Re: Treatment of accidental intrathecal methotrexate overdose.

Widemann et al. (1) presented data on the use of cerebrospinal fl uid (CSF) exchange to remove methotrexate before carboxypeptidase G 2 (CPDG 2) administration among patients who had an accidental intrathecal methotrexate overdose. They reported that CSF drainage removed 32% – 58% of the methotrexate dose. Although they showed the percent decreases in CSF methotrexate concentration before and after CPDG 2 administration , they did not show the CSF methotrexate concentrations before CSF exchange. The absence of this information raises questions about the effectiveness of CSF drainage compared with CPDG 2 administration and about whether the combination of procedures removes more methotrexate than either proce dure alone. We are also curious about what method was used to determine the total amount of drug removed with CSF exchange. Calculating the amount extracted by using the difference in CSF methotrexate concentrations is complicated by ongoing movement of metho-trexate out of the CSF. The most accurate method would be to measure the total amount of methotrexate in the CSF collected from the exchange. In another recent report (2) that described the use of CSF exchange for accidental intrathecal methotrexate overdose , CSF exchange was performed over a 48-hour period. The graph of CSF methotrexate concentration versus time did not show a rapid drop in CSF metho-trexate concentration, suggesting that the exchange had minimal effect on CSF methotrexate elimination. It is unclear how the exchange was done in the Widemann et al. study because the method used was not described in detail. We conducted an informal survey among medical oncology and hematol-ogy units in New South Wales and the Australian Capital Territory (Australia) to fi nd out whether any had protocols to treat accidental intrathecal methotrexate overdose (Table 1). It proved diffi cult to reach a consultant on call at the different hospitals; nevertheless, the health care