HIGH-DOSE METHOTREXATE IN CHILDHOOD ALL

Abstract

An event-free survival is currently achieved in 70-80% of children diagnosed with acute lymphocytic leukemia (ALL). A decline in the long-term sequalae from therapy is a challenge at present. Due to the high incidence of central nervous system (CNS) relapse in ALL patients, cranial irradiation was introduced as a prophylactic measure in the beginning of the 1970s. Cranial irradiation, however, may cause secondary malignancies in the CNS. In recent years neurotoxicities have been demonstrated to follow cranial irradiation in a large proportion of ALL patients. Because of these deleterious effects, most ALL protocols are limited to the combination intrathecal and intravenous methotrexate as the standard for CNS prophylaxis. In the 1970s, an intermediate dose was administered, while from the 1980s a high dose of methotrexate was combined with intrathecal methotrexate. The regular methotrexate dose of later years has been in the range of 5-8 g/m2. The intravenous methotrexate dose has actually varied from 2 to 33.6 g/m2. The highest dose, 33.6 g/m2, has been without intrathecal instillation. In a study from Norway, high-dose methotrexate (6-8 g/m2