Delayed Clearance of Methotrexate in a Patient with Malignant Lymphoma

Abstract

A female patient with multi-drug resistant malignant lymphoma who had bulky abdominal mass, in clinical stage IV A (DSC, B-cell type) was treated by high-dose methotrexate (MTX), (5g. followed by 7g.) with CF rescue. MTX serum concentration decreased under 1×10^-6 M at 72 hours, but remained toxic concentration over 1×10^-7 M for 68 days. The patient died ten days after the day when MTX could not detect in her serum. At autopsy, MTX was detected 4.4×10^-7 M in the liver and 4.0×10^-8 M in the tumor tissue. The patient maintained good urinary flow and creatinin clearance keeping always over 70ml/min. The cause of delayed clearance of MTX in this case was thought to be “re-entry” of MTX from the tumor. On High-dose MTX therapy, bulky mass was assumed to be a risk factor for delayed clearance of MTX due to “re-entry”. Severe myelotoxicity could be prevented by ordinary CF rescue therapy. But hepatocellular dysfuncotin without elevation of hepato-biliary enzyme in her serum might be related with MTX hepatotoxicity.