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Title: Peripheral blood stem cells in haematological malignancies
Author: Craig, Jenny I. O.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1991
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Autologous bone marrow transplantation is used successfully as intensive therapy for patients with haematological malignancies and other solid tumours. Peripheral blood contains haematopoietic progenitors whose levels are greatly increased during very early remission after treatment for acute leukaemia or after high dose chemotherapy schedules. These circulating progenitors have been harvested by leucapheresis and used as an alternative to bone marrow as salvage after myeloablative treatments. Peripheral blood stem cells (PBSC) appear to have several advantages over bone marrow including rapid haematopoietic reconstitution after transplantation, the ability to collect PBSC without a general anaesthetic and in the presence of bone marrow abnormalities and the possibility of minimal tumour contamination. My aims were 1) to establish the response of PBSC, measured by the CFU-GM assay, to standard chemotherapy regimes with particular reference to patients with lymphoma, 2) to assess our ability to harvest these progenitors by leukapheresis when numbers were raised and 3) to determine tumour infiltration in PBSC harvests using Southern blotting techniques. Circulating CFU-GM were studied sequentially in 64 patients (40 female, 24 male) 24 non-Hodgkin's lymphoma (NHL), 22 Hodgkin's disease (HD), 9 acute myeloid leukaemia (AML), 5 acute lymphoblastic leukaemia (ALL) and 4 myeloma. Three patients with NHL receiving ALL type therapy showed a mean increase in CFU-GM 15.6 fold over normal values occurring on day 21. Eighteen received CHOP based regimes and demonstrated a 6.2 fold rise between days 15-28. PEEC increased progenitors 43 fold, however CVP and VAD only raised CFU-GM by 2.9 and 2.4 fold respectively. In those patients wth HD a 14.5 fold increase in PBSC was induced in the 4 patients treated with HOPE-bleo. ABVD and MOPP raised peak values to 2.8 and 3.5 times normal and ChlVPP produced a 2.9 fold increase. In the lymphoma group as a whole, standard chemotherapy failed to mobilise PBSC in 15% of patients. Significantly lower peak CFU-GM were found in those who had received previous chemotherapy or who had marrow involvement with disease.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available