Central Nervous System Myelomatosis Research Articles

Multiple myeloma with dural mater involvement.

Multiple myeloma is an incurable clonal B-cell malignancy which may present with neoplastic monoclonal plasma cells in either bone or soft tissues. Central nervous system (CNS) involvement such as dural myeloma or intraparenchymal infiltration, or with diffuse leptomeningeal involvement, is uncommon. Dural involvement of myeloma without parenchymal or leptomeningeal disease is an even rarer occurrence; therefore there are no established treatment guidelines for CNS myelomatosis. Here we reported a refractory MM patient progressed to dura mater involvement after the induction therapy but showed good response to lenalidomide treatment.

CENTRAL NERVOUS SYSTEM RELAPSE OF MULTIPLE MYELOMA

Multiple myeloma (MM) is a plasma cell disorder primarily involving bone marrow. Extramedullary involvement is less common, with central nervous system (CNS) myelomatosis being a rare entity and such presentation carries extremely dismal prognosis. We present case of a 40 years old male with MM who was initially treated with 6 cycles of Cyclophosphamide, Thalidomide and Dexamethasone resulting in complete response. 2 years later he presented with CNS myelomatosis and scrotal involvement and was initially treated with Bortezomib and dexamethasone, cranial irradiation and intrathecal Methorexate, Cytarabine, Hydrocortisone (TRIO IT), along with radical orchiectomy and testicular radiation during the course of treatment. However, after initial response his disease showed clinical and radiological progression after 4 months of therapy. He was switched to high dose Methotrexate (HD-MTX) with TRIOITand later Lenalidamide and dexamethasone (Len/dex) was added to the above regimen. He continued to show good clinical response but his cytology remained persistently positive, therefore, HD-MTX was discontinued in the later course of treatment. Subsequently he was started on best supportive care only, when his neurological status deteriorated further. He survived almost 9 months after a diagnosis of CNS myelomatosis. Patients with multiple myeloma, presenting with neurological symptoms should always be investigated for the possibility of CNS MM. CNS relapse is a fatal disease with poor prognosis. Recommended treatment must include a systemic anti-MM regimen that crosses the BBB (ideally Immunomodulatory drugs (IMiDs) IMiDs-dexamethasone based therapy), CNS irradiation and intrathecal chemotherapy.Key words: Multiple myeloma, central nervous system myelomatosis, therapy

Initial Presentation Of Multiple Myeloma As Intraparenchymal Brain Mass

Case presentation38 year old African female presented with complaints of severe headache which had started couple of weeks prior to presentation and was progressively becoming worse. Patient underwent a CT scan of the head which revealed a 3.2 X 3.3 X 3.7 cm lobulated hyperdense periventricular mass in the left temporoparietal area with surrounding vasogenic edema with mass effect on the adjacent left lateral ventricle and 0.6 cm midline shift to the right with uncal herniation and effacement of left cerebral peduncle with dilatation of left temporal horn. MRI of the brain revealed a 3.1 X 2.6 X 3.6 cm lobulated mass in left lateral ventricle trigone. Radiologically, differential diagnoses included intraventricular meningioma, lymphoma, choroid plexus papilloma or metastasis. Patient underwent left craniotomy for tumor resection. Patient had an uneventful post-operative recovery and the resected tumor was high grade malignant neoplasm with plasmablastic features and immunohistochemical stains revealed that the tumor cells were positive for CD138, CD30, MUM-1, Bcl-2, vimentin and lambda light chains and were negative for kappa light chains, CD3, CD20, PAX-5, CD79a, GFAP, cytokeratin, AE1/AE3, synaptophysin, chromogranin, EMA, S-100, Melan-A, CD45, CD56 and EBV(EBER-ISH). Ki-67 was about 80%. Serum protein electrophoresis (SPEP) was sent that showed an M-spike of 3.3 g/dl that was IgG lambda. A bone marrow biopsy showed 100 % infiltration with plasma cells. Patient underwent a CT chest/abdomen/pelvis and a PET/CT scan which revealed multiple scattered subcutaneous masses throughout the body and an asymptomatic mass near spinal cord at C1. Patient was treated with VTD-PACE regimen (bortezomib, thalidomide, decadron, cisplatin, liposomal doxorubicin, cyclophosphamide, and etoposide). She received two cycles of VTD-PACE chemotherapy regimen with excellent response to the treatment. Her M-spike protein which prior to treatment was 3.3 g/dl disappeared after second cycle of chemotherapy and her subcutaneous lesion also dramatically improved on repeat PET/CT scan. The C1 dural lesion also had significant improvement after the chemotherapy. Her IgG also decreased from 5070 mg/dl to 791 mg/dl. She was referred for autologus stem cell transplant. She was subsequently started on weekly cyclophosphamide, bortezomib and decadron. DiscussionMalignancies of plasma cells comprise 1% of malignant neoplasms which includes multiple myeloma, solitary plasmacytomas (including solitary bone plasmacytoma and extramedullary plasmacytomas) and immunoglobulin deposition syndromes. Central nervous system (CNS) involvement of multiple myeloma itself is not a common entity. Fassas et al. published data of 18 cases over a course of 10 years. Gozzetti et al. published their data of 50 patients in 2012. Of these 50 patients, 76% had osteo-dural or primary dural multiple myeloma (OD-DMM) and 24% had central nervous system myelomatosis. They found that patients treated with novel agents had better outcome than patients treated with conventional drugs. Cases with initial presentation of intracranial plasmacytomas are even rarer. Patients with CNS myeloma have poor prognosis with median survival being around 4- 5 months. Our patient had excellent response with two cycles of VTD-PACE regimen with negative M-spike, normalization of IgG and decrease in size of subcutaneous nodules and C1 spinal lesion. She has survived for 5 months without autologus transplant and is currently on weekly cyclophosphamide, bortezomib and decadron. Disclosures:No relevant conflicts of interest to declare.

Multiple myeloma invasion of the central nervous system

Multiple myeloma (MM) is characterized by the presence of neoplastic proliferating plasma cells. The tumor is generally restricted to the bone marrow. The most common complications include renal insufficiency, hypercalcemia, anemia and reccurent infections. The spectrum of MM neurological complications is diverse, however, involvement of MM in the cerebrospinal fluid (CSF) and leptomeningeal infiltration are rare considered. In about 1% of the cases, the disease affects the central nervous system (CNS) and presents itself in the form of localized intraparenchymal lesions, solitary cerebral plasmocytoma or CNS myelomatosis (LMM). We presented the clinical course of a 55-year-old man with MM and LMM proven by malignant plasma cells in the CSF, hospitalized with the pain in the thoracic spine. His medical history was uneventful. There had been no evidence of mental or neurological impairment prior to the seizures. Physical examination showed no abnormalities. After a complete staging, the diagnosis of MM type biclonal gammopathia IgG lambda and free lambda light chains in the stage III was confirmed. The treatment started with systemic chemotherapy (with vincristine, doxorubicin plus high-dose dexamethasone--VAD protocol), radiotherapy and bisphosphonate. The patient developed weakness, nausea, febrility, dispnea, bilateral bronchopneumonia, acute renal insufficiency, confusions, headaches and soon thereafter sensomotor aphasias and right hemiparesis. The patient was treated with the adequate therapy including one hemodyalisis. His neurological status was deteriorated, so Multislice Computed Tomography (MSCT) of the head was performed and the findings were normal. Analysis of CSF showed pleocytosis, 26 elements/mL and increased concentrations of proteins. Cytological analysis revealed an increased number of plasma cells (29%). Electrophoretic analysis of proteins disclosed the existance of monoclonal components in the serum, urine and CSF. Immunofixation electrophoretic and quantitative nephelometric tests confirmed Biclonal multiple myeloma of IgG lambda and light chain lambda isotypes. Analysis of neurothropic viruses with ELISA methods was negative. Once the presence of LMM was confirmed, the patient received intrathecal chemotherapy with methotrexate, cytosine arabinoside, dexamethasone three times a week, and systemic high doses of dexamethasone iv like a single agent without craniospinale irradiations. Despite the treatment, the patient died one month after the diagnosis. Autopsy was not performed. Presented patient, as well as most other patients with MM progressing to CN Sinfiltration was in the stage III. In addition to the detailed clinical examination, and all investigations required for MM diagnosis and staging of the disease, we introduced the additional CSF examination and calculation of kappa lambda ratio, that helped us make an early diagnosis and prognosis of MM with LMM. Although LMM had a low prevalence, it could be more frequent than expected especially in patients with high risk. CSF examination with positive plasma cells and abnormal morphology remains the hallmark for diag nosing CNS infiltration.

Extramedullary intracranial localization of multiple myeloma and treatment with novel agents: A retrospective survey of 50 patients

Intracranial involvement in multiple myeloma is extremely rare. The effect of new drugs (eg, thalidomide, bortezomib, lenalidomide) with respect to old drugs (eg, alkylators, steroids) has not been reported. We collected clinical and biological data of patients presenting with an osteo-dural or primary dural multiple myeloma (OD-DMM) or a central nervous system myelomatosis (CNS-MM) by sending a questionnaire to the centers of the Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA). A total of 50 patients were registered. New therapies were used in 35 patients, whereas 15 patients received old treatments. Twenty-five out of 50 patients obtained a complete remission or a very good partial remission (CR+VGPR). Overall survival (OS) for CNS-MM was 6 months, for OD-DMM 25 months. OS was 25 months for patients treated with new agents versus 8 months with old agents. Improved OS and progression-free survival were predicted by response (CR+VGPR) and by patients who underwent stem cell transplantation versus chemotherapy. β2-Microglobulin >5 mmol/L was a poor prognostic factor. Multivariate analysis showed poor survival for patients with β2-microglobulin >5 mmol/L and better survival for patients achieving CR+VGPR. The overall data highlight the relevance of therapy with new drugs in intracranial myeloma, providing a framework for future clinical trials.

Central nervous system myelomatosis with optic neuropathy and intramedullary spinal cord compression responding to radiation therapy

Central nervous system (CNS) involvement by multiple myeloma is a rare complication that occurs in less than 1% of cases. The purpose of this report is to highlight the unique presentation and treatment of a patient with CNS myelomatosis. A 58-year-old Caucasian woman with multiple myeloma developed subacute vision loss bilaterally and was found to have plasma cells in her cerebrospinal fluid. Using a helmet field to 25 Gy in 10 fractions, her vision was stabilized with radiotherapy. After developing right upper extremity numbness and weakness, magnetic resonance imaging revealed intramedullary spinal cord lesions from C5 to C7. She received radiotherapy to 25 Gy in 10 fractions from C4 to T1, with improvement in upper extremity strength after 15 Gy. Although CNS involvement by multiple myeloma is a rare complication, increasing awareness is necessary for clinicians to consider meningeal myelomatosis in patients with this neoplasm.

PET/CT and MR Imaging of Central Nervous System Myelomatosis

Multiple myeloma essentially targets the axial and appendicular skeleton. From the skull and vertebra, the myelomatous lesions may extend to the brain and spinal canal. Extramedullary central nervous system involvement with leptomeningeal and epidural masses is uncommon and usually demonstrated by MR imaging in symptomatic patients. The authors present a case of clinically unexpected central nervous system myelomatosis initially detected by PET/CT and subsequently confirmed by MR.

A Case of Central Nervous System Myelomatosis with Complex Chromosome Aberrations

Involvement of the central nervous system is very uncommon in multiple myeloma, observed in approximately 1% of the multiple myeloma patients. We report a case of central nervous system myelomatosis with complex chromosome aberrations in a 62-yr-old female patient, who had previously been diagnosed as multiple myeloma. Fluorescent in situ hybridization revealed 13q deletion, p53 gene deletion and IGH/FGFR3 rearrangement and chromosomal study showed complex chromosome aberrations. After four cycles of chemotherapy, the patient was admitted to the hematology department with severe headache. Plasma cells were found in the cerebrospinal fluid (CSF), and CSF immunoelectrophoresis revealed abnormal precipitin arcs against anti-IgG and anti-lambda antisera. She was given systemic chemotherapy and eight courses of intrathecal chemotherapy, which cleared plasma cells in the CSF. Two months later, she was given autologous stem cell transplantation. Three months after stem cell transplantation, central nervous system myelomatosis progressed to plasma cell leukemia and two months later, the patient expired.

Intracranial Multifocal Dural Involvement in Multiple Myeloma: Case Report and Review of the Literature

Multiple myeloma is an incurable clonal B-cell malignancy with terminally differentiated plasma cells that accounts for 1% of all malignancies in the United States. It may present with tumors consisting of discrete masses of neoplastic monoclonal plasma cells in either bone or soft tissues. Central nervous system (CNS) involvement of myeloma is uncommon and is observed in approximately 1% of cases. It may manifest as dural myeloma or intraparenchymal infiltration, or with diffuse leptomeningeal involvement. Dural involvement of myeloma without parenchymal or leptomeningeal disease is an even rarer occurrence, with only 5 cases reported in the medical literature. There are no established treatment guidelines for CNS myelomatosis; prognosis and literature on the use of treatment modalities for this complication is reviewed herein.

Central Nervous System and Intracranial Myeloma: a Retrospective Italian Multicenter Study.

Abstract 1882Poster Board I-905 Introduction.Intracranial involvement (IC) in multiple myeloma (MM) is extremely rare, most frequently resulting from osseous lesions in the cranial vault and skull base. Central nervous system (CNS) MM is even rarer (arising in less than 1% of the patients) consisting in intraparenchymal localizations, cerebral plasmacytomas or CNS myelomatosis. Patients described in the literature are few and treatments are variegate: systemic chemotherapy, (CHT), intrathecal therapy, (IT), radiotherapy, (RT) with results being discouraging with median survivals of 1 month or less. The impact of new drugs (thalidomide, bortezomib, lenalidomide) on CNS and IC MM has not been reported. Patients and Methods.We retrospectively collected clinical and biological data of patients presenting with a CNS or IC MM irrespective of disease status (diagnosis, response, relapse) by sending a questionnaire to the GIMEMA (Gruppo Italiano Malattie Ematologiche dell'Adulto) centers. Twelve centers answered. Results.Clinical characteristics. A total of 32 patients (M:F=18:14) were registered. All patients had an IC or CNS MM observed in the period between 2004–2009. Ten patients presented a CNS involvement, while 22 had an IC involvement. 9/32 patients had a CNS /IC involvement at diagnosis (4/5); 23/32 patients has a CNS/IC involvement after a median of 16 months (range 1–104) from MM diagnosis. Median age was 63 years (range 44–83) with no difference in both groups; monoclonal protein was IgG 18 (k16, λ2), IgA 6 (k4, λ2), BJ 6 (k3, λ3), non secretory 2. One patient had a solitary primitive IC plasmacytoma, 1 patient had an extramedullary localization in the lung. β2-microglobulin was available in 23 patients with a median value of 4 (range 1.1–17,5): ≤3.5 in 9 patients; >3.5<5.5 in 8 patients; >5.5 in 6 patients. FISH on bone marrow plasma cells was available in 11/32 patients: 60% of the patients showed genomic abnormalities, the more frequent being in order del 13q, t(11;14), del 17p. The most frequent presenting symptoms were in order headache (30%), confusion (27%), visual disturbances (25%), extremities weakness (21%), cranial nerve palsies (21%), paraesthesias (12%), vertigo (5%), convulsions (4%). Magnetic resonance imaging (MRI) of the brain was the preferred radiological imaging in 23/32 patients; computed tomography (CT) was used in 9/32 patients. Cerebrospinal fluid (CSF) involvement was demonstrated in 5/10 CNS MM. Cytogenetic analysis of cerebrospinal fluid was available in two patients who showed a complex karyotype. Treatment.CHT only was administered to 21 patients, CHT+RT to 5 patients, CHT+RT+IT to 3 patients, RT only to 1 , CHT +IT to 1, RT+IT to 1. Bortezomib was used in 15 patients, Thalidomide in 9, Lenalidomide in 3, MP in 7 , VAD in 3, PAD (with liposomal doxorubicin) in 2, cyclophosphamide in 3, other treatments in 3, and 8 patients received an high dose treatment + stem cells transplant (SCT) (5 Autologous/ 3 Allogeneic). 18/32 patients had a response after treatment defined as at least a reduction of 50% of the mass and /or M component (13 CR+VGPR) ; 17 patients had symptoms disappearance. PFS was at a median of 5 months (range 1–36). Median OS for CNS MM was 5 months (range 1–23), OS for IC MM was 9 months (range 1–42). 5/10 patients with CNS MM died at a median of 2 months (1–6); while 13/22 IC MM died at median of 8 months (1–46). 14/32 patients are alive at the present time (5 CNS, 9 IC). Interestingly, of 5 CNS MM patients alive 1 had AutoSCT , 4 received Bortezomib (1 combined with MP, 2 with liposomal doxorubicin, 1 with thalidomide); while of the 9 IC MM alive 3 received Bortezomib, 3 Auto SCT, 1 thalidomide, 1 lenalidomide, 1 cyclophosphamide. β2-microglobulin > 5.5 was a poor prognostic factor, as well as age >65 years. Conclusions.High dose therapies followed by autologous SCT seem to be the preferable therapy for eligible young patients. Novel drugs such as bortezomib, thalidomide, lenalidomide seem to increase the quality of responses and to prolong survival respect to what reported in the literature. Largest prospective studies are needed to confirm these findings. Disclosures:Petrucci:celgene: Honoraria; Jansenn-cilag: Honoraria. Palumbo:CELGENE: Honoraria.

A Case of Central Nervous System Myelomatosis Developing after Allogeneic Hematopoietic Stem Cell Transplantation

Central nervous system (CNS) myelomatosis, which is the presence of monoclonal plasma cells in the cerebrospinal fluid (CSF), is extremely rare. We report a case of CNS myelomatosis developed in a 45-year-old woman with multiple myeloma in complete response, which was achieved by allogeneic pe- ripheral blood stem cell transplantation using a reduced-intensity conditioning regimen consisting of mel- phalan, fludarabine, and antithymocyte globulin. Two months aft er the transplant, she developed a moder- ate motor and sensory weakness in both lower extremities. Atypical plasma cells were found in the CSF, and immunofixation revealed monoclonal light chain in the CSF. She was given three courses of weekly intra-thecal chemotherapy consisting of methotrexate, cytarabine, and dexamethasone, which cleared the CSF. This case indicates that the allogeneic transplantation could not control CNS myelomatosis, despite successfully treating the bone marrow myeloma. (Korean J Hematol 2008;43:194-197.)

Central nervous system myelomatosis: review of the literature

Involvement of the central nervous system (CNS) in multiple myeloma (MM) is very uncommon; it has been observed in approximately 1% of the MM patients. This review summarizes the clinical and laboratory characteristics and treatment modalities of 109 patients with CNS myelomatosis (CNS MM) reported in the literature. CNS MM has a wide spectrum of neurological symptoms and signs. No guidelines for therapy of CNS MM are available, which has resulted in a large variation in the treatment schedules. Treatment options include intrathecal chemotherapy (IT), systemic chemotherapy (SC), cranial irradiation (CI) or a combination. The prognosis of CNS MM remains poor, with an overall median survival from the time of diagnosis to death of 2.0 months (range 0.1-25 months). Patients who were treated with CI had a significantly (P = 0.004) longer survival when compared with patients without CI.