Laporte J P, Douay L, Allieri A, Lopez M, Dupuy Montbrun M C, Mary J Y, Giarratana M C, Isnard F, Najman A, Gorin N C
Service des Maladies du sang, Hospital Saint Antoine, Paris, France.
Br J Haematol. 1990 Apr;74(4):445-51. doi: 10.1111/j.1365-2141.1990.tb06333.x.
We have tested folinic acid (FA) for ability to increase peripheral blood stem cells (PBSC) after chemotherapeutic aplasia in acute leukaemia. Five adult patients (four AML, one ALL) entered the study, each patient underwent two series of three leukapheresis, the first following induction chemotherapy and the second following the first course of consolidation. The first leukapheresis of each series was done when the white blood cell count reached 10(9)/l with subsequent leukapheresis every other day. Folinic acid (Lederle Laboratories, France) was administered at a dose of 50 mg (i.v.) per day, 15 days from initiation of chemotherapy and continuing through the third leukapheresis of the series (days 25-30). PBSC were collected on a Haemonetics V50 cell separator. In these five cases we observed an increased yield of both colony-forming units, granulocyte macrophage (CFU-GM) and burst forming units-erythroid (BFU-E) expressed per ml of cytapheresis product: CFU-GM x 18, BFU-E x 3 and if expressed per 10(4)/kg of body weight: CFU-GM x 30, BFU-E x 3 (CFU-GM P less than 0.05, BFU-E less than 0.01). Long-term blood culture (LTSC) from FA stimulated leukapheresis, in an attempt to quantitate the most primitive stem cells, demonstrated that this expansion of the PBSC was sustained in time. We found by means of LTSC that FA did not stimulate CFU-L from patients with AML (two cases tested). Finally two AML patients were grafted with FA-PBSC after Cytotoxan and total body irradiation (TBI). Haematopoietic reconstitution was rapid complete and sustained in time in both patients. This indication for folinic acid should be further studied with or as an alternative to haematopoietic growth factors.
我们已经测试了亚叶酸（FA）在急性白血病化疗后再生障碍期增加外周血干细胞（PBSC）的能力。五名成年患者（四名急性髓系白血病患者，一名急性淋巴细胞白血病患者）进入该研究，每位患者接受了两组，每组三次白细胞分离术，第一次在诱导化疗后进行，第二次在第一个巩固疗程后进行。每个系列的第一次白细胞分离术在白细胞计数达到10⁹/L时进行，随后每隔一天进行一次白细胞分离术。亚叶酸（法国莱德利实验室生产）以每天50mg（静脉注射）的剂量给药，从化疗开始后的第15天开始，持续到该系列的第三次白细胞分离术（第25 - 30天）。PBSC通过Haemonetics V50细胞分离器采集。在这五例患者中，我们观察到每毫升血细胞分离产品中集落形成单位、粒细胞巨噬细胞（CFU - GM）和爆式红系集落形成单位（BFU - E）的产量均有所增加：CFU - GM增加了18倍，BFU - E增加了3倍；若按每10⁴/kg体重计算：CFU - GM增加了30倍，BFU - E增加了3倍（CFU - GM，P＜0.05；BFU - E，P＜0.01）。对经FA刺激的白细胞分离术进行长期血液培养（LTSC），试图对最原始的干细胞进行定量分析，结果表明PBSC的这种扩增在一段时间内得以持续。我们通过LTSC发现，FA并未刺激急性髓系白血病患者（测试了两例）的长期培养起始细胞（CFU - L）。最后，两名急性髓系白血病患者在接受环磷酰胺和全身照射（TBI）后，接受了FA - PBSC移植。两名患者的造血重建均迅速、完全且持续了一段时间。对于亚叶酸的这种应用指征，应进一步与造血生长因子联合或作为其替代方法进行研究。
