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Effects of cranial radiation in children with high risk T cell acute lymphoblastic leukemia: a Pediatric Oncology Group report. Leukemia 2000 Mar;14(3):369-73 PMID: 10720128

Pubmed ID

10720128

Abstract

Contemporary chemotherapy has significantly improved event-free survival among patients with T cell-lineage acute lymphoblastic leukemia (T-ALL). Unlike B-precursor ALL, most investigators are still using cranial radiation (CRT) and are hesitant to rely solely on intrathecal therapy for T-ALL. In this study we assessed the effects of CRT upon event-free survival and central nervous system (CNS) relapses in a cohort of children with high risk features of T cell leukemia. In a series of six consecutive studies (1987-1995) patients were non-randomly assigned their CNS prophylaxis per individual protocol. These protocols were based on POG 8704 which relied on rotating drug combinations (cytarabine/cyclophosphamide, teniposide/Ara-C, and vincristine/doxorubicin/6-MP/prednisone) postinduction. Modifications such as high-dose cytarabine, intermediate-dose methotrexate, and the addition of G-CSF, were designed to give higher CNS drug levels (decreasing the need for CRT), to eliminate epidophyllotoxin (decreasing the risk of secondary leukemia), and to reduce therapy-related neutropenia (pilot studies POG 9086, 9295, 9296, 9297, 9398). All patients included in this analysis qualified for POG high risk criteria, WBC >50000/mm3 and/or CNS leukemia. Patients without CNS involvement received 16 doses of age-adjusted triple intra-thecal therapy (TIT = hydrocortisone, MTX, and cytarabine) whereas patients with CNS disease received three more doses of TIT during induction and consolidation. 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 the 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 median WBC for the CRT+ and CRT- patients were 186000/mm3 and 200000/mm3, respectively. CNS involvement at diagnosis was seen in 16% of the CRT+ and 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 relapse 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 analysis in a non-randomized setting, suggests that CRT did not significantly correlate with event-free survival but omitting it had an adverse effect on the CNS involvement at the time of relapse.

Author List

Laver JH, Barredo JC, Amylon M, Schwenn M, Kurtzberg J, Camitta BM, Pullen J, Link MP, Borowitz M, Ravindranath Y, Murphy SB, Shuster J

Author

Bruce M. Camitta MD Clinical Professor in the Medicine department at Medical College of Wisconsin




Scopus

2-s2.0-0034009371   17 Citations

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Antineoplastic Combined Chemotherapy Protocols
Central Nervous System
Child
Child, Preschool
Cohort Studies
Combined Modality Therapy
Cranial Irradiation
Cyclophosphamide
Cytarabine
Disease-Free Survival
Female
Humans
Infant
Injections, Spinal
Leukemia-Lymphoma, Adult T-Cell
Leukemic Infiltration
Male
Methotrexate
Podophyllotoxin
Prognosis
Remission Induction
Risk
Teniposide
Treatment Outcome
jenkins-FCD Prod-353 9ccd8489072cb19f5b9f808bb23ed672c582f41e