Clues on the lupus-lymphoma link sought in three case studies

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Chicago researchers looked at three people who developed lymphoma at different stages of their lupus disease to try to find clues about the association between the conditions.

Their study, which involved patients with lupus and non-Hodgkin lymphoma, or NHL, included a number of observations from scientific papers on the link between the diseases.

The research, “SLE and non-Hodgkin lymphoma: a case series and review of the literature, »Appeared in the newspaper Rheumatology case reports. SLE refers to systemic lupus erythematosus, the scientific name for lupus.

There are many manifestations of lupus, some resulting from the disease itself and others from treatment-induced side effects. Studies indicate that patients with lupus have a higher rate of lymphoma than healthy people. This discovery led to research on predictors of lymphoma development, the effect of lymphoma on the prognosis of patients with lupus, and treatment strategies for people with both diseases.

Winston Sequeira, a rheumatologist at Rush University Medical Center in Chicago, and some of his colleagues examined three lupus patients who developed NHL in different stages of their lupus for clues about the disease association. They hoped to identify factors that might contribute to the development of lupus and predictors of that development.

Case 1 involved a woman who had suffered from lupus for 10 years and chronic hepatitis B. She developed primary central nervous system lymphoma, or PCNSL.

Doctors gave her radiation therapy and intravenous dexamethasone. Biopsies of her spine and bone marrow showed the treatment reduced her lymphoma.

The medical team then treated her with high-dose methotrexate, Rituxan (rituximab) and intrathecal methotrexate given to the spinal cord. This three-month chemotherapy combo also improved her condition. Doctors then gave her localized radiation therapy and consolidation chemotherapy with Cytosar-U (cytarabine).

It continues to progress after the multiple treatment regimens.

Case 2 involved a woman who had suffered from lupus for 19 years and who had developed localized lymphoma of the central nervous system, or CNS.

Doctors gave her the immunosuppressants Cytoxan (cyclophosphamide) and CellCept (mycophenolate). They added allopurinol to the diet to treat a complication known as tumor lysis.

They also put her on high-dose intravenous methotrexate for diffuse large B-cell lymphoma, or DLBCL, and Diflucan (fluconazole) for a fungal disease she developed, known as cryptococcosis.

The neurological symptoms she had before her treatment started to improve after her cycle of therapy.

Case 3 involved a man with lupus and LDGCB. Complications arose during her first cycle of chemotherapy. He developed febrile neutropenia, or a low number of immune cells called neutrophils, and his kidney disease progressed to the point that she had to undergo dialysis.

Subsequent cycles of chemotherapy caused the lymphoma to go into remission.

Scientists say lupus stems from problems with regulating the immune system. Some research indicates that immunosuppressants increase a person’s risk of developing lymphoma, although other studies contradict this finding. Research has also suggested an association between immunosuppressants and other types of cancer, although the link is more pronounced in NHL.

PCNSL carries a worse prognosis than other lymphomas. Studies have shown that immunodeficiency and autoimmune diseases are associated with the onset of PCNSL. Case 1 confirmed the finding from previous studies that hepatitis B increases the risk of developing PCNSL, the Chicago researchers said.

Cases 2 and 3 confirmed earlier findings by researchers that DLBCL is the most common type of non-Hodgkin lymphoma in people with lupus.

There are three types of DLBCL. Everyone develops differently, and patients’ responses to treatment and prognosis differ.

Some researchers have suggested a link between the Epstein Barr virus and the development of lymphoma in patients with lupus. The prognosis for non-Hodgkin’s lymphoma in lupus patients “depends heavily on the stage of the disease, with a higher stage predicting” a worse outcome, the Chicago researchers noted.

The standard treatment regimen for DLBCL generally leads to remission of the lymphoma, the researchers said. But it is ineffective in PCNSL because it has difficulty penetrating the blood-brain barrier, they added.

As in Case 1, intrathecal chemotherapy with methotrexate and Rituxan is the standard regimen for the treatment of PCSNL, the team said. But “the potential of stem cell transplantation to play a potentially curative role not only in the management of DLBCL but also to induce prolonged serologic remissions from autoimmune diseases should be explored in future studies,” they wrote.

José is a science journalist with a doctorate in neuroscience from the University of Porto, Portugal. He also studied biochemistry at the Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, New York, and the University of Western Ontario in London, Ontario, Canada. His work ranges from the association of central cardiovascular control and pain with the neurobiological basis of hypertension and the molecular pathways that cause Alzheimer’s disease.

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