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The effect of high dose chemotherapy on hemopoietic colony stimulating activity in the plasma of patients with multiple myeloma

Joffe, Jonathan Keith; (1994) The effect of high dose chemotherapy on hemopoietic colony stimulating activity in the plasma of patients with multiple myeloma. Doctoral thesis (M.D), UCL (University College London). Green open access

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Abstract

Following intensive chemotherapy with high dose melphalan (HDM), plasma from patients with multiple myeloma (MM) has been tested for the presence of activity that can promote the growth of granulocyte-macrophage colonies (GM-CFUc) from normal human bone marrow mononuclear cells (BMMNC) in-vitro. Colony stimulating activity (CSA) in plasma has been compared with the recovery of peripheral blood leucocytes, platelets and haemopoietic progenitors (PB GM-CFUc). The presence of individual cytokines in plasma has been determined by the use of enzyme-linked immunoabsorbent assays (ELISA) and radioimmunoassy (RIA). Peripheral blood GM-CFUc and CSA decreased after a priming dose of cyclophosphamide given before HDM, but numbers of GM-CFUc in the bone marrow increased in the same individuals. Numbers of PB GM-CFUc before priming predicted numbers of GM-CFUc that could be harvested from patients bone marow 5-9 days later. After HDM, CSA increased and was independent of disease status, previous chemotherapy, the use of autologous bone marrow rescue (ABMR) or recombinant human granulocyte colony stimulating factor (rhG-CSF). CSA was not related to the acute phase response, as indicated by a lack of correlation with changes in plasma levels of interleukins 1 or 6 (IL-1 or IL-6) or C-reactive protein, but was correlated with the development and duration of leucopenia after treatment. Interleukin-4 (IL-4) could augment plasma CSA in-vitro and this was shown to be due to the presence of endogenous G-CSF. Interleukin-3 (IL-3) and GM-CSF (granulocyte-nnacrophage-CSF) were not detected in plasma but CSA could be inhibited in-vitro by the addition of antibody to GM-CSF. The origins and physiology of CSA are discussed with reference to results that suggest that this activity does not arise from haemopoietic tissue.

Type: Thesis (Doctoral)
Qualification: M.D
Title: The effect of high dose chemotherapy on hemopoietic colony stimulating activity in the plasma of patients with multiple myeloma
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences; Health and environmental sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10106536
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