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Title: Prognostic factors in chronic myeloid leukaemia therapy
Author: Ibrahim, Amr Reda Ahmed El Bahy
ISNI:       0000 0004 2715 9863
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2012
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Chronic myeloid leukaemia (CML) is a chronic myeloproliferative disease that is characterized by the presence of the BCR-ABL1 protein, with subsequent increased tyrosine kinase activity. The Introduction of imatinib and second generation tyrosine kinase inhibitors revolutionized CML therapy; however, prognostic factors that can predict disease outcome are still measured using scores that have been developed during the chemotherapy and IFN-α era. This raises the need for modern scores that match the current era. The EUTOS score that has been recently introduced by the ELN promised significant accuracy in determining patients’ outcomes. One drawback however is that the EUTOS score hasn’t been independently validated; hence it failed to predict outcomes in our patient sample. Knowing that the achievement of an early response is an important factor in determining outcomes, we investigated the use of molecular markers as a prognostic factor and we managed to prove that the measurement of transcript levels at 3 months is the single most important factor to determine patients’ outcomes. Current therapy has managed to convert CML into merely a chronic illness in most of the cases, therefore patients and clinicians are faced by problems that are characteristic of long term therapy, including issues of non-adherence and fertility. We managed to show that non-adherence to imatinib can lead to significant loss of responses and treatment failure. We also managed to show that an adequate response is required prior to imatinib interruption for those women who wish to conceive. Unfortunately, not all patients manage to achieve responses on imatinib, and therefore need to change to second line therapy. Funding agencies argue about the survival benefit of second generation TKIs, so here we don’t only show that second generation TKIs offer a survival benefit, but also that the responses achieved on 2G – TKIs are also durable and long lasting. Finally, we explore of the use of TKIs as third line therapy in CML. With future research directed towards the introduction of even better TKIs, especially those targeted against the T315I mutations and vaccination therapy, perhaps in the near future a cure for CML might be achieved.
Supervisor: Marin Costa, David ; Foroni, Letizia Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral