitant conditions that may affect protocol adherence or interfere with interpretation of results include uncontrolled diabetes mellitus, or pulmonary disease (interstitial pneumonia, obstructive pulmonary disease, and a history of symptomatic bronchospasm), hypertension, and others; 11. HBV (HBsAg positive and HBV-DNA ≥ 104 IU / ml), HCV (HCV antibody positive and HCV-RNA measurable); And subjects with other acquired, congenital immunodeficiency diseases, including but not limited to those with HIV infection; 12. Pregnant or lactating women;