SLE Patients at High Risk for Non-Hodgkin's, Other Cancers

SORRENTO, ITALY — Patients with systemic lupus erythematosus are at high risk for the development of certain types of malignancy, particularly non-Hodgkin's lymphoma and cervical cancer, Dr. Emese Kiss said at the Fifth International Congress on Autoimmunity.

Improved treatments have resulted in greater life expectancy among patients with lupus, with the unintended consequence that morbidity and mortality from causes other than lupus itself have assumed increasing importance.

A retrospective analysis of data from 860 patients seen between 1970 and 2004 identified 37 cases of cancer, for an overall prevalence of 4.3%, reported Dr. Kiss of the University of Debrecen (Hungary).

When compared with age- and sex-matched controls, the resulting standardized incidence ratio for all cancers of 0.85 was not elevated, she said.

But the standardized incidence ratios for cervical cancer, hematologic malignancies, and non-Hodgkin's lymphoma were 1.74, 1.31, and 3.47, respectively.

The highest relative risks were 4.6 for non-Hodgkin's lymphoma and 2.3 for cervical cancer, she said.

During the study period 164 patients died, 18 of malignancies, for a cancer-related mortality of 11%.

In most other surveys of cancer among patients with lupus, elevated risks have been reported for lung, hepatobiliary, and hematologic malignancies. Some studies also have found increased frequency of breast, gynecologic, bladder, and prostate cancer, depending on age, race, and gender distribution.

Among the postulated reasons for the increased lymphoma risk in lupus patients are high inflammatory activity and uncontrolled B-cell proliferation, which increase the risk of oncogene translocations, Dr. Kiss explained in an interview.

Diffuse, large B-cell lymphomas that are derived primarily from peripheral activated B cells are the major types of lymphoma in patients with lupus as well as in those with rheumatoid arthritis. This can be considered indirect evidence supporting the role of inflammation and disease activity in the development of non-Hodgkin's lymphoma, she said.

The use of immune modulatory agents in treatment also may contribute, either by direct mutagenesis or by disturbing immune surveillance and thus allowing dysregulated proliferation of B cells, she said.

Another contributing factor may be the fact that lupus and non-Hodgkin's lymphoma share some clinical manifestations, including thrombocytopenia, leucopenia, anemia, lymphadenopathy, and hepatosplenomegaly. This may complicate and delay the diagnosis of non-Hodgkin's lymphoma.

The elevated risk for cervical cancer may relate to increased rates of infection with human papillomavirus or to impaired clearance of the virus. It also may be associated with the use of cytostatic drugs, although a direct association between human papillomavirus infection and treatment with cyclophosphamide or azathioprine could not be confirmed, Dr. Kiss said.

An important implication of these data is that increased attention must be paid to screening for these cancers, such as with Pap testing, she said.

An additional “surprising” finding in this analysis was that the malignant disorders appeared not as late complications, but most often within the first 5–10 years after the onset of lupus. “This suggests that immune suppressive therapy is not the only factor increasing cancer risk, and again supports the importance of high disease activity in the development of cancer,” she said.

The mean age at the onset of malignancy was 47 years. The earliest malignancies to develop were the hematologic and hepatobiliary cancers, while colorectal and gastric cancers appeared much later, sometimes more than 20 years after the diagnosis of systemic lupus erythematosus, Dr. Kiss said. Half of lupus patients do not survive long enough to develop gastrointestinal cancers, she said.

SORRENTO, ITALY — Patients with systemic lupus erythematosus are at high risk for the development of certain types of malignancy, particularly non-Hodgkin's lymphoma and cervical cancer, Dr. Emese Kiss said at the Fifth International Congress on Autoimmunity.

Improved treatments have resulted in greater life expectancy among patients with lupus, with the unintended consequence that morbidity and mortality from causes other than lupus itself have assumed increasing importance.

A retrospective analysis of data from 860 patients seen between 1970 and 2004 identified 37 cases of cancer, for an overall prevalence of 4.3%, reported Dr. Kiss of the University of Debrecen (Hungary).

When compared with age- and sex-matched controls, the resulting standardized incidence ratio for all cancers of 0.85 was not elevated, she said.

But the standardized incidence ratios for cervical cancer, hematologic malignancies, and non-Hodgkin's lymphoma were 1.74, 1.31, and 3.47, respectively.

The highest relative risks were 4.6 for non-Hodgkin's lymphoma and 2.3 for cervical cancer, she said.

During the study period 164 patients died, 18 of malignancies, for a cancer-related mortality of 11%.

In most other surveys of cancer among patients with lupus, elevated risks have been reported for lung, hepatobiliary, and hematologic malignancies. Some studies also have found increased frequency of breast, gynecologic, bladder, and prostate cancer, depending on age, race, and gender distribution.

Among the postulated reasons for the increased lymphoma risk in lupus patients are high inflammatory activity and uncontrolled B-cell proliferation, which increase the risk of oncogene translocations, Dr. Kiss explained in an interview.

Diffuse, large B-cell lymphomas that are derived primarily from peripheral activated B cells are the major types of lymphoma in patients with lupus as well as in those with rheumatoid arthritis. This can be considered indirect evidence supporting the role of inflammation and disease activity in the development of non-Hodgkin's lymphoma, she said.

The use of immune modulatory agents in treatment also may contribute, either by direct mutagenesis or by disturbing immune surveillance and thus allowing dysregulated proliferation of B cells, she said.

Another contributing factor may be the fact that lupus and non-Hodgkin's lymphoma share some clinical manifestations, including thrombocytopenia, leucopenia, anemia, lymphadenopathy, and hepatosplenomegaly. This may complicate and delay the diagnosis of non-Hodgkin's lymphoma.

The elevated risk for cervical cancer may relate to increased rates of infection with human papillomavirus or to impaired clearance of the virus. It also may be associated with the use of cytostatic drugs, although a direct association between human papillomavirus infection and treatment with cyclophosphamide or azathioprine could not be confirmed, Dr. Kiss said.

An important implication of these data is that increased attention must be paid to screening for these cancers, such as with Pap testing, she said.

An additional “surprising” finding in this analysis was that the malignant disorders appeared not as late complications, but most often within the first 5–10 years after the onset of lupus. “This suggests that immune suppressive therapy is not the only factor increasing cancer risk, and again supports the importance of high disease activity in the development of cancer,” she said.

The mean age at the onset of malignancy was 47 years. The earliest malignancies to develop were the hematologic and hepatobiliary cancers, while colorectal and gastric cancers appeared much later, sometimes more than 20 years after the diagnosis of systemic lupus erythematosus, Dr. Kiss said. Half of lupus patients do not survive long enough to develop gastrointestinal cancers, she said.

SORRENTO, ITALY — Patients with systemic lupus erythematosus are at high risk for the development of certain types of malignancy, particularly non-Hodgkin's lymphoma and cervical cancer, Dr. Emese Kiss said at the Fifth International Congress on Autoimmunity.

Improved treatments have resulted in greater life expectancy among patients with lupus, with the unintended consequence that morbidity and mortality from causes other than lupus itself have assumed increasing importance.

A retrospective analysis of data from 860 patients seen between 1970 and 2004 identified 37 cases of cancer, for an overall prevalence of 4.3%, reported Dr. Kiss of the University of Debrecen (Hungary).

When compared with age- and sex-matched controls, the resulting standardized incidence ratio for all cancers of 0.85 was not elevated, she said.

But the standardized incidence ratios for cervical cancer, hematologic malignancies, and non-Hodgkin's lymphoma were 1.74, 1.31, and 3.47, respectively.

The highest relative risks were 4.6 for non-Hodgkin's lymphoma and 2.3 for cervical cancer, she said.

During the study period 164 patients died, 18 of malignancies, for a cancer-related mortality of 11%.

In most other surveys of cancer among patients with lupus, elevated risks have been reported for lung, hepatobiliary, and hematologic malignancies. Some studies also have found increased frequency of breast, gynecologic, bladder, and prostate cancer, depending on age, race, and gender distribution.

Among the postulated reasons for the increased lymphoma risk in lupus patients are high inflammatory activity and uncontrolled B-cell proliferation, which increase the risk of oncogene translocations, Dr. Kiss explained in an interview.

Diffuse, large B-cell lymphomas that are derived primarily from peripheral activated B cells are the major types of lymphoma in patients with lupus as well as in those with rheumatoid arthritis. This can be considered indirect evidence supporting the role of inflammation and disease activity in the development of non-Hodgkin's lymphoma, she said.

The use of immune modulatory agents in treatment also may contribute, either by direct mutagenesis or by disturbing immune surveillance and thus allowing dysregulated proliferation of B cells, she said.

Another contributing factor may be the fact that lupus and non-Hodgkin's lymphoma share some clinical manifestations, including thrombocytopenia, leucopenia, anemia, lymphadenopathy, and hepatosplenomegaly. This may complicate and delay the diagnosis of non-Hodgkin's lymphoma.

The elevated risk for cervical cancer may relate to increased rates of infection with human papillomavirus or to impaired clearance of the virus. It also may be associated with the use of cytostatic drugs, although a direct association between human papillomavirus infection and treatment with cyclophosphamide or azathioprine could not be confirmed, Dr. Kiss said.

An important implication of these data is that increased attention must be paid to screening for these cancers, such as with Pap testing, she said.

An additional “surprising” finding in this analysis was that the malignant disorders appeared not as late complications, but most often within the first 5–10 years after the onset of lupus. “This suggests that immune suppressive therapy is not the only factor increasing cancer risk, and again supports the importance of high disease activity in the development of cancer,” she said.

The mean age at the onset of malignancy was 47 years. The earliest malignancies to develop were the hematologic and hepatobiliary cancers, while colorectal and gastric cancers appeared much later, sometimes more than 20 years after the diagnosis of systemic lupus erythematosus, Dr. Kiss said. Half of lupus patients do not survive long enough to develop gastrointestinal cancers, she said.