Serum colony stimulating factors in patients undergoing bone marrow transplantation: enhancing effect of recombinant human GM-CSF.
Sera from 11 patients undergoing autologous or allogeneic BMT were tested for their content of megakaryocytic, granulocytic and erythrocytic colony stimulating factors. During the first week after BMT, all patients sera revealed a low/inadequate production of granulocytic, erythrocytic and megakaryocytic colony-stimulating activity (defined as the number of colonies per plate induced by 30% test serum from monocyte and T-lymphocyte depleted bone marrow cells). Thereafter an increase of colony-stimulating activity for all cell lineages tested was observed with peak levels between days 8 to 14 after BMT. The peak level was followed by a decline of colony stimulating activity, which shows an inverse correlation to basal blood leukocyte counts suggesting an adequate counter-regulation during this period. The GM colonies grown in the presence of patient serum were found to consist largely of neutrophilic granulocytes with only single monocytic colony, but without eosinophilic colony formation, suggesting that granulopoietic colony formation during this period is mediated predominantly by G-CSF and not by GM-CSF. All patients undergoing autologous BMT revealed a low/inadequate endogenous CSF production. rh GM-CSF addition in vitro was able to compensate from the impaired endogenous granulopoietic CSA in all patients and resulted in a constant augmentation of granulopoietic colony formation. The percentage of eosinophilic colony formation showed an inverse correlation to endogenous CSF production also suggesting that G-CSF is secreted during this period. In contrast to the granulopoietic colony formation, erythropoietic and megakaryopoietic colony formation was not enhanced by GM-CSF addition in vitro and even showed a slight reduction in some experiments. Our results suggest the treatment with recombinant GM-CSF might be beneficial for a faster reconstitution of granulo-monocytopoiesis after BMT, that rh GM-CSF therapy should be started immediately after bone marrow transplantation and that G-CSF is the main factor secreted in allogeneic bone marrow transplantations in the regeneration period.
Geissler
D
D
Department of Internal Medicine, University Hospitals, Innsbruck, Austria.
Niederwieser
D
D
Aulitzky
W E
WE
Tilg
H
H
Grünewald
K
K
Huber
C
C
Konwalinka
G
G
D016026:Bone Marrow Transplantation; D002449:Cell Aggregation; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000097:blood* / Q000502:physiology / Q000627:therapeutic use*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000502:physiology / Q000627:therapeutic use*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D012016:Reference Values; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects; D014184:Transplantation, Homologous
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor