How is the central nervous system protected during ALL treatment?
One thing we've learned in the course of treating ALL over a number of decades is that if we don't give therapy that's directed at the central nervous system, meaning the brain and the fluid surrounding the spinal cord, there's unfortunately a high risk that the ALL is going to become active there at some point. Thankfully, we can very effectively prevent and treat that in patients using a number of different techniques.
Intrathecal chemotherapy is a component of treatment in all phases—induction, consolidation, and in many regimens as part of maintenance as well. This can be accomplished by having a lumbar puncture either at the bedside or with interventional radiology, where we take out a sample of the spinal fluid in order to assess for evidence of leukemia. And then while we are in there, we also administer some chemotherapy that is intended to help eradicate any low-level residual leukemia, low-level leukemia that may be in the spinal fluid, as well as to prevent any leukemic cells that might cross the blood-brain barrier from becoming active and setting up shop there, so to speak.
For patients that do have evidence of leukemia in their spinal fluid at diagnosis, we will follow very closely to make sure that that clears with the lumbar punctures that are part of therapy, and in some cases, depending on the extent of the amount of leukemia in there, we will actually give additional lumbar punctures in order to ensure that that clears promptly, sometimes even as often as twice a week initially, and then we back down from there.
Patients also may have something called an Ommaya reservoir placed, and an Ommaya reservoir is a small device that is placed under the scalp that permits us to have chemotherapy flow directly into the fluid surrounding the central nervous system. And this helps to avoid having lumbar punctures as regularly throughout treatment. And some centers make use of that as a way to have access essentially to the CNS space without having to do repeated lumbar punctures.
A number of other treatments that we use for patients who are at risk for or who develop central nervous system leukemia can in some cases include radiation therapy directed at the spine or brain, as well as systemic chemotherapy that penetrates the central nervous system and crosses the blood-brain barrier. As one example, methotrexate, given through the IV, as well as cytarabine given through the IV, can penetrate the blood-brain barrier and may be effective in the prevention or treatment of central nervous system leukemia in ALL and are actually parts of a number of treatment regimens.