Improved survival of children with isolated CNS relapse of acute lymphoblastic leukemia: A Pediatric Oncology Group study

Purpose: Isolated meningeal relapse in children with acute lymphoblastic le ukemia (ALL) usually has been followed by bone marrow relapse and limited s urvival. The purpose of this study was to prevent marrow relapse by adminis tering intensive therapy before delayed craniospinal radiation. Patients and Methods: Eighty-three patients with ALL in first bone marrow r emission with an isolated CNS relapse were treated with systemic chemothera py known to enter into the CSF and intrathecal chemotherapy for 6 months. C raniospinal irradiation (24 Gy cranial/15 Gy spinal) was then administered, followed by 1.5 years of maintenance chemotherapy. Results: All 83 patients achieved a second remission. The 4-year event-free survival (EFS) rate was 71.1% +/- 5.3%. There was a fourfold increased ris k of relapse for children whose initial remission was less than 18 months. The 4-year EFS rate for patients with a first complete remission greater th an or equal to 18 months was 83.3% +/- 5.3%, and for those with a first com plete remission less than 18 months, it was 46.2% +/- 10.2% (P =.0002.) The re was a low incidence of neurologic toxicity and an unexpectedly high rate of allergic reactions to L-asparaginase. Five patients developed secondary malignancies: two with acute nonlymphoblastic leukemia during therapy, one with myelodysplasia after therapy, and two with brain tumors 1.5 to 2 year s after cessation of therapy. Conclusion: For children with ALL and an isolated CNS relapse, treatment th at delays definitive craniospinal irradiation by 6 months to allow for more intensive systemic and intrathecal chemotherapy results in better EFS than has been previously reported. Using this approach, the long-term prognosis for children with first complete remission greater than or equal to 18 mon ths is comparable to that at the time of original diagnosis of ALL. J Clin Oncol 17:3745-3752. (C) 1999 by American Society of Clinical Oncology.