Long-term immunosuppression and multiple transplants predispose systemic lupus erythematosus patients with cytopenias to hematologic malignancies

Abstract

Cytopenias in systemic lupus erythematosus (SLE) require clinical and laboratory workup and bone marrow (BM) examination to determine the cause and for appropriate patient management. Common causes include an increase in SLE activity, immunemediated hemolysis, iron deficiency, antiphospholipid antibody syndrome, infection, or the effect of medications. We retrospectively evaluated the clinical and laboratory findings of patients with SLE and cytopenias who had undergone BM studies to determine the indicators of malignancy.We retrospectively reviewed medical records of patients with SLE who presented with cytopenias for their disease course, medications, laboratory parameters and documented the spectrum of morphological changes in BM including CD34 expression.Twenty patients with SLE had undergone BM biopsy for evaluation of cytopenias. 14/20 (70%) of the patients had reactive BM, and the rest had hematologic malignancies involving the BM. Of these 14 patients, 8 had hypocellular marrow with loss of precursor cells (low CD34), 4 had left shift in myeloid lineage, 3 had serous atrophy, and 1had multilineage dysplasia. The 6 patients with hematologic malignancies included 2 with diffuse large B cell lymphoma, and one each of natural killer/T cell lymphoma, post-transplant lymphoproliferative disorder, Hodgkin lymphoma, and myelodysplastic syndrome evolving to acute myelogenous leukemia. The presence of autoantibodies, SLE activity, and lupus nephritis were comparable in patients with and without neoplasia. However, the duration of the use of multiple immunosuppressants, years since renal transplant (22 vs 10), multiple transplants, and the presence of other autoimmune diseases were greater in those with neoplasia. Two of the 14 patients with non-neoplastic BM and 1 with the neoplastic BM had nonhematological malignancy.Clinical and laboratory findings, the number of transplants, and the use of immunosuppressive agents can guide physicians to identify patients with a higher risk of developing hematologic malignancy. BM findings of cytopenia in SLE are often due to increased disease activity causing global cell death and dysmaturation. SLE patients presenting with cytopenias, with a history of long-term exposure to immunosuppressive drugs, should be regularly screened for hematologic and nonhematologic malignancies.Abbreviations: anti-dsDNA = anti-double stranded DNA, aPL = anti-phospholipid antibodies, AZA = azathioprine, BM = bone marrow, Hgb = hemoglobin, MDS = myelodysplastic syndrome, MTX = methotrexate, NHL = non-Hodgkin lymphoma, SLE = systemic lupus erythematosus.

Immune Phenomena in Myeloid Neoplasms: An “Egg or Chicken” Question

“…On the other hand, there is evidence that patients with prior systemic autoimmune rheumatic diseases have an increased risk for the development of hematological malignancies, particularly lymphomas and MDS. This has been reported for RA, SS, SLE, ITP, myasthenia gravis, and giant cell arteritis, suggesting that the immune dysregulation underlying the autoimmune disease may be involved in the generation of a "tumor permissive" soil, although the contribution of treatment with immunosuppressive/cytotoxic drugs cannot be excluded (15)(16)(17).…”