Hellström-Lindberg E, Ahlgren T, Beguin Y, Carlsson M, Carneskog J, Dahl I M, Dybedal I, Grimfors G, Kanter-Lewensohn L, Linder O, Luthman M, Löfvenberg E, Nilsson-Ehle H, Samuelsson J, Tangen J M, Winqvist I, Oberg G, Osterborg A, Ost A
Department of Hematology, Huddinge University Hospital, Huddinge, Sweden.
Blood. 1998 Jul 1;92(1):68-75.
Treatment with erythropoietin (epo) may improve the anemia of myelodysplastic syndromes (MDS) in approximately 20% of patients. Previous studies have suggested that treatment with the combination of granulocyte colony-stimulating factor (G-CSF) and epo may increase this response rate. In the present phase II study, patients with MDS and anemia were randomized to treatment with G-CSF + epo according to one of two alternatives; arm A starting with G-CSF for 4 weeks followed by the combination for 12 weeks, and arm B starting with epo for 8 weeks followed by the combination for 10 weeks. Fifty evaluable patients (10 refractory anemia [RA], 13 refractory anemia with ring sideroblasts [RARS], and 27 refractory anemia with excess blasts [RAEB]) were included in the study, three were evaluable only for epo as monotherapy and 47 for the combined treatment. The overall response rate to G-CSF + epo was 38%, which is identical to that in our previous study. The response rates for patients with RA, RARS, and RAEB were 20%, 46%, and 37%, respectively. Response rates were identical in the two treatment groups indicating that an initial treatment with G-CSF was not neccessary for a response to the combination. Nine patients in arm B showed a response to the combined treatment, but only three of these responded to epo alone. This suggests a synergistic effect in vivo by G-CSF + epo. A long-term follow-up was made on 71 evaluable patients from both the present and the preceding Scandinavian study on G-CSF + epo. Median survival was 26 months, and the overall risk of leukemic transformation during a median follow-up of 43 months was 28%. Twenty patients entered long-term maintenance treatment and showed a median duration of response of 24 months. The international prognostic scoring system (IPSS) was effective to predict survival, leukemic transformation, and to a lesser extent, duration of response, but had no impact on primary response rates.
使用促红细胞生成素（EPO）治疗可使约20%的骨髓增生异常综合征（MDS）患者的贫血症状得到改善。既往研究表明，联合使用粒细胞集落刺激因子（G-CSF）和EPO进行治疗可能会提高这一缓解率。在本II期研究中，患有MDS和贫血的患者被随机分为两组，按照以下两种方案之一接受G-CSF + EPO治疗：A组先使用G-CSF治疗4周，随后联合治疗12周；B组先使用EPO治疗8周，随后联合治疗10周。该研究纳入了50例可评估患者（10例难治性贫血[RA]、13例环形铁粒幼细胞性难治性贫血[RARS]和27例原始细胞增多的难治性贫血[RAEB]），其中3例仅可评估EPO单药治疗效果，47例可评估联合治疗效果。G-CSF + EPO的总体缓解率为38%，与我们之前的研究相同。RA、RARS和RAEB患者的缓解率分别为20%、46%和37%。两个治疗组的缓解率相同，这表明对于联合治疗的反应，初始使用G-CSF并非必需。B组中有9例患者对联合治疗有反应，但其中只有3例对EPO单药治疗有反应。这表明G-CSF + EPO在体内具有协同作用。对来自本次以及之前斯堪的纳维亚地区关于G-CSF + EPO研究的71例可评估患者进行了长期随访。中位生存期为26个月，在中位随访43个月期间白血病转化的总体风险为28%。20例患者进入长期维持治疗，中位缓解持续时间为24个月。国际预后评分系统（IPSS）可有效预测生存期、白血病转化情况，在一定程度上还可预测缓解持续时间，但对初始缓解率没有影响。
