Acute lymphoblastic leukemia in children. Advances and prospectus

During the past decade, advances in the treatment of childhood acute lymphoblastic leukemia (ALL) have continued, largely due to improved disease-free survival of poor-prognosis subgroups, improved sanctuary therapy, shortening of therapy duration, and salvage of relapsed patients with better chemotherapy regimens and with bone marrow transplantation. Nonetheless, more children continue to die of ALL than of any other childhood cancer. This review outlines central issues in the staging and treatment of ALL that should be addressed if the cure rate in childhood ALL is to be significantly improved. Present dilemmas in the staging of ALL include the following: lack of standardization of staging systems; complicated algorithms; variable application and interpretation of multivariate analyses; dynamic interactions between prognostic front end variables and subsequent treatment; ambiguity of prognostic factors that are predictive of outcome but biologically inexplicable; unsuccessful attempts to define a good-prognosis subgroup for the purpose of streamlining therapy to a minimum; and the interface between ALL and non-Hodgkin's lymphoma and myeloid leukemias. The remaining therapeutic problems include a lack of reliable in vitro tests of chemosensitivity and chemoresistance, inability to quantitate residual leukemia after remission induction or to detect drug-resistant clones of cells before they are clinically manifest, and delivery of optimum therapy and supportive care to all children with ALL.