Hypofractionated moderate dose radiation, intrathecal chemotherapy, and repetitive reinduction/reconsolidation systemic therapy for central nervous system relapse of acute lymphoblastic leukemia in children

Background. We assessed efficacy and morbidity of chemotherapy and 1,800 cG y of hypofractionated craniospinal irradiation (CSI) in children with centr al nervous system (CNS) relapse following first remisssion of acute lymphob lastic leukemia (ALL). Procedure. Nineteen patients with isolated CNS relap se and 4 with combined CNS/marrow or CNS/testicular relapse received treatm ent according to Children's Hospital of Philadelphia (CHOP) protocols CHP-4 49 and CHP-497. CNS treatment included intrathecal methotrexate, cytarabine , and hydrocortisone and 1,800 cGy CSI in 16 fractions over 12 months. Syst emic therapy consisted of reinductions with vincristine, prednisone, and da unorubicin and reconsolidations with cytarabine, etoposide, and L-asparagin ase every 56 days for 2 years. Outcome measures were event-free survival (E FS), survival, growth, and neuropsychologic assessment or school performanc e. Results. Follow-up of survivors from first relapse ranges from 52 to 133 months (median 91 months). Actuarial survival and EFSat 10 years are 58% ( Cl95 = 38-78%) and 54% (Cl95 = 32-76%). Events include 2 second CNS, 4 marr ow, 1 testicular, and 2 testicular/marrow relapses and 1 secondary leukemia . EFS is 100% (Cl95 = 93-100%) in 9 patients with recurrence more than 26 m onths from diagnosis. Three patients have significant treatment-related red uction in stature. Median fullscale IQs of 6 patients tested were 112 pretr eatment and 111 posttreatment among surviving patients. All 17 survivors at tend regular school, but 2 receive supplementary special services. Conclusi ons. Lower dose, hypofractionated CSI, intrathecal chemotherapy, and modera tely intensive systemic chemotherapy provide excellent disease control for patients with late isolated CNS or combined marrow and CNS relapse. Childre n with brief first remissions remain at substantial risk of subsequent rela pse with this therapy, especially in the marrow and testes. Med. Pediatr. O ncol. 34:125-131, 2000. (C) 2000 Wiley-Lies, inc.