Grant-in-Aid for General Scientific Research (B)
|Allocation Type||Single-year Grants|
|Research Institution||Shinshu University|
KOMIYAMA Atsushi Shinshu Univ. School Med., Dept. Pediatrics, Professor, 医学部, 教授 (50020798)
KOIKE Kenichi Shinshu Univ. School Med., Dept. Pediatrics, Assistant Professor, 医学部, 講師 (40143979)
KAWAI Hiroshi Shinshu Univ. School Med., Dept. Pediatrics, Assistant Professor, 医学部附属病院, 講師 (70126671)
|Project Period (FY)
1990 – 1991
Completed(Fiscal Year 1991)
|Budget Amount *help
¥3,700,000 (Direct Cost : ¥3,700,000)
Fiscal Year 1991 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Fiscal Year 1990 : ¥2,700,000 (Direct Cost : ¥2,700,000)
|Keywords||hematopoietic factors / erythropoietin / colony-stimulating factor / anemia of prematurity / aplastic anemia / neutropenia / leukemia|
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
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