METHOTREXATE OSTEOPATHY IN INFANTS WITH TUMORS OF THE CENTRAL-NERVOUS-SYSTEM

Methotrexate osteopathy, previously reported as a complication of main tenance-therapy for acute lymphoblastic leukemia, is characterized by osteopenia, particularly involving the lower extremities, thick, dense provisional zones of calcification, growth arrest lines, and corner f ractures resembling scurvy. In attempts to postpone radiotherapy in in fants under three years of age, the multicentric German therapy protoc ol for childhood central nervous system tumors (HIT-89 protocol) has e mployed high cumulative methotrexate doses. Here we describe osteopath y in three patients as a toxic side effect after administration of cum ulative methotrexate doses of 20 g/m2, 80 g/m2 and 135 g/m2. The high prevalence of this adverse effect in infants with tumors of the centra l nervous system may be attributed to the long-term therapy with high cumulative methotrexate-doses. Both factors may favor intracellular ac cumulation of methotrexate and formation of methotrexate-polyglutamate s and may be responsible for bone toxicity. Apparently the susceptibil ity of the rapidly growing skeletal structures of infants under three years of age to this toxic side effect of methotrexate is remarkably h igh. (C) 1994 Wiley-Liss, Inc.