Mazzaro C, Franzin F, Tulissi P, Pussini E, Crovatto M, Carniello G S, Efremov D G, Burrone O, Santini G, Pozzato G
First Department of Medicine, Pordenone General Hospital, Italy.
Cancer. 1996 Jun 15;77(12):2604-13. doi: 10.1002/(SICI)1097-0142(19960615)77:12<2604::AID-CNCR26>3.0.CO;2-V.
Several authors have reported on the effectiveness of alpha-interferon (IFN-alpha) in the treatment of patients with mixed cryoglobulinemia. This prompted the authors to investigate the long term effects of this drug on clinical, hematologic, and virologic parameters in a group of 20 patients (13 women and 7 men) affected by mixed cryoglobulinemia.
In all patients, bone marrow biopsy, phenotyping of marrow cells, and polymerase chain reaction (PCR) immunoglobulin gene rearrangement in peripheral blood lymphocytes were performed before therapy and at the end of the follow-up. A liver biopsy was obtained in patients with biochemical signs of chronic liver disease. The presence of hepatitis C virus (HCV) RNA in serum was assessed by detection of anti-HCV antibodies, and by PCR amplification of the 5' untranslated region of HCV. The HCV genotype was also determined by PCR amplification of the core region of the virus with type-specific primers. The treatment schedule followed by all patients was 3 million units of recombinant IFN-alpha 2b 3 times weekly for 1 year.
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 were present in 19 (95%) subjects, and HCV-RNA was detectable in all patients. In addition, all patients affected by Type II mixed cryoglobulinemia showed a monoclonal B-cell expansion in peripheral blood mononuclear cells (PBMC). With therapy, 5 patients (25%) achieved a complete response and 11 patients (55%) a partial response, whereas minor responses were observed in the remaining 4 patients (20%). One of the complete responders and all patients showing partial responses relapsed a few months after therapy withdrawal. At the end of the follow-up, four patients had obtained a complete remission. Bone marrow examination showed that B-lymphocytic monoclonal infiltrate disappeared in three patients. Moreover, these three patients had become negative for B-cell expansion in PBMC. Lack of response, or relapse, was associated with the presence of Type II HCV.
HCV may be the cause of mixed cryoglobulinemia. The disease is associated with a high prevalence of bone marrow B-cell lymphomas. IFN-alpha appears to be an effective agent for the treatment of mixed cryoglobulinemia. It also seems able to determine regression of the lymphoproliferative disorder. The HCV genotype appears to be the most important predictive factor for the response to antiviral therapy.
多位作者报道了α-干扰素（IFN-α）治疗混合性冷球蛋白血症患者的有效性。这促使作者研究该药物对一组20例（13名女性和7名男性）混合性冷球蛋白血症患者临床、血液学和病毒学参数的长期影响。
对所有患者在治疗前及随访结束时进行骨髓活检、骨髓细胞表型分析以及外周血淋巴细胞聚合酶链反应（PCR）免疫球蛋白基因重排检测。对有慢性肝病生化指标的患者进行肝活检。通过检测抗丙型肝炎病毒（HCV）抗体以及对HCV 5'非翻译区进行PCR扩增来评估血清中HCV RNA的存在情况。还通过用型特异性引物对病毒核心区进行PCR扩增来确定HCV基因型。所有患者的治疗方案为每周3次，每次300万单位重组IFN-α 2b，共治疗1年。
6例患者治疗前骨髓组织学显示浆细胞样淋巴细胞大量（超过50%）单形性浸润，提示存在低度非霍奇金淋巴瘤。19例（95%）受试者存在抗HCV抗体，所有患者均可检测到HCV-RNA。此外，所有II型混合性冷球蛋白血症患者外周血单个核细胞（PBMC）中均出现单克隆B细胞扩增。治疗后，5例患者（25%）达到完全缓解，11例患者（55%）部分缓解，其余4例患者（20%）出现轻微反应。1例完全缓解者及所有部分缓解患者在停药数月后复发。随访结束时，4例患者获得完全缓解。骨髓检查显示3例患者B淋巴细胞单克隆浸润消失。此外，这3例患者PBMC中B细胞扩增转阴。无反应或复发与II型HCV的存在有关。
HCV可能是混合性冷球蛋白血症的病因。该疾病与骨髓B细胞淋巴瘤的高患病率相关。IFN-α似乎是治疗混合性冷球蛋白血症的有效药物。它似乎还能使淋巴增殖性疾病消退。HCV基因型似乎是抗病毒治疗反应的最重要预测因素。
