REGRESSION OF MONOCLONAL B-CELL EXPANSION IN PATIENTS AFFECTED BY MIXED CRYOGLOBULINEMIA RESPONSIVE TO ALPHA-INTERFERON THERAPY

BACKGROUND. Several authors have reported on the effectiveness of alph a-interferon (IFN-alpha) in the treatment of patients with mixed cryog lobulinemia. This prompted the authors to investigate the long term ef fects of this drug on clinical, hematologic, and virologic parameters in a group of 20 patients (13 women and 7 men) affected by mixed cryog lobulinemia. METHODS. In all patients, bone marrow biopsy, phenotyping of marrow cells, and polymerase chain reaction (PCR) immunoglobulin g ene rearrangement in peripheral blood lymphocytes were performed befor e therapy and at the end of the follow-up. A liver biopsy was obtained in patients with biochemical signs of chronic liver disease. The pres ence of hepatitis C virus (HCV) RNA in serum was assessed by detection of anti-HCV antibodies, and by PCR amplification of the 5' untranslat ed region of HCV. The HCV genotype was also determined by PCR amplific ation of th core region of the virus with type-specific primers. The t reatment schedule followed by all patients was 3 million units of reco mbinant IFN-alpha 2b 3 times weekly for 1 year. RESULTS. In 6 patients , the marrow histology before therapy showed a massive (more than 50%) monomorphous infiltration by plasmacytoid lymphocytes, indicating the presence of low grade non-Hodgkin's lymphoma. Anti-HCV antibodies wer e present in 19 (95%) subjects, and HCV-RNA was detectable in all pati ents. In addition, all patients affected by Type II mixed cryoglobulin emia showed a monoclonal B-cell expansion in peripheral blood mononucl ear cells (PBMC). With therapy, 5 patients (25%) achieved a complete r esponse and 11 patients (55%) a partial response, whereas minor respon ses were observed in the remaining 4 patients (20%). One of the comple te responders and all patients showing partial responses relapsed a fe w months after therapy withdrawal. At the end of the follow-up, four p atients had obtained a complete remission. Bone marrow examination sho wed that B-lymphocytic monoclonal infiltrate disappeared in three pati ents. Moreover, these three patients had become negative for B-cell ex pansion in PBMC. Lack of response, or relapse, was associated with the presence of Type II HCV. CONCLUSIONS. HCV may be the cause of mixed c ryoglobulinemia. The disease is associated with a high prevalence of b one marrow B-cell lymphomas. IFN-alpha appears to be an effective agen t for the treatment of mixed cryoglobulinemia. It also seems able to d etermine regression of the lymphoproliferative disorder. The HCV genot ype appears to be the most important predictive factor for the respons e to antiviral therapy. (C) 1996 American Cancer Society.