Silverman L R, Holland J F, Weinberg R S, Alter B P, Davis R B, Ellison R R, Demakos E P, Cornell C J, Carey R W, Schiffer C
Mount Sinai Hospital, New York, NY.
Leukemia. 1993 May;7 Suppl 1:21-9.
The myelodysplastic syndrome (MDS) comprises a group of clonal hematopoietic disorders derived from an abnormality affecting a multipotent hematopoietic stem cell. Despite trials testing numerous agents in patients with MDS, no single drug has yet emerged as the accepted standard of treatment. Observation and supportive care with blood products and antibiotics, when necessary, continue to be the mainstays of therapy. We administered 5-azacytidine, a cell-cycle specific ring analog of the pyrimidine nucleoside cytosine, as a continuous intravenous infusion, 75 mg/m2 per day for 7 days every 4 weeks. Patients had refractory anemia with excess blasts (RAEB) or refractory anemia with excess blasts in transformation (RAEB-T). Responses were seen in 21 (49%) of 43 evaluable patients: five (12%) in complete remission (CR, complete normalization of bone marrow and peripheral blood counts); 11 (25%) in partial remission (PR, > or = 50% restoration of the deficit from normal of all three peripheral blood cell lines, elimination of transfusion requirements, and a decrease in percentage bone marrow blasts by > or = 50% from prestudy values); five (12%) improved (> or = 50% restoration in the deficit from normal of one or more peripheral blood cell lines and/or a > or = 50% decrease in transfusion requirements). A trilineage improvement (CR and PR) occurred in 37% of the patients. The median survival for all patients was 13.3 months and the median duration of remission for those with CR and PR was 14.7 months. Mild to moderate nausea and/or vomiting was the most common side effect (63%). Myelosuppression, either bone marrow hypoplasia or drug related cytopenias requiring a reduction in the dose of azacitidine, occurred in only 33% of the patients. Prior to treatment, bone marrow erythroid progenitor cells were assayed in vitro. Colonies derived from erythroid burst-forming units (BFU-e) were undetectable in one patient and reduced in two. The number of colonies derived from erythroid colony-forming units (CFU-e)) were also reduced in two of the three patients. In the two patients with detectable colony growth prior to treatment, colony number decreased by day 8 of the first cycle, followed by a subsequent increase. Continued treatment with azacitidine led to normalization of the number of CFU-e derived colonies as well as an increase in the number of BFU-e derived colonies. This improvement in erythroid colony number correlated with the spontaneous rise in hemoglobin levels and red cell transfusion independence.(ABSTRACT TRUNCATED AT 400 WORDS)
骨髓增生异常综合征（MDS）是一组源于多能造血干细胞异常的克隆性造血疾病。尽管对MDS患者进行了多种药物试验，但尚无单一药物成为公认的治疗标准。观察以及必要时使用血液制品和抗生素进行支持性护理仍是主要治疗手段。我们给予5-氮杂胞苷，它是嘧啶核苷胞嘧啶的一种细胞周期特异性环状类似物，通过持续静脉输注给药，剂量为75mg/m²，每天1次，共7天，每4周重复1次。患者为伴有过多原始细胞的难治性贫血（RAEB）或转化中的伴有过多原始细胞的难治性贫血（RAEB-T）。43例可评估患者中有21例（49%）出现反应：5例（12%）完全缓解（CR，骨髓和外周血细胞计数完全恢复正常）；11例（25%）部分缓解（PR，所有三种外周血细胞系从正常水平恢复至少50%的缺失，无需输血，骨髓原始细胞百分比较研究前值降低至少50%）；5例（12%）病情改善（一种或多种外周血细胞系从正常水平恢复至少50%的缺失和/或输血需求降低至少50%）。37%的患者出现三系改善（CR和PR）。所有患者的中位生存期为13.3个月，CR和PR患者的中位缓解持续时间为1个月。轻度至中度恶心和/或呕吐是最常见的副作用（63%）。骨髓抑制，即骨髓发育不全或需要降低阿扎胞苷剂量的药物相关性血细胞减少，仅发生在33%的患者中。治疗前，对骨髓红系祖细胞进行了体外检测。1例患者未检测到源自红系爆式集落形成单位（BFU-e）的集落，2例患者其数量减少。源自红系集落形成单位（CFU-e）的集落数量在3例患者中的2例也减少。在治疗前集落生长可检测的2例患者中，第一个周期第8天时集落数量减少，随后增加。持续使用阿扎胞苷治疗导致CFU-e衍生集落数量恢复正常以及BFU-e衍生集落数量增加。红系集落数量的这种改善与血红蛋白水平的自发升高和红细胞输注独立性相关。（摘要截短至400字）
