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• W2025705434 abstract "Minimal residual leukaemia (MRL) is due to chemotherapeutic failure. Chemoincurability in chronic myeloid leukaemia and in myelodysplastic syndrome is the norm and is the result of tumour defect arising within the marrow stem cell compartment. We propose that this is indeed the state of affairs in the majority of adult acute leukaemias and such tumours derived from stem cells are chemoincurable. The proportion of acute leukaemias which belong to this category can only be cured by allogeneic bone marrow transplantation though conventional chemotherapy and autotransplant may result in prolonged periods of remission and a return to a preleukaemic state in some patients. A proportion of the acute leukaemias occurring predominantly in children are presently curable by chemotherapy. It is hypothesized that these chemocurable leukaemias derive from the compartment of haemopoietic progenitors already irreversibly committed to a single lineage. Some recent studies using markers of the leukaemic clone to determine the origin of in vitro myeloid colony forming cells support this concept. Intrinsic and/or acquired genetic chemoresistance represents a supplementary restriction to the chemocurability of acute leukaemias. New methods of detecting MRL are sensitive enough to detect up to one leukaemic cell in 106 bone marrow mononuclear cells. However, it is possible that even such sensitive techniques will not be sufficient to determine whether patients in complete remission continue to harbour leukaemic cells in the stem cell compartment when the marker of interest might not be expressed. Furthermore it has been possible with the aid of the polymerase chain reaction to demonstrate the persistence of cells bearing bcr/abl chimeric transcript of the leukaemic clone in long-term survivors after bone marrow transplantation for chronic myeloid leukaemias. Such results raise the question of the biological and clinical significance of MRL. Further aspects of which are discussed by Dr Slavin and coworkers in Chapter 8. Therefore, in order to achieve their great potential therapeutic applications, techniques of detection of MRL should fulfil the following requirements: (a) increase in sensitivity and specificity; (b) development of techniques allowing growth in vitro and/or in SCID mice the residual leukaemic disease; (c) determination of the possible involvement of multilineage stem cell compartment in the leukaemic process. In adult AML and adult ALL we predict this will be the majority of cases; (d) the study of intrinsic and/or acquired chemoresistance of the leukaemic clone. In our view it is necessary to pursue actively ways to overcome drug resistance mechanisms to existing drugs rather than put major effort into development of new conventional drugs. The subsequent judicious use of biological response modifiers, alongside conventional chemotherapy, may lead to better and prolonged haematological remissions. We feel unfortunately that in adult acute leukaemias (AML and ALL) it will be found that the majority of these diseases arise within the stem cell compartment and as Dr Killmann predicted 20 years ago, replacement of that stem cell compartment using newer forms of allogeneic transplant may be the only way forward." @default.
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• W2025705434 title "Concepts of remission, curability and lineage involvement in relationship to the problems of minimal residual leukaemia" @default.
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• W2025705434 doi "https://doi.org/10.1016/s0950-3536(09)90003-8" @default.
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