Meningeal myelomatosis developed after treatment with novel agents

Abstract

A 66-year-old woman was diagnosed in March 2007 with Bence-Jones protein-lambda positive (BJP k) multiple myeloma. After four cycles of bortezomib and dexamethasone, complete response was achieved in 2009. Radiotherapy was performed for skull and spine lesions in 2010 and 2011. She remained in stable disease with disappearance of M protein and bone marrow plasma cells on maintenance therapy with bortezomib, thalidomide, and dexamethasone. However, in May 2012, serum LDH began to elevate and multiple subcutaneous plasmacytoma appeared. Subcutaneous tumors increased following administration of lenalidomide and dexamethasone. Bone marrow examination in September 2012 demonstrated 50.8 % plasma cells. Cytogenetic analysis revealed a complex karyotype including chromosome 13 deletion and t(8;14)(q24;q32) in 19 of 20 metaphase cells. Although VCAP (vincristine, cyclophosphamide, doxorubicin, and prednisolone) slightly decreased subcutaneous tumors, she complained of headache, pain in the neck, dizziness, nausea, and vomiting in February 2013. Laboratory studies showed serum protein 6.2 g/dL, LDH 711 IU/L (normal range 80–200 IU/L), b2 microglobulin 2.5 mg/L, free light chain (FLC) j\ 0.6 mg/L (3.3–19.4 mg/L), k 269.0 mg/L (5.7–26.3 mg/L), and urine M protein 118 mg/24 h. Brain magnetic resonance imaging demonstrated meningeal contrast enhancement, particularly in the posterior fossa (Fig. 1). A lumbar puncture revealed a cerebrospinal fluid (CSF) protein of 48 mg/dL (10–53 mg/dL) and a marked pleocytosis of 300 cells/lL. The CSF cytology showed numerous plasma cells with prominent nucleoli (Fig. 2). FLC assay of the CSF demonstrated k chain restriction: j\ 0.6 mg/L, and k 435.0 mg/L. A diagnosis of meningeal myelomatosis was made. No plasma cells were identified in the peripheral blood. The patient received intrathecal chemotherapy of methotrexate and dexamethasone with no response, and died 1 month after the diagnosis. Meningeal myelomatosis, defined by the presence of monoclonal plasma cells in the CSF, is extremely rare and accounts for approximately 1 % of myeloma patients. Previous reports suggest an association of meningeal myelomatosis with extramedullary disease, plasmablastic morphology, cytogenetic abnormalities, high LDH levels, and circulating plasma cells. These are characteristics of aggressive myeloma, some of which we confirmed in our patient. Meningeal myelomatosis occurs as a terminal event in the majority of patients. The prognosis remains poor despite aggressive local and systemic treatment, including stem cell transplantation, with a median overall survival of only a few months. Recently, investigators have showed that the novel agents, thalidomide and lenalidomide, cross the blood–brain barrier and are effective for the management of meningeal myelomatosis [1–3]. However, our patient developed meningeal myelomatosis after receiving these same agents. Cerebral symptoms are commonly seen in terminal-stage myeloma patients from hypercalcemia, uremia, hyperviscosity syndrome, or toxicity of treatment. Physicians should be alert to the possibility of meningeal myelomatosis. The FLC assay of CSF will be helpful for diagnosis even when the CSF cell count and protein level are not elevated. To our knowledge, this is the first report of the use of FLC assay of CSF for diagnosis of meningeal myelomatosis. M. Ise (&) C. Sakai K. Kumagai Department of Hematology-Oncology, Chiba Cancer Center, 666-2 Nitona-cho, Chuo-ku, Chiba, Chiba 260-8717, Japan e-mail: mise@chiba-cc.jp