Haemopoietic progenitor and myeloid cell kinetics in humans treated with interleukin-3 and granulocyte/macrophage colony-stimulating factor in combination.
AuthorsLord, Brian I
Testa, Nydia G
Coutinho, Lucia H
De Campos, E S
Scarffe, J Howard
AffiliationDepartment of Experimental Haematology, PICR, Manchester, UK.
MetadataShow full item record
AbstractPatients with advanced adenocarcinoma of the colon, rectum or pancreas were entered into trials for evaluation of treatment with sequential doses of IL-3 and GM-CSF. They received 0.25 to 5 micrograms IL-3/kg/d for up to 7 days, followed by 1 microgram GM-CSF/kg/day for a maximum of 10 further days. We assessed the kinetics of bone-marrow cell proliferation and of blood production using tritiated thymidine labelling in vitro and in vivo. Megakaryocytic-CFC were unaffected but proliferation rates of GM-CFC and BFU-E were increased. Progenitor cells were mobilized (12-fold over baseline) into the peripheral blood. The proliferative activity of maturing cells in the marrow was increased (cell-cycle times were reduced by at least 30%). This translated into amplified blood cell production (WCC approximately 30 x 10(9)/l), a 2.2-fold increase in platelet counts and significant eosinophilia. Newly generated neutrophils appeared in the circulation at the normal time and their peripheral half-life was also normal. The calculated 3.2-fold amplification in neutrophil production required nearly 2 extra divisions in the marrow, shared between the progenitors and the proliferating granulocytic cells. The results were compared with those of a previous trial using GM-CSF only, although at a 10-fold higher dose level. Comparable levels of peripheral neutrophils were obtained in both trials but significant ineffective granulopoiesis developed in the earlier study. This was overcome in the present study, the priming dose of IL-3 apparently giving the latitude to utilize lower doses of GM-CSF with less risk of complications.
CitationHaemopoietic progenitor and myeloid cell kinetics in humans treated with interleukin-3 and granulocyte/macrophage colony-stimulating factor in combination. 1994, 59 (4):483-90 Int. J. Cancer
JournalInternational Journal of Cancer
- Myeloid cell kinetics in response to haemopoietic growth factors.
- Authors: Lord BI
- Issue date: 1992 Jul
- Proliferative response of human marrow myeloid progenitor cells to in vivo treatment with granulocyte colony-stimulating factor alone and in combination with interleukin-3 after autologous bone marrow transplantation.
- Authors: Lemoli RM, Fortuna A, Fogli M, Gherlinzoni F, Rosti G, Catani L, Gozzetti A, Miggiano MC, Tura S
- Issue date: 1995 Dec
- Interleukin-3 followed by GM-CSF for delayed engraftment after autologous bone marrow transplantation.
- Authors: Crump M, Couture F, Kovacs M, Saragosa R, McCrae J, Brandwein J, Huebsch L, Beauregard-Zollinger L, Keating A
- Issue date: 1993 Mar
- Effects of in vivo treatment with PIXY321 (GM-CSF/IL-3 fusion protein) on proliferation kinetics of bone marrow and blood myeloid progenitor cells in patients with sarcoma.
- Authors: Broxmeyer HE, Benninger L, Cooper S, Hague N, Benjamin RS, Vadhan-Raj S
- Issue date: 1995 Apr
- Comparative effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) on priming peripheral blood progenitor cells for use with autologous bone marrow after high-dose chemotherapy.
- Authors: Peters WP, Rosner G, Ross M, Vredenburgh J, Meisenberg B, Gilbert C, Kurtzberg J
- Issue date: 1993 Apr 1