AbstractCyclic combination chemotherapy was administered to 26 patients with acute lymphoblastic leukemia who had relapsed in the bone marrow ≥ 6 months after elective cessation of therapy. Each patient had been in initial continuous complete remission for 36‐111 months (median, 47 months). Prednisone, vincristine, and doxorubicin induced second complete remissions in all patients within 1 month. Continuation therapy consisted of alternating 6‐week courses of 6‐mercaptopurine/methotrexate and vincristine/cyclo‐phosphamide with intervening reinforcement courses of prednisone/doxorubicin, for a total of 18 months. All patients received 4 weeks of late intensification therapy with the same agents used for remission reinduction. Periodic intrathecal methotrexate was given as reprophylaxis for subclinical central nervous system leukemia. The estimated rate of continuous failure‐free survival at 5 years is 31% ± 17% (2 SE). Eight patients remain free of leukemia for 42+ to 65+ months after completing therapy a second time. Adverse second events included 11 hematologic, 1 testicular, and 3 meningeal relapses. Patients who relapsed at more than 12 months after the completion of initial treatment have had significantly longer second remissions than patients whose first remissions were shorter (p = .04). None of the other six factors we analyzed showed predictive strength. These end results indicate that intensive cyclic continuation chemotherapy, as described here, will secure durable second remissions in approximately one‐third of the children with late bone m