Gerhartz H H, Marcus R, Delmer A, Zwierzina H, Suciu S, Dardenne M, Solbu G, de Witte T, Jacobs A, Visani G
Medical Dept. III, Klinikum Grosshadern, Munich, Germany.
Leukemia. 1994 Jan;8(1):16-23.
In a randomized phase II study, patients with myelodysplastic syndromes (MDS) with 10-30% blasts in the bone marrow and hematopoietic failure were treated with low-dose Ara C (2 x 10 mg/m2 subcutaneously (s.c.) days 1-14) and rhGM-CSF (fully glycosylated, Sandoz/Schering-Plough, 2 x 150 micrograms protein/day s.c.) given either following Ara C (days 15-21) or simultaneously (days 8-14) for 1-5 cycles. 108 patients with a median age of 65 years, range 17-80 years and refractory anemia with an excess of blasts (RAEB, n = 54), RAEB with transformation (RAEBt, n = 50) or with chronic myelomonocytic leukemia (CMML, n = 4) were evaluable. Complete remission was achieved in 15 cases (14%), 11 had a partial response (10%), and 16 a minor response (15%). Stable disease was reached in 35 cases (32%). There were 16 cases of toxic death (15%), progression occurred in 15 patients (14%). No differences existed between the two treatment arms with respect to response and duration of response. Prognostic factors for poor response included the presence of cytogenetic abnormalities and a history of previous blood transfusions. Major adverse events during treatment were hemorrhage (55%), infections (54%), and fever associated with GM-CSF administration (40%). The overall response rate ws 39%, median duration was 12.5 months from start of treatment which allowed responding patients to lead good quality life without further therapy. The question whether the combination is indeed superior to LD-Ara C alone is not settled but will be evaluated in an ongoing clinical trial.
在一项随机II期研究中，对骨髓中原始细胞占10%-30%且存在造血功能衰竭的骨髓增生异常综合征（MDS）患者，采用小剂量阿糖胞苷（第1 - 14天皮下注射2×10 mg/m²）联合重组人粒细胞巨噬细胞集落刺激因子（完全糖基化，山德士/先灵葆雅生产，每天皮下注射2×150微克蛋白）进行治疗，重组人粒细胞巨噬细胞集落刺激因子在阿糖胞苷治疗后（第15 - 21天）或同时（第8 - 14天）给药，共进行1 - 5个周期。108例患者可进行评估，中位年龄65岁，年龄范围17 - 80岁，其中难治性贫血伴原始细胞增多（RAEB，n = 54）、转化型RAEB（RAEBt，n = 50）或慢性粒单核细胞白血病（CMML，n = 4）。15例（14%）达到完全缓解，11例部分缓解（10%），16例微小缓解（15%）。35例（32%）病情稳定。16例（15%）出现毒性死亡，15例（14%）病情进展。两个治疗组在缓解率和缓解持续时间方面无差异。缓解不佳的预后因素包括细胞遗传学异常的存在以及既往输血史。治疗期间的主要不良事件为出血（55%）、感染（54%）以及与重组人粒细胞巨噬细胞集落刺激因子给药相关的发热（40%）。总体缓解率为39%，从治疗开始的中位持续时间为12.5个月，这使得缓解患者无需进一步治疗即可过上高质量生活。联合治疗是否确实优于单独使用小剂量阿糖胞苷的问题尚未解决，但将在一项正在进行的临床试验中进行评估。
