SURVIVAL OUTCOME FOLLOWING ISOLATED CENTRAL-NERVOUS-SYSTEM RELAPSE TREATED WITH ADDITIONAL CHEMOTHERAPY AND CRANIOSPINAL IRRADIATION IN CHILDHOOD ACUTE LYMPHOBLASTIC-LEUKEMIA

Purpose: An analysis of survival outcome following isolated central ne rvous system (CNS) relapse treated with craniospinal irradiation (CSI) and additional chemotherapy in children with acute lymphoblastic leuk emia (ALL) was conducted. Methods and Materials: Eighteen of 344 pedia tric patients with ALL who attained initial complete remission on the St. Jude Children's Research Hospital ''Study XI'' prospective protoco l (1984-1988) developed a CNS relapse as first adverse event. Median i nterval to isolated CNS relapse was 7.5 months (range = 2-40 months) a fter achieving initial complete remission. At diagnosis, 14 of the 18 children were categorized as ''high risk'' for subsequent leukemic rel apse. Preventive cranial irradiation [PCI (18 Gy)] was delivered as pl anned to one of the 14 ''high-risk'' children. The other 13 ''high-ris k'' patients experienced a CNS relapse during the first year of contin uation therapy prior to week 52 of planned PCI. All four ''low-risk'' patients experienced a CNS relapse beyond the first year of continuati on therapy; none were scheduled to receive PCI. Following isolated CNS relapse, all 18 patients were treated on a prospective contingency of ''Study XI'' trial consisting of intensified reinduction chemotherapy , weekly intrathecal methotrexate/hydrocortisone/Ara-C X 4-6 injection s, craniospinal irradiation (cranium to 24.0 Gy and spine to 15.0 Gy a t 1.5 Gy/fraction) and maintenance systemic therapy for a minimum of 1 year. Results: Ten of 18 patients remain in continuous complete secon dary remission at 17 to 50 months post-CNS relapse. Second sites of re lapse in the remaining eight children were as follows: CNS in four, bo ne marrow in three, and bilateral testicular in one patient. Each of t hese eight patients died of progressive leukemia. At a median followup of 40 months post-initial CNS relapse, the 3-year secondary Kaplan-Me ier survival and event-free survival are 72% and 56%, respectively. Mi nimal long-term neurotoxicity was associated with the treatment regime n. The most important prognostic factors predicting continuous seconda ry remission included white blood cell count at diagnosis (p = 0.05), and duration of initial remission (p = 0.04). Conclusion: This trial d emonstrates that more than one-half of patients may be successfully sa lvaged with intensified chemotherapy and craniospinal irradiation with out significant morbidity following an isolated CNS relapse, despite p revious multiagent chemotherapy though virtually no prior PCI in child hood ALL.