Hehlmann R, Berger U, Pfirrmann M, Hochhaus A, Metzgeroth G, Maywald O, Hasford J, Reiter A, Hossfeld D K, Kolb H-J, Löffler H, Pralle H, Queisser W, Griesshammer M, Nerl C, Kuse R, Tobler A, Eimermacher H, Tichelli A, Aul C, Wilhelm M, Fischer J T, Perker M, Scheid C, Schenk M, Weiss J, Meier C R, Kremers S, Labedzki L, Schmeiser T, Lohrmann H-P, Heimpel H
Klinikum Mannheim, Universität Heidelberg, Mannheim, Germany.
Leukemia. 2003 Aug;17(8):1529-37. doi: 10.1038/sj.leu.2403006.
The optimum treatment conditions of interferon (IFN) alpha therapy in chronic myeloid leukemia (CML) are still controversial. To evaluate the role of hydroxyurea (HU) for the outcome of IFN therapy, we conducted a randomized trial to compare the combination of IFN and HU vs HU monotherapy (CML-study II). From February 1991 to December 1994, 376 patients with newly diagnosed CML in chronic phase were randomized. In all, 340 patients were Ph/BCR-ABL positive and evaluable. Randomization was unbalanced 1:2 in favor of the combination therapy, since study conditions were identical to the previous CML-study I and it had been planned in advance to add the HU patients of study I (n=194) to the HU control group. Therefore, a total of 534 patients were evaluable (226 patients with IFN/HU and 308 patients with HU). Analyses were according to intention-to-treat. Median observation time of nontransplanted living patients was 7.6 years (7.9 years for IFN/HU and 7.3 years for HU). The risk profile (new CML score) was available for 532 patients: 200 patients (38%) were low, 239 patients (45%) intermediate, and 93 patients (17%) high risk. Complete hematologic response rates were higher in IFN/HU-treated patients (59 vs 32%). Of 169 evaluable IFN/HU-treated patients (75%), 104 patients (62%) achieved a cytogenetic response that was complete in 12% (n=21), major in 14% (n=24), and at least minimal in 35% (n=59). Of the 534 patients, 105 (20%) underwent allogeneic stem cell transplantation in first chronic phase. In the low-risk group, 65 of 200 patients were transplanted (33%), 30 (13%) in the intermediate-risk group, and nine (10%) in the high-risk group. Duration of chronic phase was 55 months for IFN/HU and 41 months for HU (P<0.0001). Median survival was 64 months for IFN/HU and 53 months for HU-treated patients (P=0.0063). We conclude that IFN in combination with HU achieves a significant long-term survival advantage over HU monotherapy. In view of the data of CML-study I, these results suggest that IFN/HU is also superior to IFN alone. HU should be combined with IFN in IFN-based therapies and for comparisons with new therapies.
干扰素（IFN）α治疗慢性粒细胞白血病（CML）的最佳治疗条件仍存在争议。为评估羟基脲（HU）对IFN治疗结果的作用，我们进行了一项随机试验，比较IFN与HU联合治疗和HU单药治疗（CML研究II）。1991年2月至1994年12月，376例新诊断的慢性期CML患者被随机分组。共有340例患者Ph/BCR-ABL阳性且可评估。随机分组不均衡，为1:2倾向于联合治疗，因为研究条件与之前的CML研究I相同，且事先计划将研究I中的HU患者（n = 194）加入HU对照组。因此，共有534例患者可评估（226例接受IFN/HU治疗，308例接受HU治疗）。分析按照意向性治疗原则进行。未移植存活患者的中位观察时间为7.6年（IFN/HU组为7.9年，HU组为7.3年）。532例患者有风险评估（新CML评分）：200例患者（38%）为低风险，239例患者（45%）为中风险，93例患者（17%）为高风险。IFN/HU治疗组的完全血液学缓解率更高（59%对32%）。在169例可评估的IFN/HU治疗患者中（75%），104例患者（62%）获得了细胞遗传学缓解，其中完全缓解的占12%（n = 21），主要缓解的占14%（n = 24），至少微小缓解的占35%（n = 59）。534例患者中，105例（20%）在慢性期首次接受了异基因干细胞移植。在低风险组中，200例患者中有65例接受了移植（33%），中风险组中有30例（13%），高风险组中有9例（10%）。IFN/HU组慢性期持续时间为55个月，HU组为41个月（P<0.0001）。IFN/HU治疗患者的中位生存期为64个月，HU治疗患者为53个月（P = 0.0063）。我们得出结论，IFN与HU联合治疗相对于HU单药治疗具有显著的长期生存优势。鉴于CML研究I的数据，这些结果表明IFN/HU也优于单独使用IFN。在基于IFN的治疗中以及与新疗法进行比较时，HU应与IFN联合使用。
