Issues with high dose methotrexate therapy for primary central nervous system lymphoma
EANS Academy. Nakagawa H. 09/25/19; 275344; EP03101
Dr. Hidemitsu Nakagawa
Dr. Hidemitsu Nakagawa

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Background: The standard therapy for primary central nervous system lymphoma (PCNSL) is high dose methotrexate (HD-MTX) following irradiation therapy after confirmation of the histological diagnosis. However, we have frequently encountered cases in which chemotherapy cannot be performed before irradiation therapy, and the dead cases that showed chemotherapeutic resistance and severe adverse events despite chemotherapy being performed. Here, we present the pitfalls of the treatment method and HD-MTX therapy for PCNSL.
Patients and methods: Seventeen PCNSL patients were treated between January 2013 and May 2016; they all showed a pathological type of diffuse large B-cell lymphoma. Six of them received HD-MTX therapy as the initial treatment, with the following regimen of HD-MTX - a total of 3.5 - 6.0 g of MTX was administered over 3 to 4 hours and repeated every two weeks four to five times in total followed by leucovorin (LV) rescue.
Results: PCNSL frequently shows rapid growth following the pathological diagnosis, and therefore, irradiation therapy was initially selected for most patients as rapid and guaranteed treatment effects were expected. Three of the six patients died following HD-MTX therapy - one died of sepsis caused by high grade bone marrow suppression which was intensified by the high serum level of MTX sustained, while there was no clear cause of death in the other two patients, although the autopsy of one of them revealed gastrointestinal bleeding.
The median survival period for PCNSL has been extended by 1.5 times with HD-MTX therapy, although this therapy is high-risk treatment for older patients. The important factors of this therapy are the serum concentrations and the time course of serum MTX (the grade of decreasing of serum MTX).
The serum of MTX changes with every HD-MTX therapy, even in the same patients; therefore, the serum levels of MTX should be closely monitored.
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