Abstract
One of the most promising approaches to preventing relapse is the stimulation of the body’s own immune system to kill residual cancer cells after conventional therapy has destroyed the bulk of the tumour. In acute myeloid leukaemia (AML), the high frequency with which patients achieve first remission, and the diffuse nature of the disease throughout the periphery, makes immunotherapy particularly appealing following induction and consolidation therapy, using chemotherapy, and where possible stem cell transplantation. Immunotherapy could be used to remove residual disease, including leukaemic stem cells from the farthest recesses of the body, reducing, if not eliminating, the prospect of relapse. The identification of novel antigens that exist at disease presentation and can act as targets for immunotherapy have also proved useful in helping us to gain a better understand of the biology that belies AML. It appears that there is an additional function of leukaemia associated antigens as biomarkers of disease state and survival. Here, we discuss these findings.
Highlights
Acute Myeloid Leukaemia (AML) is rare in children, but is more commonly observed in adults over the age of 65
We already know a lot about how the immune system works from transplantation studies for AML patients, especially around the importance of graft-versus-host disease (GvHD) to achieve graft-versus-leukaemia (GvL) through twin studies and T cell depletions [10], the boosting of GvHD through repeated donor leukocyte infusion (DLI) transfusions [11] and the role of reduced intensity conditioning allo-transplants to improve the outcomes for older patients [12]
It appears likely that immunotherapy will require use in combination with other treatments, such as hypomethylating agents i.e., SGI-110, a derivative of decitabine [47], which has been shown to lead to the re-expression of melanoma antigen (MAGE)-A and NY-ESO-1 in AML blasts, or more recently treatment in a Phase II clinical trial of AML patients with azacitidine and vorinostat, which led to an increased expression of MAGE, renal cell carcinoma antigen (RAGE), LAGE, synovial sarcoma X breakpoint 2 (SSX2), and taxol resistance associated gene-3 (TRAG3) in blasts, which can be recognised when presented to circulating T cells [48]
Summary
Acute Myeloid Leukaemia (AML) is rare in children, but is more commonly observed in adults over the age of 65. Around 70–80% of AML patients that were aged less than 65 achieve remission through chemotherapy treatment [6], but around half relapse in the absence of stem cell transplantation (SCT). During this period the immune system can recover and residual disease in difficult to reach places could be eliminated by immunotherapy. We already know a lot about how the immune system works from transplantation studies for AML patients, especially around the importance of graft-versus-host disease (GvHD) to achieve graft-versus-leukaemia (GvL) through twin studies and T cell depletions [10], the boosting of GvHD through repeated DLI transfusions [11] and the role of reduced intensity conditioning allo-transplants to improve the outcomes for older patients [12]. To date, the largest improvements in survival remain due to improvements in palliative and supportive care [3]
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