Dover G J, Charache S
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Prog Clin Biol Res. 1987;251:455-66.
Five years experience using 5AZA and HU in a limited number of patients with SS disease, have resulted in the following conclusions. First, these drugs can rapidly induce increases in HbF production. Rapid increases in HbF production are not associated with reductions in overall reticulocyte levels, or reductions in late erythroid precursors, such as CFU-E. Indeed, where higher doses of these drugs are used or where the patient is unable to clear the drug rapidly, cytotoxicity is associated with reduced HbF production. These drugs not only increase the number of cells containing HbF, but also increase the MCV and the MCH of both F cells and non-F cells. Uncontrolled clinical trials suggest that the clinical severity of the disease measured by reduction in anemia and fewer vasoocclusive SS crises, may result from use of these drugs. The mechanisms by which these drugs result in increased F-cell production and increased MCH of F cells and non-F cells, may be due to their ability to reversibly block cells during their cell-cycle. This reversible blockade does not inhibit either on-going protein production or the establishment of origins of replications of DNA. Even though the mechanisms whereby the increased HbF production is not known, early clinical results seem to justify the initiation of controlled clinical trials of HU in severely affected SS patients.
在数量有限的镰状细胞贫血（SS）病患者中使用5-氮杂胞苷（5AZA）和羟基脲（HU）的五年经验得出了以下结论。首先，这些药物可迅速诱导胎儿血红蛋白（HbF）生成增加。HbF生成的快速增加与总体网织红细胞水平的降低或晚期红系前体细胞（如红细胞集落形成单位 - 红系，CFU - E）的减少无关。实际上，在使用较高剂量这些药物的情况下，或者在患者无法迅速清除药物的情况下，细胞毒性与HbF生成减少相关。这些药物不仅增加了含有HbF的细胞数量，还增加了F细胞和非F细胞的平均红细胞体积（MCV）和平均红细胞血红蛋白含量（MCH）。非对照临床试验表明，通过贫血减轻和血管闭塞性SS危象减少来衡量的疾病临床严重程度的改善，可能源于这些药物的使用。这些药物导致F细胞生成增加以及F细胞和非F细胞的MCH增加的机制，可能是由于它们在细胞周期中可逆地阻滞细胞的能力。这种可逆性阻滞既不抑制正在进行的蛋白质合成，也不抑制DNA复制起点的建立。尽管HbF生成增加的机制尚不清楚，但早期临床结果似乎证明对重症SS患者启动HU对照临床试验是合理的。
