|Budget Amount *help
¥5,200,000 (Direct Cost : ¥5,200,000)
Fiscal Year 1993 : ¥1,200,000 (Direct Cost : ¥1,200,000)
Fiscal Year 1992 : ¥4,000,000 (Direct Cost : ¥4,000,000)
The present studies were conducted to establish hemopoietic cytokine therapy with a combination of hemopoietic factors for thrombocytopenia in several hematologic/neoplastic disorders of childhood. To make the better hemopoietic cytokine therapy, synergic effects of hemopoietic factors on the thrombopoiesis were first studied in the mouse and human culture systems using IL-3, IL-6, IL-11, G-CSF, GM-CSF, M-CSF, erythropoietin (EPO) and stem cell factor (SCF). Then, several combinations of hemopoietic factors were administered in children with aplastic anemia or acute leukemia.
1. Synergic effects of hemopoietic factors in vitro
(1) The stimulatory effects of IL-6 and IL-11 on the megakaryocyte colony formation were augmented by the addition of IL-3 in the mouse culture system.
(2) In the human culture system, IL-6, IL-11 or SCF alone did not have the stimulatory effects on the megakaryocyte growth. When SCF was combined with IL-6 or IL-11, there was significant formation of megakaryocyte colonies. These results were confirmed in the experiments using CD34+ cells.
(3) SCF had stimulatory effects on the proliferation of primitive megakaryocytic progenitors (megakaryocyte colony-stimulating factor) but not on the maturation of megakaryocytes (megakaryocyte potentiator). Thus, SCF should be administered in the clinical use in combination with such megakaryocyte potentiators as IL-6 and IL-11.
(4) IL-3, IL-6, IL-11, GM-CSF, M-CSF or EPO alone or in combination could increase the megakaryocyte colony formation in some children with aplastic anemia.
2. Hemopoietic cytokine therapy for thrombocytopenia
(1) The administration of G-CSF, G-CSF + GM-CSF or G-CSF + EPO increased the number of platelets in some patients with aplastic anemia.
(2) The effect of EPO to increase platelet counts was confirmed in the EPO therapy for anemia of prematurity.