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Future Development of Lymphoproliferative Disorders in Patients with Autoimmune Hemolytic Anemia

Divisions of Hematology/Oncology [S.S.] and Biostatistics [J.Y.W.], University of Tennessee Health Science Center, Memphis, Tennessee 38103, and Department of Pathology and Laboratory Medicine, East Carolina University, Greenville, North Carolina 27858-4353 [L.R.H.]

The association between autoimmune hemolytic anemia (AIHA) and subsequent appearance of lymphoproliferative disorders (LPDs) has not been properly addressed in large-scale studies. We evaluated 107 patients with idiopathic (67 patients) or underlying (40 patients) immune disorders diagnosed with AIHA between 1992 and 1999. The following variables were examined in univariate and multivariate analysis: age; sex; type of AIHA (warm- or cold-active antibodies); presence of underlying immune disorders; and serum monoclonal protein. Of the 107 patients, 19 (18%) developed malignant LPDs. The median time to develop malignancy was 26.5 months (range, 9–76 months). At multivariate analysis, advanced age (P = 0.005), underlying autoimmune diseases (P = 0.002), and the presence of serum gammopathy (P = 0.045) were risk factors for future development of LPDs in these patients. Also, serum monoclonal IgM protein was a significant predictor (P = 0.0001) for the appearance of LPDs in patients with AIHA. The present study provides evidence that AIHA in some patients should be considered as a precursor of malignant LPDs. Knowledge of certain characteristics may help identify patients at risk for this transformation; periodic clinical and laboratory assessment of these patients is warranted.

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