Therapeutic management of refractory or relapsed primary central nervous system lymphomas.
Despite the high rate of complete remission achieved with first-line therapy, 10-15% of immunocompetent PCNSL patients are treatment refractory while 35-60% relapse and die of lymphoma within a few months. In many cases, salvage therapy produces a second complete remission with consequent symptomatic and survival improvement. Due to the heterogeneity of both first and second line therapies employed, the optimal schedule for salvage therapy can not be identified. Nevertheless, some therapeutic guidelines could be suggested. Radiotherapy is an effective option for both previously irradiated and radiotherapy naïve patients. Some authors have been able to minimize the incidence of actinic toxicity by using chemotherapy alone at failure. In patients that have relapsed after receiving high-dose methotrexate (HD-MTX), the same drug again has been successfully employed while HD-cytarabine has been the most widely used cytostatic. Ocular recurrence can be treated with cytarabine or focal radiotherapy. Meningeal relapse can be treated with spinal cord irradiation, intrathecal and/or systemic chemotherapy. Salvage therapy, beyond improving survival, constitutes the selection ground for testing active agents. The addition of other cytostatics to HD-MTX has been empirically based and without a clear survival benefit, but with a higher toxicity. Intriguing preliminary results from small pilot studies are now available with topotecan, rituximab, temozolomide, PCV regimen and HD-chemotherapy supported by autologous or allogeneic peripheral blood stem cells transplantation. Considering its positive effect on survival and the potential improvement in neurological symptoms and quality of life, salvage therapy seems to be a valuable treatment in PCNSL patients. Finally, the inclusion of relapsing or progressive PCNSL patients into second-line prospective clinical trials for testing therapeutic agents should be strongly encouraged.
Reni
M
M
Department of Radiochemotherapy, San Raffaele H. Scientific Institute, Milan, Italy. reni.michele@hsr.it
Ferreri
A J
AJ
D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D016543:Central Nervous System Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy / Q000628:therapy*; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007278:Injections, Spinal; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy / Q000628:therapy*; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy / Q000628:therapy*; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D012074:Remission Induction; D012189:Retrospective Studies; D016879:Salvage Therapy; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
D000964:Antimetabolites, Antineoplastic; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone; D008727:Methotrexate