Two Cases of Cerebral Involvement in Malignant Lymphoma (CD20+) That Responded to Combination Therapy with Rituximab and Cladribine

Cerebral involvement frequently occurs in association with progression or relapse of malignant lymphoma. Chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone, the standard chemotherapy for malignant lymphoma, is an ineffective treatment for cerebral involvement because these drugs cannot cross the blood-brain barrier. Therefore, various alternative strategies have been attempted. Although high-dose methotrexate combined with whole-brain radiotherapy is widely used to treat primary central nervous system lymphoma, there is no standard therapy to treat cerebral involvement in malignant lymphoma. Furthermore, high-dose methotrexate in combination with whole-brain radiotherapy is not always effective, and high rates of neurotoxicity are often observed, particularly in the elderly. To expand the therapeutic options for central nervous system involvement in recent years, systemic chemotherapies, including rituximab, high-dose methotrexate, and other agents that act during the S, G2, and M phases of the cell cycle, have been attempted. In our hospital, cladribine, a purine analogue with a cytocidal effect on resting malignant cells (G0/G1 phase of the cell cycle), has been used in combination with rituximab, which exhibits antitumor effects on nodal and extranodal lesions of relapsed and/or refractory B cell lymphomas, particularly cerebral lesions. Here, we report 2 representative cases of patients who were treated with cladribine plus rituximab and survived for 30 months (died of sepsis) and 52 months (still alive), respectively. The outcomes of these cases suggest that cladribine plus rituximab combination therapy with whole-brain radiotherapy may be very useful as salvage therapy for secondary central nervous system lymphoma and as initial therapy for primary central nervous system lymphoma.