Prevention of meningeal leukemia. Review of 20 years of research and current recommendations

Abstract

By use of prophylactic CNS therapy, the incidence of meningeal relapse has been dramatically reduced and the length of the initial bone marrow remission has been greatly prolonged in children with acute lymphoblastic leukemia. Pinkel performed a controlled study in which 94 patients were randomized to one of two regimens of presymptomatic CNS therapy, or received no prophylactic CNS therapy. This crucial study showed that prophylactic CNS therapy was very useful both in preventing meningeal relapse and in prolonging the duration of complete remission. Then, many additional regimens for prophylactic CNS therapy were tried on thousands of children worldwide in an effort to improve upon these results. Among the many CNS therapy regimens that were tried, none gave results better than the original St. Jude regimen. Our knowledge of CNS leukemia in general has greatly increased, but the last 20 years have brought us no further significant progress as to improved results in preventing meningeal leukemia. The many novel and innovative CNS therapy regimens that have been tried have yielded essentially the same results as to prevention of meningeal leukemia and as to duration of disease-free survival. Five to ten percent, or fewer in patients at low risk, still show meningeal relapse, and nearly one half of children with ALL still have hematologic relapse within the first 5 years following initiation of therapy. The goal now is to reduce neurotoxicity. Thus, progress has been stymied and we now await some new addition to therapy that will dramatically improve our results. Nonetheless, there are still many promising avenues of research yet to be explored. Meningeal leukemia remains a fascinating and satisfying field of clinical research.