ADULT ACUTE LYMPHOCYTIC-LEUKEMIA - CRITICAL-REVIEW OF CURRENT KNOWLEDGE

PURPOSE: To analyze recent study results on adult acute lymphocytic leukemia (ALL) and discuss (1) controversies related to the optimal treatment for remission induction, maintenance, consolidation-intensification, and central nervous system (CNS) prophylaxis and (2) the role of allogeneic and autologous bone marrow transplantation (BMT). DESIGN: Review of the English-language literature concerning studies on adult ALL and comparisons with the pediatric ALL results when appropriate. RESULTS: Induction chemotherapy with a triple-drug regimen, including vincristine, anthracyclines; and steroids, yields the most favorable therapeutic-to-toxic ratio results. The addition of cyclophosphamide, asparaginase, or cytosine arabinoside (ara-C) to remission induction has not improved outcome. Consolidation-intensification therapy is beneficial in pediatric ALL and has been associated with increased cure rates in adult ALL, although the value of the individual components of therapy is difficult to assess. Based on the pediatric experience, future investigations in adult ALL should utilize higher dose-schedules of 6-mercaptopurine (6-MP), methotrexate, and asparaginase for consolidation-intensification therapy, The role of high-dose ara-C consolidation is not proven. Maintenance therapy with 6-MP and methotrexate is suggested based on the worse results in patients not receiving such maintenance. Allogeneic BMT is indicated in first remission in patients with high-risk for relapse (eg, Philadelphia-chromosome-positive [Ph-positive] ALL), while autologous BMT in first remission remains investigational. Mature B-cell ALL requires short-term/dose-intensive therapy with alternating hyperfractionated doses of cyclophosphamide and high doses of ara-C and methotrexate. T-cell ALL may benefit from ara-C plus cyclophosphamide consolidations. Based on certain risk features (ie, older age, high presenting white blood cell count, non-T-cell immunophenotype, Ph-positive karyotype, longer time to achieve remission), a high-risk group for systemic relapse (60% to 70% of patients) is identified with an expected cure rate of 20% to 25%; low-risk patients have an expected cure rate of 60% to 70%. Intrathecal chemotherapy may be sufficient as CNS prophylaxis, and its duration based on the expected risk of CNS relapse. CONCLUSION: Improvement in adult ALL prognosis has been modest. Future strategies may investigate increasing the dose-intensity of induction and consolidation-intensification therapy, incorporating new anti-ALL agents into the regimens, improving autologous BMT results (eg, purging, conditioning regimens), and appropriately using risk-oriented investigational strategies.