Sacchi S
Dipartimento di Scienze Mediche, Oncologiche e Radiologiche, Modena, Italy.
Leuk Lymphoma. 1995 Sep;19(1-2):13-20. doi: 10.3109/10428199509059658.
Treatment of essential thrombocythaemia (ET), polycythaemia vera (PV), and myelofibrosis with myeloid metaplasia (MMM) patients is frequently a difficult issue. To date, there is no generally accepted treatment for these diseases which can reduce the risk of thromboembolism and/or haemorrhagic events, avoid any increase in the frequency of secondary myelofibrosis and terminal blast transformation and decrease the reticulin content in the bone marrow of MMM patients. The most frequently used myelosuppressive agent is hydroxyurea (HU), but widespread application has failed to demonstrate that is not leukaemogenic. In patients with MMM, conflicting results have been obtained following alpha-IFN treatment. Haematological responses have been seen in 50% of the patients. Usually the patients showing good responses had a hyperproliferative type of disease. In only one case was a reduction of reticulin content of the bone marrow observed. Thus, these findings do not indicate alpha-IFN as a first-line therapy. On the other hand, the results of several reports in ET and PV patients have shown a reduction in the abnormal proliferation of megakaryocytes and erythroid elements, following alpha-IFN treatment. A reduction in spleen size has also frequently been seen. Together with the improvement of haematological parameters, clinical symptoms have also responded positively. Long term control of these diseases can be obtained with a well-tolerated low dose of alpha-IFN. However, PV and ET are not usually characterized by cytogenetic abnormalities, making it very difficult to demonstrate the disappearance of clonal haemopoiesis following alpha-IFN therapy, even if this does occasionally occur, as evident from the two cytogenetic convertions described in the literature. As compared to myelosuppressive drugs or phlebotomy, alpha-IFN thus represents an attractive new treatment, able to exert a fundamental influence on these diseases, presumably without any untoward leukaemogenic or gonadotoxic activity.
真性红细胞增多症（ET）、原发性血小板增多症（PV）以及伴有骨髓化生的骨髓纤维化（MMM）患者的治疗常常是个难题。迄今为止，对于这些疾病尚无普遍接受的治疗方法能够降低血栓栓塞和/或出血事件的风险、避免继发性骨髓纤维化和终末期原始细胞转化频率的增加以及减少MMM患者骨髓中的网硬蛋白含量。最常用的骨髓抑制药物是羟基脲（HU），但广泛应用未能证明其无致白血病作用。对于MMM患者，α干扰素治疗后结果相互矛盾。50%的患者出现血液学反应。通常显示良好反应的患者患有增殖活跃型疾病。仅在1例中观察到骨髓网硬蛋白含量降低。因此，这些结果并不表明α干扰素可作为一线治疗药物。另一方面，多篇关于ET和PV患者的报道结果显示，α干扰素治疗后巨核细胞和红系细胞的异常增殖减少。脾脏大小也经常减小。随着血液学参数的改善，临床症状也有积极反应。低剂量的α干扰素耐受性良好，可实现对这些疾病的长期控制。然而，PV和ET通常无细胞遗传学异常，即使偶尔出现文献中描述的两次细胞遗传学转化那样的情况，也很难证明α干扰素治疗后克隆性造血消失。与骨髓抑制药物或放血疗法相比，α干扰素因此代表了一种有吸引力的新治疗方法，可能对这些疾病产生根本性影响，且可能无不良的致白血病或性腺毒性活性。
