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Establishment of hematopoietic cytokine therapy with a combination of hematopoietic factors for hematologic diseases of childhood

造血因子联合治疗儿童血液病的造血细胞因子疗法的建立

基本信息

批准号：
02454269
负责人：
KOMIYAMA Atsushi
金额：
$ 2.37万
依托单位：
Shinshu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1991
项目状态：
已结题

项目摘要

The present studies were conducted to establish hematopoietic cytokine therapy with a combination of hematopoietic factors for hematologic diseases of childhood with cytopenia. To make better hematopoietic cytokine therapy, synergic effects of hematopoietic factors and mechanisms for cytopenia were first studied in anemia of prematurity, aplastic anemia, chronic neutropenia, and acute leukemia. Then., hematopoietic factors (G-CSF, GM-CSF, H-CSF, erythropoietin) were administered in combination.1. Synergic effects of hematopoietic factors in vitro(1) G-CSF and GN-CSF acted synergically on the production of neutrophils.(2) A combination of G-CSF and IL-3 increased the production of neutrophil and monocytes in a synergic fashion.(3) A combination of IL-3 anf IL-6 or IL-3 anf inteferon-gamma had synergic effects on the production of megakaryocytes/platelets.2. Mechanisms for cytopenia in hematologic diseases of childhood(1) In anemia of prematurity, serun erythropoietin levels were low as … More expected based on the hemoglobin concentrations. The erythroid precursors could proliferate and differentiate normally in the presence of erythropoietin.(2) In vitro hematopoiesis was poor in aplastic anemia. The addition of sufficient amounts of hematopoietic factors to thecultures improved the hematopoiesis in some but not in the others.(3) In vitro granulopoiesis was normal in chronic neutropenia. In half of the patients, anti-neutrophil antibodies were detectable, which indicates the involiiement of such antibodies in the neutropenia.3. Hematopoietic cytokine therapy with a combination of hematopoietic factors(1) Erythropoietin was effective for anemia of prematurity. We designed a protocol with a combination of erythropoietin and G-CSF in case of the development of neutropenia as reported by other investigators, but neutropenia did not develop in the patients studied.(2) G-CSF or Gbl-CSF was. effective in five of 1 1 patients with aplastic anemia. Acombination of G-CSF and GM-CSF was effective in two of them.(3) In chronic neutropenia, G-CSF alone yielded satisfactory clinical improvements with a increase in neutrophil counts. After the therapy., anti-neutrophil antibodies decreased in the titer.(4) A combination of G-CSF and M-CSF was effective for intractable mycosis occurred at the neutropenic stage after chemotherapy in acute leukemia. Less

目前的研究旨在建立联合造血因子的造血细胞因子疗法，用于治疗伴有血细胞减少的儿童血液疾病。为了更好地进行造血细胞因子治疗，首先研究了早产儿贫血、再生障碍性贫血、慢性中性粒细胞减少症和急性白血病中造血因子的协同作用和血细胞减少的机制。然后，联合给予造血因子（G-CSF、GM-CSF、H-CSF、促红细胞生成素）。 1．体外造血因子的协同作用（1）G-CSF和GN-CSF协同作用于中性粒细胞的产生。（2）G-CSF和IL-3的组合以协同方式增加中性粒细胞和单核细胞的产生。（3）IL-3与IL-6或IL-3与干扰素-γ的组合具有协同作用。对巨核细胞/血小板产生的协同作用。2．儿童血液疾病中血细胞减少的机制(1) 在早产儿贫血中，血清促红细胞生成素水平低于基于血红蛋白浓度的预期。在促红细胞生成素存在下，红系前体细胞能正常增殖和分化。(2)再生障碍性贫血的体外造血能力较差。在培养物中添加足够量的造血因子可以改善一些细胞的造血功能，但不能改善另一些细胞的造血功能。(3)慢性中性粒细胞减少症的体外粒细胞生成正常。半数患者可检测到抗中性粒细胞抗体，表明该抗体参与中性粒细胞减少症的发生。3．联合造血因子(1)促红细胞生成素治疗早产儿贫血有效。我们设计了一种联合使用促红细胞生成素和 G-CSF 的方案，以应对其他研究人员报告的中性粒细胞减少症的发生，但所研究的患者并未出现中性粒细胞减少症。(2) G-CSF 或 Gbl-CSF 是。对 1 1 再生障碍性贫血患者中的 5 名有效。 G-CSF和GM-CSF联合治疗其中两种情况有效。(3)对于慢性中性粒细胞减少症，单独使用G-CSF可产生令人满意的临床改善，并增加中性粒细胞计数。治疗后抗中性粒细胞抗体滴度下降。(4)G-CSF与M-CSF联合应用对急性白血病化疗后中性粒细胞减少期出现的顽固性真菌病有效。较少的