mycophenolic-acid and Lymphoma--Large-B-Cell--Diffuse

A 41-year-old woman with a 14-month history of systemic lupus erythematosus (SLE) presented with headache, aphasia, and agraphia. A laboratory examination revealed mild proteinuria, hypocomplementemia, and elevated anti-double-stranded DNA antibody levels. A cerebrospinal fluid analysis demonstrated elevated protein and interleukin-6 levels. Magnetic resonance imaging (MRI) of the brain identified multiple lesions suggestive of brain edemas and small haemorrhages. She was diagnosed as having neuropsychiatric lupus and lupus nephritis and received remission induction therapy with high-dose corticosteroid and intravenous cyclophosphamide. She achieved a complete remission, and treatment with mycophenolate mofetil (MMF) was initiated 3 months thereafter for remission maintenance. At 13 months after the exacerbation of SLE, she complained of headache and nausea. A gadolinium-enhanced MRI of the brain revealed a low-signal-intensity tumour with marginal ring enhancement of 50 mm in the left frontal lobe. The tumour was excised, and the histological diagnosis was diffuse large B-cell lymphoma with positive Epstein-Barr virus (EBV). MMF was discontinued. Remission induction therapy with rituximab, high-dose methotrexate, procarbazine, and vincristine was administered, and she achieved remission. Previous reports suggest that use of MMF is associated with primary central nervous system (CNS) lymphoma (PCNSL) in patients with lupus nephritis or other autoimmune diseases or in post-transplant patients. Our observation that PCNSL occurred after CNS involvement of SLE suggests that EBV and CNS inflammation arising from SLE might have contributed to the development of PCNSL.

Topics: Adult; Antibodies, Antinuclear; Central Nervous System; Epstein-Barr Virus Infections; Female; Herpesvirus 4, Human; Humans; Lupus Vasculitis, Central Nervous System; Lymphoma, Large B-Cell, Diffuse; Mycophenolic Acid

Primary central nervous system lymphoma (PCNSL) is a rare form of extranodal non-Hodgkin lymphoma and four cases of PCNSL have previously been described in association with mycophenolate mofetil. We report the fifth case of PCNSL in a patient with lupus nephropathy while on mycophenolate mofetil treatment.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Central Nervous System Neoplasms; Diffusion Magnetic Resonance Imaging; Fatal Outcome; Female; Humans; Immunocompromised Host; Immunohistochemistry; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Lymphoma, Large B-Cell, Diffuse; Middle Aged; Mycophenolic Acid; Treatment Outcome; Young Adult

Nonmyeloablative hematopoietic cell transplantation (HCT) has been used to treat patients with advanced or high-risk lymphoid malignancies. We studied 65 patients (median age 46 years) receiving an umbilical cord blood (UCB) graft after a single conditioning regimen consisting of cyclophosphamide (50 mg/kg) on day -6, fludarabine (40 mg/m(2)) daily on days -6 to -2, as well as a single fraction of total-body irradiation (TBI) (200 cGy) along with cyclosporine mycophenolate mofetil immunosuppression. Median time to neutrophil and platelet recovery was 7.5 days (range: 0-32) and 46 days (range: 8-111), respectively. Cumulative incidences of grade II-IV, grade III-IV acute, and chronic graft-versus-host disease (aGVHD, cGVHD) were 57% (95% confidence interval [CI]: 43%-70%), 25% (95% CI: 14%-35%), and 19% (95% CI: 9%-29%), respectively. Transplant-related mortality at 3 years was 15% (95% CI: 5%-26%). Median follow-up was 23 months. The progression free-survival (PFS), current PFS and overall survival (OS) were 34% (95% CI: 21%-47%), 49% (95% CI: 36%-62%), and 55% (95% CI: 42%-70%) at 3 years. Based on our data, we conclude that a nonmyeloablative conditioning regimen followed by UCB transplantation is an effective treatment for patients with advanced lymphoid malignancies who lack a suitable sibling donor.

Topics: Adolescent; Adult; Aged; Child; Cord Blood Stem Cell Transplantation; Cyclophosphamide; Cyclosporine; Disease-Free Survival; Female; Humans; Immunosuppression Therapy; Lymphoma, Follicular; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Middle Aged; Mycophenolic Acid; Survival Analysis; Transplantation Conditioning; Vidarabine; Whole-Body Irradiation; Young Adult

A 76-year-old woman with dermatomyositis was being treated with prednisolone, tacrolimus, and mycophenolate mofetil. There was a solitary lung nodule in the right middle lobe on chest computed tomography at a routine follow-up examination. A transbronchial lung biopsy was performed, and the histopathologic findings indicated diffuse large B-cell lymphoma. An immunodeficiency-associated lymphoproliferative disorder was suspected, and mycophenolate mofetil was stopped without adding any other therapy. Nine months later, the pulmonary nodule had disappeared on chest computed tomography.

Topics: Aged; Female; Humans; Lung; Lymphoma, Large B-Cell, Diffuse; Mycophenolic Acid; Solitary Pulmonary Nodule; Tacrolimus

Epstein Barr virus (EBV)-associated primary central nervous system lymphoma (ePCNSL) is increasingly recognized in immunocompromised subjects, including patients receiving systemic immunosuppressive therapy. Here, we report the first case of primary CNS lymphoma associated with EBV in a patient with diffuse cutaneous systemic sclerosis (dcSSc) receiving long-term mycophenolate mofetil (MMF).. A 51-year-old female with dcSSc had been on MMF 2 grams daily, which was initiated for a rapidly rising modified Rodnan skin score (mRSS), severe pruritus, and progressive joint contractures. She had an impressive response to this therapy with a significant decrease in her mRSS. Her condition remained stable for the next five years, after which she developed worsening headaches for 2-3 weeks, associated with dizziness, gait instability, and left homonymous hemianopia. MRI scan of the brain revealed a solitary 2.4cm peripherally enhancing right parietal lobe mass. Excised tissue from the right parietal lobe mass showed EBV-associated diffuse large B cell lymphoma. She received four cycles of chemotherapy (high dose methotrexate and rituximab). Currently, her condition is being monitored. Her left homonymous hemianopia persists.. Because of a favorable toxicity profile, MMF is increasingly being used as long-term immunomodulatory therapy for a wide variety of autoimmune disorders. Nevertheless, patients on long-term MMF should still undergo regular CNS surveillance, not only for opportunistic infections but also for opportunistic malignancies such as PCNSL. Progressive focal or non-focal neurological deficits should always raise the alarm. Prompt evaluation and management can prevent irreversible neurological sequelae.

Topics: Central Nervous System; Epstein-Barr Virus Infections; Female; Herpesvirus 4, Human; Humans; Lymphoma, Large B-Cell, Diffuse; Middle Aged; Mycophenolic Acid; Scleroderma, Diffuse

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Topics: Antibiotics, Antineoplastic; Biopsy; Echocardiography; Heart Neoplasms; Heart Transplantation; Humans; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Mycophenolic Acid; Pericardium; Positron-Emission Tomography; Ultrasonography

Patients with systemic lupus erythematosus (SLE) are susceptible to the development of lymphoproliferative disorders and postulated causes include intrinsic defects in immune surveillance and iatrogenic administration of immunosuppressants. Since the introduction of mycophenolate mofetil (MMF) to the immunosuppressive regimen for the management of post-organ transplantation, there have been reports of primary lymphoma of the central nervous system (PCNSL). MMF has been widely used to treat active SLE patients with Class IV lupus nephritis. In addition to two previously reported cases of PCNSL among SLE patients on long-term MMF, we report a third patient who has been on treatment with MMF for 8 years. The histology showed features compatible with diffuse large B-cell lymphoma with strong immunohistochemical staining for CD20 and positive signal for Epstein-Barr virus (EBV)-encoded RNA by in-situ hybridization that is similar to other case reports, suggesting EBV driven B-cell lymphoproliferative disease. The patient responded to withdrawal of MMF, intravenous methotrexate, rituximab and whole brain radiotherapy. With the increasing use of MMF in active renal as well as non-renal exacerbations of SLE, PCNSL should be included in the differential diagnosis in patients who present with gradual onset of focal neurological deficit.

Topics: Adult; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antimetabolites, Antineoplastic; Antineoplastic Agents; Central Nervous System Neoplasms; Epstein-Barr Virus Infections; Female; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Lymphoma, Large B-Cell, Diffuse; Methotrexate; Mycophenolic Acid; Rituximab

Topics: Antilymphocyte Serum; Brain Neoplasms; Cytomegalovirus Retinitis; Epstein-Barr Virus Infections; Female; Ganciclovir; Graft Rejection; Herpesvirus 4, Human; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Neoplasms; Kidney Transplantation; Lymphoma, Large B-Cell, Diffuse; Middle Aged; Muromonab-CD3; Mycophenolic Acid; Postoperative Complications; Prednisolone; Radiography; RNA, Viral; Tacrolimus; Transplantation, Homologous

Topics: Administration, Oral; Adult; Aged; Antibiotics, Antineoplastic; Caproates; Carcinoma; Esophageal Neoplasms; Female; Hodgkin Disease; Humans; Injections, Intraperitoneal; Injections, Intravenous; Leukemia, Lymphoid; Leukemia, Myeloid; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Multiple Myeloma; Mycophenolic Acid; Stomach Neoplasms