Primary central nervous system lymphoma is rare. In involves lymphoma in the cerebral spinal fluid. You can also have central nervous system involvement with other types of lymphoma but that is not quite the same thing, though it may be treated the same.
A diagnosis is usually made via a lumbar puncture. The prognosis for PCNSL remains challenging and overall survival is lower than for other aggressive types of NHL.
The 2 year overall survival for each risk group is:
0-1 risk factors - 80%
2-3 risk factors - 48%
4-5 risk factors - 15%
The mainstay of treatment for PCNSL has been high dose Methotrexate, or Intrathecal Methotrexate. (Intrathecal means injected directly into the cerebral spinal fluid). Often that is accomplished using an Omaya reservoir, which is a port installed directly into the skull.
ARA-C (aka Cytarabine) is also a common treatment for PCNSL. Similar to Methotrexate it can be infused intrathecally. There is also a liposomal version of ARA-C called Depocyt. This form of ARA-C is encapsulated in a fat molecule. It will generally deliver more drug to the cancer and less to other normal tissues, thus reducing side effects. (Sometimes you will see it spelled Depocyte)
Combining both high dose methotrexate and ARA-C can result in even better outcomes, although more studies need to be done to confirm this. (2)
Another interesting treatment showing promise is intraventricular (directly into the space between the ventricles in the brain so it gets into the CSF) Rituxan for central nervous system involvement of NHL. (3) (4) Note that CNS involvement is not the same as "primary" central nervous system lymphoma. Therefore these results may not be applicable.
Whole brain radiation is controversial. While it often results in better disease control it comes with significant risk of cognitive problems. Over time studies have shown that while it may initially lead to superior progression free survival the cognitive impairment is too substantial. Skipping whole brain radiation and saving it for a relapse if that occurs spares the brain damage and does not adversely affect the overall survival. (5) (6) (7) (8)
There is no consensus about when is the most appropriate time to use a stem cell transplant for primary CNS lymphoma. Although upfront results using an SCT can yield some excellent results, the mortality rates are high. An upfront SCT can yield some excellent results without the neurotoxicity. Nevertheless the mortality rate is high especially in older patients. (9) Thiotepa based SCT's are yielding some very excellent results in elderly patients. (14) Relapsed patients often have fewer choices of effective treatments so an SCT for relapse is often a choice for consideration. (10)
Blood brain barrier disruption therapy is another promising avenue of treatment. Normally the blood brain barrier prevents many substances from passing through the blood vessels into the brain to protect the brain from harmful substances. The BBB procedure involves opening up that barrier by opening the blood vessels and then administering chemotherapy. (11) (12)
Maintenance therapies have not been widely explored for PCNSL. But some early work is being done. One study examined the use of maintenance lenalidomide and it showed a significant improvement in time to progression, without using radiation. (13) It is still just an early phase I study, but the results are encouraging.
The following article is a thorough review of the current knowledge of the biology, pathogenesis, and treatment of PCNSL. It includes summaries of many of the major studies on the subject making it easier to compare them.
The following paper is an excellent overview of how one expert in the field treats PCNSL.
This next article is also a lengthy review of the treatment of CNS lymphoma, both primary CNS and secondary CNS.
Randomized phase II trial on primary chemotherapy with high-dose methotrexate (HD-MTX) alone or associated with high-dose cytarabine (HD-araC) for patients with primary CNS lymphoma (I.E.L.S.G. #20 Trial): Tolerability, activity, and survival analyses
Intensive chemotherapy with thiotepa, busulfan and cyclophosphamide and hematopoietic stem cell rescue in relapsed or refractory primary central nervous system lymphoma and intraocular lymphoma: a retrospective study of 79 cases