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Immunotherapy of AML: future directions
  1. Mark W Lowdell1,
  2. Mickey B C Koh1
  1. 1Department of Haematology, Royal Free and University College Medical School (RF Campus), London NW3 2PF, UK
  1. Dr Lowdell email: heg{at}

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The role of the immune response in the control and eradication of leukaemia after allogeneic bone marrow transplantation is established but there is increasing evidence that the principal mechanism of cure after intensive chemotherapy alone is also immune mediated. The idea of a graft versus leukaemia (GvL) effect in eradicating leukaemia was suggested as early as 1957, when Barnes and colleagues1 showed in a murine model that leukaemic animals which received myeloablative radiotherapy followed by syngeneic bone marrow transplant all relapsed with the original acute leukaemia and died; in contrast, animals receiving the same radiotherapy but allogeneic bone marrow transplant all developed fatal graft-versus-host disease (GvHD). However, these latter animals survived longer than the recipients of syngeneic marrow and had no evidence of leukaemia relapse at necropsy. This provided evidence both that myeloablative radiotherapy does not eradicate leukaemia, and that an anti-leukaemia immune response was present. Immune mediated cure of residual leukaemia in the clinical setting has been suggested by observations of a reduced risk of leukaemia relapse after allogeneic bone marrow transplant when compared with autologous or syngeneic bone marrow transplant, and an association between graft-versus-host disease (GvHD) and disease-free survival.2,3 Furthermore, an increased incidence of leukaemia relapse has been reported after aggressive GvHD prophylaxis with cyclosporin or lymphocyte depletion. The most convincing direct evidence of allogeneic antileukaemia activity has been provided by the long lasting remissions following donor leucocyte infusions to treat relapse of chronic myeloid leukaemia (CML) after allogeneic stem cell transplantation.

Specific immunotherapy of acute myeloid leukaemia (AML) is the subject of intense research at present, with major research bodies such as the NIH, the Leukemia Society of America, and the Leukaemia Research Fund supporting large programmes in many centres. The approaches being taken differ widely between groups but can be most readily …

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