B. Meister et al., METHOTREXATE OSTEOPATHY IN INFANTS WITH TUMORS OF THE CENTRAL-NERVOUS-SYSTEM, Medical and pediatric oncology, 23(6), 1994, pp. 493-496
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.