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 cGy of hypofractionated craniospinal irradiation (CSI) in children with central nervous system (CNS) relapse following first remisssion of acute lymphoblastic leukemia (ALL).


METHODS
Nineteen patients with isolated CNS relapse and 4 with combined CNS/marrow or CNS/testicular relapse received treatment according to Children's Hospital of Philadelphia (CHOP) protocols CHP-449 and CHP-497. CNS treatment included intrathecal methotrexate, cytarabine, and hydrocortisone and 1,800 cGy CSI in 16 fractions over 12 months. Systemic therapy consisted of reinductions with vincristine, prednisone, and daunorubicin and reconsolidations with cytarabine, etoposide, and L-asparaginase every 56 days for 2 years. Outcome measures were event-free survival (EFS), survival, growth, and neuropsychologic assessment or school performance.


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% (CI95 = 38-78%) and 54% (CI95 = 32-76%). Events include 2 second CNS, 4 marrow, 1 testicular, and 2 testicular/marrow relapses and 1 secondary leukemia. EFS is 100% (CI95 = 93-100%) in 9 patients with recurrence more than 26 months from diagnosis. Three patients have significant treatment-related reduction in stature. Median full-scale IQs of 6 patients tested were 112 pretreatment and 111 posttreatment among surviving patients. All 17 survivors attend regular school, but 2 receive supplementary special services.


CONCLUSIONS
Lower dose, hypofractionated CSI, intrathecal chemotherapy, and moderately intensive systemic chemotherapy provide excellent disease control for patients with late isolated CNS or combined marrow and CNS relapse. Children with brief first remissions remain at substantial risk of subsequent relapse with this therapy, especially in the marrow and testes.
Belasco
J B
JB
Division of Oncology, The Children's Hospital of Philadelphia, and Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Goldwein
J W
JW
Simms
S
S
Griffin
G
G
D'Angio
G
G
Lange
B
B
D000293:Adolescent; D000328:Adult; D016543:Central Nervous System Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000628:therapy*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D015996:Survival Rate