Immunoglobulin Test May Signal Cancer Risk

ATLANTA — Healthy blood donors with positive direct antiglobulin tests develop cancer more than twice as often as those who test negative, according to a provocative study that linked thousands of blood bank records to Israel's national cancer registry.

Absolute cancer risk was small in the study: Of people with positive direct antiglobulin tests (DATs), 2.9% developed cancer, compared with 1.2% of DAT-negative donors, Dr. Ora Paltiel reported in a poster at the annual meeting of the American Society of Hematology.

Relative cancer risk was high, however, with hazard ratios of 2.46 overall, 14.20 for hematopoietic cancers, and 8.02 for lymphomas. Even when the investigators excluded cases diagnosed within 12 months of blood donation, people with positive DAT tests had an eightfold higher risk of developing a hematopoietic cancer at an average follow-up of 66 months.

“In a small minority of people, a positive DAT is actually a marker—not a risk factor, a marker—that they have some cancer growing,” said Dr. Paltiel, a hematologist and epidemiologist at the Hadassah University Medical Center, Jerusalem.

“Practically, you would not want to bring a panic because of this, but there are implications to a positive DAT,” she said, urging additional studies to confirm the finding and determine whether DAT testing could help detect early cancers in healthy people.

The DAT test (also known as a direct Coombs' test) has been used since the 1950s to see whether the donor has immunoglobulin antibodies attached to red blood cells, according to Dr. Paltiel. It is not universally required of blood donors, but a positive finding can suggest an immune reaction to a disease process.

The investigators identified 586 blood donors who had positive DAT screens during the years 1993–2003, and matched them by gender, age, and year of blood donation to 2,344 DAT-negative donors. Using unique identification numbers, the study was able to determine cancer incidence through July 30, 2006, in both cohorts. Men made up 63% of the population. The DAT-positive donors were slightly older (34.5 years vs. 32 years on average).

All told, 17 DAT-positive donors and 27 DAT-negative donors developed cancer by mid-2006. Dr. Paltiel said that DAT-positive patients tended to be diagnosed with cancer earlier than those who were DAT negative, perhaps because they had a physical exam after receiving letters notifying them of the DAT results. Three DAT-positive donors were diagnosed with hematopoietic cancers (Hodgkin's lymphoma, non-Hodgkin's lymphoma, and multiple myeloma) during the first year.

The investigators did a subset analysis excluding early diagnoses in people who may have had undiagnosed cancers at the time of blood donation. Looking just at DAT-positive donors diagnosed with cancers after 12 months, the most common malignancies (with two in each category) were lymphoma, multiple myeloma, and thyroid, prostate, and gastrointestinal tumors.

Comparisons of observed cases of cancer in blood donors with expected cases in the general population also found twice the incidence of cancer in DAT-positive donors, but no elevation of cancer rates in those who had tested DAT negative. Incidence of hematologic malignancies was 11-fold higher in the DAT-positive donors, according to the poster. This reflected somewhat increased rates of lymphomas and Hodgkin's lymphoma and a more than 40-fold hike in incidence of multiple myeloma, compared with expected rates.

The increase in a condition as rare as multiple myeloma cannot simply be attributed to more people being screened after a positive DAT test, Dr. Paltiel said. “Some of it has to do with health behavior, but you can't blame myeloma on health behavior.” If a positive DAT leads to earlier diagnosis, she added, the person could benefit from recent advances in treatment of multiple myeloma.

'A positive DAT is actually a marker—not a risk factor, a marker—that they have some cancer growing.' DR. PALTIEL

ATLANTA — Healthy blood donors with positive direct antiglobulin tests develop cancer more than twice as often as those who test negative, according to a provocative study that linked thousands of blood bank records to Israel's national cancer registry.

Absolute cancer risk was small in the study: Of people with positive direct antiglobulin tests (DATs), 2.9% developed cancer, compared with 1.2% of DAT-negative donors, Dr. Ora Paltiel reported in a poster at the annual meeting of the American Society of Hematology.

Relative cancer risk was high, however, with hazard ratios of 2.46 overall, 14.20 for hematopoietic cancers, and 8.02 for lymphomas. Even when the investigators excluded cases diagnosed within 12 months of blood donation, people with positive DAT tests had an eightfold higher risk of developing a hematopoietic cancer at an average follow-up of 66 months.

“In a small minority of people, a positive DAT is actually a marker—not a risk factor, a marker—that they have some cancer growing,” said Dr. Paltiel, a hematologist and epidemiologist at the Hadassah University Medical Center, Jerusalem.

“Practically, you would not want to bring a panic because of this, but there are implications to a positive DAT,” she said, urging additional studies to confirm the finding and determine whether DAT testing could help detect early cancers in healthy people.

The DAT test (also known as a direct Coombs' test) has been used since the 1950s to see whether the donor has immunoglobulin antibodies attached to red blood cells, according to Dr. Paltiel. It is not universally required of blood donors, but a positive finding can suggest an immune reaction to a disease process.

The investigators identified 586 blood donors who had positive DAT screens during the years 1993–2003, and matched them by gender, age, and year of blood donation to 2,344 DAT-negative donors. Using unique identification numbers, the study was able to determine cancer incidence through July 30, 2006, in both cohorts. Men made up 63% of the population. The DAT-positive donors were slightly older (34.5 years vs. 32 years on average).

All told, 17 DAT-positive donors and 27 DAT-negative donors developed cancer by mid-2006. Dr. Paltiel said that DAT-positive patients tended to be diagnosed with cancer earlier than those who were DAT negative, perhaps because they had a physical exam after receiving letters notifying them of the DAT results. Three DAT-positive donors were diagnosed with hematopoietic cancers (Hodgkin's lymphoma, non-Hodgkin's lymphoma, and multiple myeloma) during the first year.

The investigators did a subset analysis excluding early diagnoses in people who may have had undiagnosed cancers at the time of blood donation. Looking just at DAT-positive donors diagnosed with cancers after 12 months, the most common malignancies (with two in each category) were lymphoma, multiple myeloma, and thyroid, prostate, and gastrointestinal tumors.

Comparisons of observed cases of cancer in blood donors with expected cases in the general population also found twice the incidence of cancer in DAT-positive donors, but no elevation of cancer rates in those who had tested DAT negative. Incidence of hematologic malignancies was 11-fold higher in the DAT-positive donors, according to the poster. This reflected somewhat increased rates of lymphomas and Hodgkin's lymphoma and a more than 40-fold hike in incidence of multiple myeloma, compared with expected rates.

The increase in a condition as rare as multiple myeloma cannot simply be attributed to more people being screened after a positive DAT test, Dr. Paltiel said. “Some of it has to do with health behavior, but you can't blame myeloma on health behavior.” If a positive DAT leads to earlier diagnosis, she added, the person could benefit from recent advances in treatment of multiple myeloma.

'A positive DAT is actually a marker—not a risk factor, a marker—that they have some cancer growing.' DR. PALTIEL

ATLANTA — Healthy blood donors with positive direct antiglobulin tests develop cancer more than twice as often as those who test negative, according to a provocative study that linked thousands of blood bank records to Israel's national cancer registry.

Absolute cancer risk was small in the study: Of people with positive direct antiglobulin tests (DATs), 2.9% developed cancer, compared with 1.2% of DAT-negative donors, Dr. Ora Paltiel reported in a poster at the annual meeting of the American Society of Hematology.

Relative cancer risk was high, however, with hazard ratios of 2.46 overall, 14.20 for hematopoietic cancers, and 8.02 for lymphomas. Even when the investigators excluded cases diagnosed within 12 months of blood donation, people with positive DAT tests had an eightfold higher risk of developing a hematopoietic cancer at an average follow-up of 66 months.

“In a small minority of people, a positive DAT is actually a marker—not a risk factor, a marker—that they have some cancer growing,” said Dr. Paltiel, a hematologist and epidemiologist at the Hadassah University Medical Center, Jerusalem.

“Practically, you would not want to bring a panic because of this, but there are implications to a positive DAT,” she said, urging additional studies to confirm the finding and determine whether DAT testing could help detect early cancers in healthy people.

The DAT test (also known as a direct Coombs' test) has been used since the 1950s to see whether the donor has immunoglobulin antibodies attached to red blood cells, according to Dr. Paltiel. It is not universally required of blood donors, but a positive finding can suggest an immune reaction to a disease process.

The investigators identified 586 blood donors who had positive DAT screens during the years 1993–2003, and matched them by gender, age, and year of blood donation to 2,344 DAT-negative donors. Using unique identification numbers, the study was able to determine cancer incidence through July 30, 2006, in both cohorts. Men made up 63% of the population. The DAT-positive donors were slightly older (34.5 years vs. 32 years on average).

All told, 17 DAT-positive donors and 27 DAT-negative donors developed cancer by mid-2006. Dr. Paltiel said that DAT-positive patients tended to be diagnosed with cancer earlier than those who were DAT negative, perhaps because they had a physical exam after receiving letters notifying them of the DAT results. Three DAT-positive donors were diagnosed with hematopoietic cancers (Hodgkin's lymphoma, non-Hodgkin's lymphoma, and multiple myeloma) during the first year.

The investigators did a subset analysis excluding early diagnoses in people who may have had undiagnosed cancers at the time of blood donation. Looking just at DAT-positive donors diagnosed with cancers after 12 months, the most common malignancies (with two in each category) were lymphoma, multiple myeloma, and thyroid, prostate, and gastrointestinal tumors.

Comparisons of observed cases of cancer in blood donors with expected cases in the general population also found twice the incidence of cancer in DAT-positive donors, but no elevation of cancer rates in those who had tested DAT negative. Incidence of hematologic malignancies was 11-fold higher in the DAT-positive donors, according to the poster. This reflected somewhat increased rates of lymphomas and Hodgkin's lymphoma and a more than 40-fold hike in incidence of multiple myeloma, compared with expected rates.

The increase in a condition as rare as multiple myeloma cannot simply be attributed to more people being screened after a positive DAT test, Dr. Paltiel said. “Some of it has to do with health behavior, but you can't blame myeloma on health behavior.” If a positive DAT leads to earlier diagnosis, she added, the person could benefit from recent advances in treatment of multiple myeloma.

'A positive DAT is actually a marker—not a risk factor, a marker—that they have some cancer growing.' DR. PALTIEL