Dombret H, Geiger S, Daniel M T, Glaisner S, Micléa J M, Castaigne S, Merle-Beral H, Lacombe C, Chomienne C, Degos L
Service Clinique des Maladies du Sang, Hôpital Saint-Louis, Paris, France.
Leukemia. 1995 Sep;9(9):1473-7.
According to French and European experience, hyperleukocytosis occurs during ATRA differentiation therapy in about 70% of de novo and 25% of relapsed APL cases. The most frequently suggested cause for this side-effect is an ATRA-induced proliferation of APL cells. However, no definite explanation for such a proliferative effect has been clearly established. Another mechanism directly related to the differentiation of marrow leukemic cells could be a change in their microrheology, allowing their release from the bone marrow and their transfer toward peripheral blood (PB) and tissues. Using a single cell aspiration assay into a glass restrictive channel, we measured APL cell viscosity values in five de novo APL patients. A deformability index (DI) was defined as the ratio of mean normal neutrophil viscosity x 100/mean APL cell viscosity. Results were the following: (1) at diagnosis, two patients had high marrow DI (96 and 250%) and three patients had low marrow DI (16, 17, and 40%); (2) when PB and marrow APL cells were simultaneously tested, PB APL cells display higher DI than marrow APL-cells; (3) the two patients with high initial marrow DI experienced an ATRA-induced hyperleukocytosis after only 1 day of treatment; (4) in the three patients with low initial marrow DI, the DI was increasing during ATRA therapy and hyperleukocytosis seemed to occur when a large amount of maturing APL cells reached a viscosity value similar to that of mature neutrophils. These results suggest that an asynchronism between rheological and morphological maturation in each APL cell might explain the occurrence of hyperleukocytosis in some patients during ATRA differentiation therapy.
根据法国和欧洲的经验，在全反式维甲酸（ATRA）分化治疗期间，约70%的初发急性早幼粒细胞白血病（APL）病例及25%的复发APL病例会出现白细胞增多症。对于这种副作用，最常被提及的原因是ATRA诱导的APL细胞增殖。然而，对于这种增殖效应，尚未明确确立确切的解释。另一种与骨髓白血病细胞分化直接相关的机制可能是其微观流变学的改变，使得它们能够从骨髓中释放出来，并转移至外周血（PB）和组织中。我们使用单细胞吸入测定法，将细胞吸入玻璃限制通道，测量了5例初发APL患者的APL细胞粘度值。定义了一个变形性指数（DI），即平均正常中性粒细胞粘度×100/平均APL细胞粘度的比值。结果如下：（1）诊断时，2例患者骨髓DI较高（分别为96%和250%），3例患者骨髓DI较低（分别为16%、17%和40%）；（2）同时检测外周血和骨髓中的APL细胞时，外周血APL细胞的DI高于骨髓APL细胞；（3）2例初始骨髓DI较高的患者在治疗仅1天后就出现了ATRA诱导的白细胞增多症；（4）在3例初始骨髓DI较低的患者中，ATRA治疗期间DI逐渐升高，当大量成熟的APL细胞达到与成熟中性粒细胞相似的粘度值时，似乎会出现白细胞增多症。这些结果表明，每个APL细胞的流变学成熟和形态学成熟之间的不同步可能解释了某些患者在ATRA分化治疗期间白细胞增多症的发生。
