STOCKHOLM, Sweden—Persistent leucopenia and anemia may predispose patients with systemic lupus erythematosus (SLE) to myeloid leukemia and should be vigorously evaluated, according to a new paper in Rheumatology.¹ Immunosupressive therapy was not culpable, the study showed.

“SLE patients with prolonged cytopenias and in particular leucopenia should therefore, irrespective of treatment, be subject to a bone marrow investigation,” conclude the researchers who were led by Björn Löftsrum, MD, a rheumatologist at Karolinska University Hospital in Stockholm, Sweden.

Leucopenias are red flag for SLE leukemia risk

Dr. Löftsrum and colleagues compared 8 SLE patients with acute or chronic myeloid leukemia to 18 SLE controls using data from the Swedish Hospital Discharge Register for SLE discharge diagnoses from 1964 to 1995, and the national cancer register.

They concluded that risk factors for myeloid leukemia included preceding leucopenia. Other SLE manifestations were not risk factors for leukemia.

Moreover, two lupus cases had a preceding bone marrow confirming myelodysplastic syndrome (MDS). Only two cases were significantly treated with cyclophosphamide or azathioprine (AZA).

The researchers conducted a Medline search that showed only 15 previously published cases of coincident SLE and myeloid leukemia. Of these, there was preceding MDS in 5 cases, and only 8 had been treated with cytotoxic drugs.

Low-dose CT not the cause of myeloid malignancies in SLE patients

“Low-dose chemotherapy was not a major cause of myeloid malignancy in our population-based cohort of SLE patients nor in the reported cases from literature,” the researchers conclude. That said, “leucopenia was a risk factor for myeloid leukemia development, and MDS was frequently seen.”

Translating research into practice: BM biopsy for SLE with persistent leucopenia

“This study was not a study of the risk of leukemia in SLE patients compared to healthy people,” stresses Joan T. Merrill, MD, head of the clinical pharmacology research program at the Oklahoma Medical Research Foundation in Oklahoma City, Oklahoma, and medical director of the Lupus Foundation of America. “There is no evidence anywhere in the literature that leukemia is more likely in lupus than in the general population.”

This study compared the differences between 8 people with SLE who developed myeloid leukemia and some people with SLE who did not develop leukemia, she said. “They found that low white blood cells and a prior diagnosis of myelodysplastic syndrome were more likely to be found in those with leukemia than those without [and] this is likely to be true whether or not people have SLE since low white blood cell counts are found as people develop leukemia and there is already an association with myelodysplastic syndrome and leukemia,” she says.

“Lupus patients with prolonged low white blood cell counts should get a bone marrow test,” she said. “This seems sensible. It would be possible to miss early leukemia (especially when it is quite rare) in patients who have a chronic disease like lupus where we usually would not think of attributing the low white blood cells to leukemia given that this finding in lupus is much more commonly due to lupus itself or some of the treatments that we use,” she said.

Robert G. Lahita, MD, PhD, professor of medicine at Mount Sinai Medical School, in New York, and chairman of medicine at the Jersey City Medical Center, in New Jersey, adds that “one of the few ‘cheap’ signs of lupus activity is leucopenia,” he says. “This has been known for many years and would preclude doing a search for leukemia in every patient with a low white count or anemia. I have never seen a myeloid leukemia in any of the many patients that we see.”

Reference

1. Löftsrum, B, Backlin Cm Sundström C, et al. Myleloid leukaemia ins systemic lupus erythematosus- a nested case-control study based ion Swedish registers. Rheumatology. 2009; [epub ahead of print July 16, 2009].