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

本研究旨在建立联合造血因子治疗儿童血液病伴细胞减少症的方法。为了更好地进行造血细胞因子治疗，我们首先研究了造血因子在早产儿贫血、再生障碍性贫血、慢性中性粒细胞减少症和急性白血病中的协同作用和细胞减少的机制。然后。联合给予造血因子（G-CSF、GM-CSF、H-CSF、促红细胞生成素）。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的联合作用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的联合作用对巨核细胞/血小板的产生具有协同作用。儿童血液病中细胞减少的机制(1)在早产儿贫血中，血清促红细胞生成素水平低于…红细胞前体在促红细胞生成素的作用下能够正常增殖和分化。(2)再生障碍性贫血患者体外造血功能较差。在培养物中加入足量的造血因子可以改善一些细胞的造血功能，但在另一些细胞中则没有。(3)慢性中性粒细胞减少症患者体外粒细胞生成正常。在一半的患者中，检测到抗中性粒细胞抗体，这表明这种抗体参与了中性粒细胞减少症。(1)促红细胞生成素治疗早产儿贫血有效。我们设计了一种方案，结合促红细胞生成素和G-CSF，以防止其他研究者报道的中性粒细胞减少症的发生，但在研究的患者中没有发生中性粒细胞减少症。(2) G-CSF或Gbl-CSF。11例再生障碍性贫血患者中5例有效。G-CSF与GM-CSF合用对其中2例均有效。(3)在慢性中性粒细胞减少症中，单独使用G-CSF可获得令人满意的临床改善，中性粒细胞计数增加。在治疗之后。抗中性粒细胞抗体滴度下降。(4) G-CSF联合M-CSF治疗急性白血病化疗后中性粒细胞减少期难治性真菌病有效。少

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