Methotrexate myelopathy with extensive transverse necrosis: report of an autopsy case.

The patient was a 70-year-old woman with lymphoplasmacytic lymphoma which showed a predominantly diffuse involvement of the bone marrow and kidney. Because atypical lymphocytes appeared in the cerebrospinal fluid, the intrathecal administration of methotrexate (MTX) and cytosine arabinoside (Ara-C) was repeated several times. The patient developed flaccid paraplegia 8 months after the beginning of intrathecal administration, and died 4 months later. Autopsy demonstrated extensive transverse necrosis involving the lower thoracic cord and marked vacuolar degeneration of the white matter of the cervical, upper thoracic and lumbo-sacral cord. Focal vacuolar degeneration of the white matter was also noted in the left parietal lobe. Although vacuolar degeneration of the white matter is a common feature in MTX myelopathy, extensive transverse necrosis is rare. In the present case, an overlapping of two mechanisms, that is, injury of vascular endothelial cells and the direct toxic effect of MTX and Ara-C on the white matter, probably played a crucial role in the pathogenesis of severe myelopathy. Because severe myelopathy occurs infrequently, considering the large number of patients receiving the intrathecal administration of MTX, it is possible that a constitutional predisposition or abnormal sensitivity to MTX was involved in the pathogenesis in the present patient.

[Sustained complete remission of intravascular large B-cell lymphoma with recurrent CNS involvement by autologous peripheral blood stem cell transplantation preconditioned with TBC regimen].

Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of extranodal large B-cell lymphoma characterized by the growth of lymphoma cells only within the lumina of small vessels in various organs. IVLBCL is an intractable hematological disease, in particular, the high incidence of central nervous system (CNS) involvement is one of the causes of the poor prognosis of IVLBCL. Autologous stem cell transplantation (ASCT) is an effective therapeutic option for refractory or high-risk aggressive lymphoma. However, it is unknown whether ASCT is an effective treatment for CNS involvement of aggressive lymphoma including IVLBCL. We show a case of a 39-year-old woman with recurrent CNS involvement of IVLBCL receiving autologous peripheral blood stem cell transplantation (auto-PBSCT) preconditioned with high-dose thiotepa, busulfan, cyclophosphamide (TBC regimen). Culture-negative febrile neutropenia developed requiring antimicrobial therapy, but nonhematological adverse effects including stomatitis and neurotoxicity, with grade ≥ 3, were not observed. The patient achieved and has maintained complete remission (CR) for 24 months after TBC/auto-PBSCT and has survived for around 30 months from the diagnosis of the CNS recurrence. The clinical course of this case suggests that auto-PBSCT preconditioned with TBC could be one of the therapeutic options for the treatment of CNS involvement of IVLBCL.