CNS-directed therapy in young children with T-lineage acute lymphoblastic leukemia: High-dose methotrexate versus cranial irradiation.

BACKGROUND

Prophylactic use of cranial radiation therapy (CRT) in young children with acute lymphoblastic leukemia (ALL) is associated with significant long-term morbidity. Therefore, current treatment protocols for pediatric B-precursor ALL have abandoned prophylactic CRT in favor of intrathecal chemotherapy, combined with either high-dose methotrexate infusions (HD-MTX) or intensive systemic chemotherapy. In contrast, prophylactic CRT continues to be used in children with T-lineage ALL (T-ALL), who historically have had an inferior prognosis. We conducted a retrospective cohort study to determine the effect on survival of substituting HD-MTX for CRT in young children with T-ALL, a group that faces a high risk of long-term sequelae from CRT.

PROCEDURE

Twenty-six children, diagnosed with T-ALL between the ages of 1 and 5 years, were treated on the same high-risk leukemia protocol. Central nervous system (CNS) directed therapy consisted of either CRT (1,800 cGy) or HD-MTX (three doses of 8 g/m2), depending on the treatment era in which patients were diagnosed.

RESULTS

Of the 24 patients who entered remission, 12 received CRT and 12 received HD-MTX. Five-year event-free survival (EFS) (+/-SE) was 92 +/- 8% in the HD-MTX group versus 75 +/- 13% in the CRT group (P=0.23). Five-year overall survival (OS) was 100% in the HD-MTX group versus 75 +/- 13% in the CRT group (P=0.07). There were no CNS recurrences in the HD-MTX group. One patient treated with CRT developed a brain tumor.

CONCLUSIONS

The use of HD-MTX instead of CRT as CNS-directed therapy in very young children with T-ALL does not compromise survival, while avoiding the adverse long-term effects of cranial irradiation.