现行的真性红细胞增多症的治疗推荐呼吁保持红细胞比容（hematocrit）少于45%，但这一治疗策略并未得到随机化临床试验的验证。意大利Consorzio Mario Negri Sud研究所的Marchioli博士等人对此进行了深入研究，他们发现，对于真性红细胞增多症，与红细胞比容处于45%—50%的患者相比，达到红细胞比容少于45%目标的患者心血管死亡和主要静脉血栓显著性降低。论文发表于国际权威杂志NEJM 2013年1月3日在线版。
研究人员对365例曾接受静脉切开术、羟脲、或二者联合治疗的JAK2阳性的真性红细胞增多症患者随机分组，分别给予强强化治疗方案（目标红细胞比容，<45%）（低红细胞比容组）或弱强化治疗方案（目标红细胞比容，45—50%）。试验主要复合终点为至心血管原因死亡或主要血栓形成事件的时间。次要终点为心血管事件、心血管事件住院治疗、癌症发生率、进展至骨髓纤维化症、脊髓发育不良或白血病转化、以及出血事件。研究人员还进行了意向治疗分析。
结果显示，在经过31个月的中位随访期后，研究人员报道低红细胞比容组182例患者中有5例(2.7%)，高红细胞比容组183例患者中有18例(9.8%)达到主要终点（高红细胞比容组风险比3.91; 95% 置信区间[CI], 1.45 至10.53; P=0.007）。研究人员统计发现，低红细胞比容组有4.4%的患者达到主要终点及浅静脉血栓形成，与之相比高红细胞比容则为10.9%（风险比，2.69; 95% CI, 1.19 至6.12; P=0.02）。研究观察到低红细胞比容组进展至骨髓纤维化、脊髓发育不良或白血病转化以及出血的患者分别有6、2、2例，与之相比，高红细胞比容组则分别有2、1、5例。不良事件发生率未见显著性组间差异。
研究人员由此得出结论，对于真性红细胞增多症，与红细胞比容处于45%—50%的患者相比，达到红细胞比容少于45%目标的患者心血管死亡和主要静脉血栓显著性降低。
DOI: 10.1056/NEJMoa1208500
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Cardiovascular Events and Intensity of Treatment in Polycythemia Vera
Roberto Marchioli, M.D., Guido Finazzi, M.D., Giorgina Specchia, M.D., Rossella Cacciola, M.D., Ph.D., Riccardo Cavazzina, Sc.D., Daniela Cilloni, M.D., Ph.D., Valerio De Stefano, M.D., Elena Elli, M.D., Alessandra Iurlo, M.D., Ph.D., Roberto Latagliata, M.D., Francesca Lunghi, M.D., Monia Lunghi, M.D., Rosa Maria Marfisi, M.S., Pellegrino Musto, M.D., Arianna Masciulli, M.D., Ph.D., Caterina Musolino, M.D., Ph.D., Nicola Cascavilla, M.D., Giovanni Quarta, M.D., Maria Luigia Randi, M.D., Davide Rapezzi, M.D., Marco Ruggeri, M.D., Elisa Rumi, M.D., Anna Rita Scortechini, M.D., Simone Santini, M.D., Marco Scarano, Sc.D., Sergio Siragusa, M.D., Antonio Spadea, M.D., Ph.D., Alessia Tieghi, M.D., Emanuele Angelucci, M.D., Giuseppe Visani, M.D., Alessandro Maria Vannucchi, M.D., and Tiziano Barbui, M.D. for the CYTO-PV Collaborative Group
BACKGROUND
Current treatment recommendations for patients with polycythemia vera call for maintaining a hematocrit of less than 45%, but this therapeutic strategy has not been tested in a randomized clinical trial.
METHODS
We randomly assigned 365 adults with JAK2-positive polycythemia vera who were being treated with phlebotomy, hydroxyurea, or both to receive either more intensive treatment (target hematocrit, <45%) (low-hematocrit group) or less intensive treatment (target hematocrit, 45 to 50%) (high-hematocrit group). The primary composite end point was the time until death from cardiovascular causes or major thrombotic events. The secondary end points were cardiovascular events, cardiovascular hospitalizations, incidence of cancer, progression to myelofibrosis, myelodysplasia or leukemic transformation, and hemorrhage. An intention-to-treat analysis was performed.
RESULTS
After a median follow-up of 31 months, the primary end point was recorded in 5 of 182 patients in the low-hematocrit group (2.7%) and 18 of 183 patients in the high-hematocrit group (9.8%) (hazard ratio in the high-hematocrit group, 3.91; 95% confidence interval [CI], 1.45 to 10.53; P=0.007). The primary end point plus superficial-vein thrombosis occurred in 4.4% of patients in the low-hematocrit group, as compared with 10.9% in the high-hematocrit group (hazard ratio, 2.69; 95% CI, 1.19 to 6.12; P=0.02). Progression to myelofibrosis, myelodysplasia or leukemic transformation, and bleeding were observed in 6, 2, and 2 patients, respectively, in the low-hematocrit group, as compared with 2, 1, and 5 patients, respectively, in the high-hematocrit group. There was no significant between-group difference in the rate of adverse events.
CONCLUSIONS
In patients with polycythemia vera, those with a hematocrit target of less than 45% had a significantly lower rate of cardiovascular death and major thrombosis than did those with a hematocrit target of 45 to 50%。
