Impact of three methods of treatment intensification on acute lymphoblastic leukemia in children: Long-term results of St Jude total therapy study X

Long-term follow-up observations are reported on 427 patients who received one of three different intensified therapies in total therapy study X for acute lymphoblastic leukemia (ALL). In the trial for 'standard-risk' ALL, 154 of 309 patients in complete remission were randomized to receive high-dose methotrexate (HDMTX, 1 g/m²) periodically during the first 72 of 120 weeks of standard continuation therapy with 6-mercaptopurine and oral MTX; the remaining 155 patients received 1800 cGy cranial irradiation and intrathecal MTX, followed by 6-mercaptopurine/MTX therapy interrupted from week 36-71 for substitution of two other pairs of drugs. At 9 years of follow-up, significantly higher proportions of patients in the HDMTX group have maintained complete remissions (64 ± 7%, SE, vs. 52 ± 6%, p = 0.03), hematologic remissions (73 ± 6% vs. 62 ± 6%, p = 0.03), and testicular remissions (94 ± 5% vs. 80 ± 8%, p = 0.03); however, the proportion continuing in central nervous system remission has been lower (84 ± 5% vs 93 ± 4%, p = 0.02). In the evaluation of teniposide cytarabine and delayed cranial irradiation for 'high-risk' ALL, 36 ± 9% of 101 patients are predicted to be event-free survivors at 9 years. Altogether, 217 (51%) of the 427 patients are event-free survivors after at least 7 years of follow-up (median, 9 years); an additional 75 patients are alive and free of leukemia for a median of 6.4 years after successful remission retrieval therapy, boosting the total number of long-term survivors to 292 (68%). These results establish the efficacy of HDMTX for patients with standard-risk ALL and indicate the potential of teniposide cytarabine for use in multiagent regimens for patients with high-risk disease. The overall survival figure, 68%, affords a benchmark for other studies assessing long-term outcome in ALL.