Background
Phase III RCT (COG AALL0232). 3,154 patients with newly diagnosed high-risk B-ALL (age 1–30). Evaluated dexamethasone vs prednisone during induction and maintenance in high-risk B-ALL. Also studied augmented BFM consolidation and use of cranial RT (18 Gy) reserved for CNS-3 disease only. Aimed to test whether dexamethasone reduces CNS relapse, thereby eliminating need for prophylactic cranial RT.
Interventions and follow up
Arm A: Prednisone induction + augmented BFM consolidation/maintenance + cranial RT 18 Gy (CNS-3 only)
Arm B: Dexamethasone induction + augmented BFM consolidation/maintenance + cranial RT 18 Gy (CNS-3 only)
Primary endpoint: EFS
mFollow up: 5.5 year
Arm B: Dexamethasone induction + augmented BFM consolidation/maintenance + cranial RT 18 Gy (CNS-3 only)
Primary endpoint: EFS
mFollow up: 5.5 year
Results
5-yr EFS (dexamethasone): 60.3% vs prednisone 59.7%, P=.59 — no significant difference
5-yr OS: 75.1% (dexamethasone) vs 75.3% (prednisone), P=.89
CNS relapse: Low in both arms (<3%) without prophylactic cranial RT
Osteonecrosis (dexamethasone): Significantly higher — 12.5% vs 6.5%, P<.001
5-yr OS: 75.1% (dexamethasone) vs 75.3% (prednisone), P=.89
CNS relapse: Low in both arms (<3%) without prophylactic cranial RT
Osteonecrosis (dexamethasone): Significantly higher — 12.5% vs 6.5%, P<.001
Adverse events
Main adverse events: Dexamethasone: significantly increased osteonecrosis, fractures, avascular necrosis (especially adolescents), mood/behavioral toxicity. Prednisone: greater myelosuppression. Cranial RT (CNS-3 only): neurocognitive effects in small subset.
Conclusions
Dexamethasone did not improve EFS over prednisone in high-risk B-ALL but significantly increased osteonecrosis, particularly in adolescents. The low CNS relapse rate without prophylactic cranial RT confirmed that modern intrathecal chemotherapy + augmented BFM makes routine prophylactic cranial RT unnecessary.
Key Limitations
Key Limitations: High-risk group is heterogeneous by current MRD criteria. Does not address MRD-directed therapy or targeted agents (imatinib for Ph+). Dexamethasone toxicity was significant and age-dependent. Long-term cognitive outcomes of patients treated without prophylactic cranial RT require follow-up.
Clinical Context
AALL0232 confirmed that prophylactic cranial RT can be safely eliminated from B-ALL treatment in the era of intensive intrathecal chemotherapy. Cranial RT is now reserved for CNS-3 disease only (18 Gy in most centers). This trial shaped the current standard of care where >95% of ALL patients receive no prophylactic cranial RT.
References