Effects of varying the interval between courses of methotrexate on its myelotoxic and anti-leukaemic activities

Open Access
Publisher Website
Google Scholar
Abstract
The toxicity produced by 2 courses of methotrexate separated by different intervals was studied in matched groups of rats. The maximum degree of neutropenia reached when courses were separated by 8 days or more was no greater than that seen after a single course of methotrexate. When courses were separated by < 8 days, significantly greater neutropenia resulted. The degree of neutropenia following the 2nd course of methotrexate was directly related to the level of depression of bone marrow cell numbers at the time of the 2nd course. The antileukemic effects of 2 courses of methotrexate, in terms of time of onset of leukemia and time of death in rats transplanted with a syngeneic T[thymus-derived]-cell leukemia, are similar when courses of methotrexate are separated by between 2 and 12 days. In this system, chemotherapeutic schedules using methotrexate may be designed on the basis of minimal host toxicity without prejudicing antileukemic effects. These results are discussed in relation to toxicity and antileukemic effects observed during UKALL [Working Party on Leukemia in Childhood] trials of treatment in acute lymphoblastic leukemia.