Talpaz M, Kurzrock R, Kantarjian H, O'Brien S, Gutterman J U
Department of Clinical Immunology and Biological Therapy, University of Texas, M.D. Anderson Cancer Center, Houston 77030.
Am J Med. 1989 May;86(5):554-8. doi: 10.1016/0002-9343(89)90384-7.
The clinical course of patients with myeloproliferative disorders and excessive thrombocytosis may be complicated by serious hemorrhagic or thrombotic events. We have previously reported that interferon-alpha can control severe refractory thrombocytosis in patients with advanced chronic myelogenous leukemia. Therefore, we treated a group of thrombocythemic patients with Ph-negative myeloproliferative disorders, including polycythemia vera and essential thrombocythemia, with recombinant interferon-alpha (rIFN-alpha 2a).
Eight patients with profound elevations in platelet counts received a median induction dose of 5.4 X 10(6) U/day (range, 5.0 to 10.0 X 10(6) U/day) of rIFN-alpha 2a administered intramuscularly or subcutaneously.
We observed a significant decline in platelet counts from a median baseline value of 1,929 X 10(9)/L (range, 960 to 2,960 X 10(9)/L) to a median posttreatment value of 431 X 10(9)/L (range, 71 to 1,150 X 10(9)/L) (p less than 0.01). Concomitantly, white blood cell counts declined from a median baseline value of 20.8 X 10(9)/L (range, 10.5 to 40.8 X 10(9)/L) to a median posttreatment value of 6.1 X 10(9)/L (range, 2.9 to 29.0 X 10(9)/L) (p less than 0.02). Correction of thrombocytosis was rapid, with a median of only eight days from the start of therapy to the achievement of a platelet count less than 1,000 X 10(9)/L. Six of eight patients have shown an ongoing response with a median follow-up period of 11 months (range, one to 30 months). There have been no bleeding or thrombotic events during the study. Side effects of rIFN-alpha 2a therapy consisted of fever and flu-like symptoms, with tachyphylaxis developing after one to two weeks of therapy.
Our observations suggest that alpha interferon may be a promising therapeutic agent for myeloproliferative disorders characterized by thrombocytosis.
骨髓增殖性疾病和血小板增多症患者的临床病程可能会因严重的出血或血栓形成事件而复杂化。我们之前曾报道,α干扰素可控制晚期慢性粒细胞白血病患者的严重难治性血小板增多症。因此,我们用重组α干扰素(rIFN-α2a)治疗了一组血小板增多的Ph阴性骨髓增殖性疾病患者,包括真性红细胞增多症和原发性血小板增多症。
8例血小板计数显著升高的患者接受了中位诱导剂量为5.4×10⁶U/天(范围为5.0至10.0×10⁶U/天)的rIFN-α2a,通过肌肉注射或皮下注射给药。
我们观察到血小板计数从基线中位值1929×10⁹/L(范围为960至2960×10⁹/L)显著下降至治疗后中位值431×10⁹/L(范围为71至1150×10⁹/L)(p<0.01)。同时,白细胞计数从基线中位值20.8×10⁹/L(范围为10.5至40.8×10⁹/L)下降至治疗后中位值6.1×10⁹/L(范围为2.9至29.0×10⁹/L)(p<0.02)。血小板增多症的纠正迅速,从治疗开始到血小板计数低于1000×10⁹/L的中位时间仅为8天。8例患者中有6例在中位随访期11个月(范围为1至30个月)时显示持续缓解。研究期间未发生出血或血栓形成事件。rIFN-α2a治疗的副作用包括发热和流感样症状,治疗1至2周后出现快速耐受。
我们的观察结果表明,α干扰素可能是治疗以血小板增多为特征的骨髓增殖性疾病的一种有前景的治疗药物。