SNOWMASS, COLO. — A wide range of rheumatic diseases is associated with increased risk for myeloid malignancies, according to an analysis of the National Cancer Institute's Surveillance, Epidemiology and End Results database.

Epidemiologic studies such as this SEER analysis can't address causation. But it's clear that much of the increased risk of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) in patients with rheumatoid arthritis, systemic lupus erythematosus (SLE), and other rheumatic diseases is a consequence of the medications used in treating the autoimmune disease, Dr. Maria R. Baer said at a symposium sponsored by the American College of Rheumatology.

Shared genetic predisposition and extension of the rheumatic disease into the bone marrow are other possible explanations.

There is a well-established association between rheumatic conditions and an increased risk of lymphoma. The risk of myeloid malignancies in rheumatology patients has, until recently, undergone far less scrutiny, noted Dr. Baer, a hematologist and oncologist at the cancer center of the University of Maryland in Baltimore.

The retrospective, case-control SEER study, conducted by investigators at Queen's University of Belfast (Northern Ireland), incorporated 13,486 U.S. patients with myeloid malignancies and 160,086 controls.

Multiple logistic regression analyses, adjusted for potential confounders, showed that rheumatic diseases were associated with an overall 1.29-fold increased risk of AML. The AML risk varied by the specific rheumatologic disease. It was greatest in systemic vasculitis patients, who were at 6.23-fold greater risk than were controls who were free of rheumatic diseases.

On the other hand, systemic vasculitis was the only rheumatic disease included in the study that was not associated with an elevated risk of MDS. (See box.)

The autoimmune diseases weren't associated with overall increased risks of chronic myeloid leukemia or chronic myeloproliferative disorders (Br. J. Cancer 2009;100:822–8).

Another informative, large, retrospective cohort study was conducted by investigators at the California Cancer Registry. They found that in 30,478 patients with SLE who were followed for nearly 158,000 person-years, the risk of myeloid leukemia was increased 2.96-fold. The SLE patients also had a 2.7-fold increased risk of liver cancer, a 3.27-fold increased of vaginal/vulvar cancer, and elevated risks of lung, thyroid, and renal cancers (Cancer Causes Control 2008;19:887–94).

The same team of investigators subsequently studied 84,475 rheumatoid arthritis patients over an observation period stretching in excess of 405,000 person-years. The patients proved to have significantly increased risks of hematopoietic, lung, liver, and esophageal cancers. They also had lower-than-average rates of several screenable cancers, as did the SLE patients in the earlier study (Cancer Causes Control 2009;20:1001–10).

Cytotoxic therapy–related MDS and AML (abbreviated by hematologists as t-MDS and t-AML) have a readily identifiable pathological pattern. It is characterized by morphological dysplasia of the bone marrow and clonal cytogenetic abnormalities, most often loss of part or all of chromosome 5 or 7 or both. Although t-MDS often evolves into t-AML, t-AML isn't always preceded by t-MDS. The distinction between the two, as arbitrarily defined by the World Health Organization, is that t-AML features at least 20% myeloblasts, Dr. Baer continued.

Methotrexate use doesn't appear to be linked to the increased risk of t-MDS or t-AML, although it is associated with an increased risk of lymphoma.

In contrast, cyclophosphamide is a major culprit in the t-MDS and t-AML that are encountered in rheumatology patients. In what Dr. Baer termed “a classic” study, Danish investigators showed that in a cohort of 293 patients with Wegener's granulomatosis who were followed for 2,121 person-years, the risk of AML was increased 19.6-fold overall, compared with that of the general population. The risk was not elevated above that in controls for Wegener's patients who had received a cumulative 36 g or less of cyclophosphamide. However, patients who had received more than 36 g (equivalent to 100 mg/day for more than a year) had a 59-fold increased risk of AML (J. Rheumatol. 2008;35:100–5).

Both t-MDS and t-AML are “bad entities,” she emphasized. The first question to ask is whether an affected patient is a candidate for aggressive therapy with allogeneic hematopoietic stem cell transplantation—the clear treatment of choice—and if so, whether a donor is available.

“The outcome is really dismal, transplant or no transplant. You want to modulate your rheumatologic therapy to avoid this complication because it's quite devastating when it does occur,” Dr. Baer said.

She offered as one representative series a 306-patient University of Chicago cohort. Their median survival after diagnosis of t-MDS or t-AML was 8 months, with a 5-year survival of less than 10% (Blood 2003;102:43–52).

Disclosures: Dr. Baer reported no relevant financial relationships.

70194_fx1.sml

Source Elsevier Global Medical News

Rheum Disorders May Up Risk for Myeloid Malignancy