Late isolated central nervous system relapse in childhood B-cell acute
lymphoblastic leukemia treated with intensified systemic therapy and
delayed reduced-dose cranial radiation: A report from the Children’s
Oncology Group study AALL02P2
Abstract
Background: Patients with late, occurring ≥18 months post-diagnosis,
isolated central nervous relapse (iCNS-R) of B-acute lymphoblastic
leukemia (ALL) have excellent outcomes with chemotherapy plus cranial
radiotherapy, with 5-yr overall survival (OS) approaching 80% in POG
9412. Subsequent relapse and radiation-related morbidity remain the
causes of treatment failure and long-term sequelae. COG AALL02P2 aimed
to maintain outcomes in patients with late iCNS-R using intensified
chemotherapy and a decrease in cranial irradiation from 1800 to 1200
cGy. Procedures: COG AALL02P2 enrolled 118 eligible patients with B-ALL
and early iCNS-R who received intensified systemic therapy, triple
intrathecal chemotherapy and 1200 cGy cranial irradiation delivered at
12 months, with maintenance chemotherapy continuing until104 weeks
post-diagnosis. Results: The 3-yr event-free and overall survival (EFS)
and OS were 64.3±4.5% and 79.6±3.8%, with 46.1% (18/39) of relapses
including the CNS. Of the 112 patients who completed therapy, 78
received protocol-specified radiation. Study enrollment was closed after
interim monitoring analysis showed inferior EFS compared to POG 9412.
Patients with initial NCI standard risk classification fared better than
high risk patients. Conclusions: COG AALL02P2 showed inferior EFS but
similar OS compared to POG 9412. Limitations included a small sample
size, more intensive prior therapies, and a significant number of
patients (34/118, 29%) who did not receive protocol-directed radiation
due to early relapse prior to 1 year or did not otherwise follow the
treatment plan. New approaches are needed to improve outcome for these
patients and determine the optimal timing and dose of cranial radiation
in the treatment of iCNS-R.