INTENSIVE RETREATMENT PROTOCOL FOR CHILDREN WITH AN ISOLATED CNS RELAPSE OF ACUTE LYMPHOBLASTIC-LEUKEMIA

Purpose: To assess the salvage rate and long-term complications among children treated with an intensive regimen for isolated CNS relapse du ring first remission of acute lymphoblastic leukemia (ALL). Patients a nd Methods: Twelve boys and eight girls, diagnosed at a median age of 4 years, had CNS relapse at a: median age of 7 years. Five had CNS leu kemia at presentation, while five completed treatment before relapse. First complete remission lasted a median of 22.5 months. Ten patients had received cranial irradiation plus intrathecal (IT) therapy, and th e remainder had received high-dose intravenous and/or IT methotrexate (MTX) as CNS-directed treatment. Retrieval therapy consisted of a five -agent intensive reinduction regimen followed by continuation therapy with four rotating drug pairs. Triple-IT therapy was administered week ly for 4 to 5 weeks, then every 6 weeks until craniospinal radiation ( cranium, 24 Gy; spine, 15 Gy; both sites, 1.5 Gy per fraction) was adm inistered. Results: All 20 children achieved a second complete remissi on. The 5-year estimate of disease-free survival (mean +/- SE) was 70% +/- 11%. Thirteen patients remain in remission at 71 + to 126 + month s (median, 104 +), and 10 of 13 patients tested have normal IQ scores. Four patients have had a second relapse (one CNS and three non-CNS), and three have developed other malignancies. Prior cranial irradiation was associated with subsequent failure; only three of 10 patients who previously received radiotherapy, compared with all of the other 10 p atients, remained in second remission. Conclusion: This intensive retr ieval therapy is effective and well tolerated by children with an isol ated CNS relapse of ALL, especially those who have not received prior cranial irradiation. Most patients have no significant neuropsychologi c impairment.