Effects of cranial radiation in children with high risk T cell acute lymphoblastic leukemia: a Pediatric Oncology Group report

Contemporary chemotherapy has significantly improved event-free survival am ong patients with T cell-lineage acute lymphoblastic leukemia (T-ALL). Unli ke B-precursor ALL, most investigators are still using cranial radiation (C RT) and are hesitant to rely solely on intrathecal therapy for T-ALL. In th is study we assessed the effects of CRT upon event-free survival and centra l nervous system (CNS) relapses in a cohort of children with high risk feat ures of T cell leukemia, In a series of six consecutive studies (1987-1995) patients were non-randomly assigned their CNS prophylaxis per individual p rotocol. These protocols were based on FOG 8704 which relied on rotating dr ug combinations (cytarabine/cyclophosphamide, teniposide/ Ara-C, and vincri stine/doxorubicin/6-MP/prednisone) postinduction, Modifications such as hig h-dose cytarabine, intermediate-dose methotrexate, and the addition of G-CS F, were designed to give higher CNS drug levels (decreasing the need for CR T), to eliminate epidophyllotoxin (decreasing the risk of secondary leukemi a), and to reduce therapy-related neutropenia (pilot studies FOG 9086, 9295 , 9296, 9297, 9398), All patients included in this analysis qualified for F OG high risk criteria, WBC >50 000/mm(3) and/or CNS leukemia, Patients with out CNS involvement received 16 doses of age-adjusted triple intra-thecal t herapy (TIT = hydrocortisone, MTX, and cytarabine) whereas patients with CN S disease received three more doses of TIT during induction and consolidati on. Patients who received CRT were treated with 2400 cGy (POG 8704) or 1800 cGy (POG 9086 and 9295), CNS therapy included CRT in 144 patients while th e remaining 78 patients received no radiation by original protocol design. There were 155 males and 57 females with a median age of 8.2 years, The med ian WBC for the CRT+ and CRT- patients were 186 000/mm(3) and 200 000/mm(3) , respectively. CNS involvement at diagnosis was seen in 16% of the CRT+ an d 23% of the CRT- groups. The complete continuous remission rate (CCR) was not significantly different for the irradiated vs non-irradiated groups (P = 0.46). The 3-year event-free survival was 65% (s.e. 6%) and 63% (s.e. 4%) for the non-irradiated vs the radiated group. However, the 3-year CNS rela pse rate was significantly higher amongst patients who did not receive CRT; 18% (s.e. 5%) vs 7% (s.e. 3%) in the irradiated group (P=0.012). Our analy sis in a non-randomized setting, suggests that CRT did not significantly co rrelate with event-free survival but omitting it had an adverse effect on t he CNS involvement at the time of relapse.