Ziegler-Heitbrock H W, Schlag R, Flieger D, Thiel E
Institute for Immunology, University of Munich, FRG.
Blood. 1989 May 1;73(6):1426-30.
Since interferon (IFN-alpha) treatment has proven effective in hairy cell leukemia, its evaluation in chronic lymphocytic leukemia (CLL), a cytologically related disease, appeared reasonable. In our study, we have focused on previously untreated, early stage patients who are less than 60 years of age. All patients had less than 50,000 lymphocytes/microL and immunologic analysis revealed a CD20+, IgM+, IgD- phenotype for leukemic B cells in eight of nine patients. Recombinant interferon alpha 2b (IFN-alpha 2) at 5 x 10(6) U was given subcutaneously three times per week for 8 to 16 months. Consistent with earlier reports, side effects were minor with this low-dose protocol. All patients responded with a decrease of WBC count and lymphocyte count; in one patient, splenomegaly resolved such that he moved from Rai stage II to Rai stage I. On the average CD20+ B cells decreased from 14,312 to 3,995 cells/microL, indicating that no complete eradication of the leukemic cells was possible. A partial response, based on a greater than 50% reduction of CD20+ B cells was obtained in five of seven patients analyzed. The increased numbers of CD2+ T lymphocytes decreased in response to interferon treatment in six of seven patients. Furthermore, in a portion of the patients class II antigen expression was enhanced on LeuM3+ monocytes suggesting an in vivo activation of the monocytes by IFN-alpha 2. Immunoglobulin levels were substantially improved in that serum IgG increased by more than 3 g/L in three of seven patients. In one patient, lymphocyte counts increased in spite of continued therapy, whereas all others exhibited no increase of lymphocyte numbers while on therapy. Our study clearly demonstrates effects of IFN-alpha 2 treatment on both the leukemic cells and on the nonleukemic components of the immune system in peripheral blood. Whether IFN-alpha treatment will result in long-term beneficial effects in early stage CLL needs to be evaluated in a larger study.
由于干扰素（IFN-α）治疗已被证明对毛细胞白血病有效，因此在慢性淋巴细胞白血病（CLL）（一种细胞学相关疾病）中对其进行评估似乎是合理的。在我们的研究中，我们重点关注年龄小于60岁、未经治疗的早期患者。所有患者的淋巴细胞计数均低于50,000/微升，免疫分析显示9例患者中有8例白血病B细胞的表型为CD20 +、IgM +、IgD -。重组干扰素α2b（IFN-α2）以5×10⁶U的剂量每周皮下注射3次，持续8至16个月。与早期报告一致，该低剂量方案的副作用较小。所有患者的白细胞计数和淋巴细胞计数均下降；1例患者的脾肿大消失，其分期从Rai II期转变为Rai I期。平均而言，CD20 + B细胞从14,312个/微升降至3,995个/微升，这表明不可能完全清除白血病细胞。在7例接受分析的患者中，有5例获得了部分缓解，即CD20 + B细胞减少超过50%。7例患者中有6例的CD2 + T淋巴细胞数量增加在干扰素治疗后减少。此外，在部分患者中，LeuM3 +单核细胞上的II类抗原表达增强，提示IFN-α2在体内激活了单核细胞。7例患者中有3例的血清IgG增加超过3 g/L，免疫球蛋白水平得到显著改善。1例患者在持续治疗期间淋巴细胞计数增加，而其他所有患者在治疗期间淋巴细胞数量均未增加。我们的研究清楚地证明了IFN-α2治疗对外周血中白血病细胞和免疫系统非白血病成分的影响。IFN-α治疗是否会对早期CLL产生长期有益影响，需要在更大规模的研究中进行评估。
