Treatment of Primary Central Nervous System Lymphoma with a Combination of Intraventricular Administration of Rituximab and Systemic Chemotherapy.

Primary CNS lymphoma (PCNSL) is an uncommon and progressive form of non-Hodgkin’s lymphoma. Since the majority of PCNSL cases are B-cell neoplasms expressing the CD20 surface antigen, treatment with Rituximab, the anti-CD20 antibody, might be a new therapeutic option. Since 2000, we have been performing a study on PCNSL patients with combined treatment of intraventricular immunochemotherapy and systemic chemotherapy. Ommaya reservoirs were placed in all these patients. The regimen of Intraventricular therapy is as follows: Methotrexate (MTX) 10mg plus Dexamethasone (Dex) 5mg followed by Cytosine arabinoside 25mg plus Dex 5mg via Ommaya reservoir in the first week, and Rituximab30mg plus Dex 2mg were given via Ommaya reservoir every other day for three times in the second week. Above treatments were finished 2 weeks a cycle until complete response (CR) was achieved and then the interval prolonged. Systemic chemotherapy includes regimen A and B. Regimen A: MTX 3~5g/m2 (D1), Vincristine 2mg (D1), Ifosfomide (IFO) 800mg/m2 (D2~4), and Dex. 10mg/m2 (D2~4). Serum MTX levels were monitored and Leucovin rescue began 24 hours after completion of MTX. Mesna rescue for IFO were also given conventionally; Regimen B: Carmustine 125 mg (D1), Teniposide 50mg (D1~3), Vindesine 4mg (D1), and Dex. 20mg (D1~4). Regimen A and B were given alternatively three weeks a cycle until CR was achieved, and then the interval prolonged. Brain MRI or PET was done every 2 or 3 months after treatment for evaluation of the response. Seven patients have been evaluated. The patients are 5 males and 2 females with the mean age of 51 years old (range: 32–82). One of the cases was a relapsed PCNSL who had achieved CR1 after whole-brain radiotherapy, systemic chemotherapy and autologous peripheral blood stem cell transplantation. He relapsed 33 months after CR1 and was enrolled in this study. After therapy he achieved CR2. But the second relapse occurred 18 months after CR2, and CR3 was achieved again after treatment with the same regimens, and total survival time has been 83 months. The other six cases were newly diagnosed PCNSL and all achieved CR after 2 to 3 months’ treatment. Among them only one patient experienced relapse after 26 months of remission, regimen A and intraventricular Rituximab were given but showed no remarkable response and died with survival time of 29 months. Other five patients are in continuing CR for 2, 12, 23, 25, and 40 months respectively. Two patients had nausea or vomiting after each intraventricular injection of Rituximab, but could relieve soon after. Ommaya reservoir infections occured in two patients, and cultures of the cerebrospinal fluid showed MRSCoN and MSSCoN, respectively. They were treated with vancomycin intravenously and via the reservoir. The infections were controlled quickly and their Ommaya reservoirs were kept. One 82 years old patient developed mild ulceration of the month and anus after treatment with regimen A. Hematological toxicities were mild, and could recover quickly with no need of transfusion or the use of G-CSF. In summary, the treatment of Intraventricular Rituximab via Ommaya reservoir combined with systemic chemotherapy for patients with PCNSL was safe and effective. This remedy is likely to improve the prognosis of such patients, but more cases need to be studied for the long-term result.