Abstract
Acute myeloid leukemia (AML) is a phenotypically and prognostically heterogeneous hematopoietic stem cell disease that may be cured in eligible patients with intensive chemotherapy and/or allogeneic stem cell transplantation (allo-SCT). Tremendous advances in sequencing technologies have revealed a large amount of molecular information which has markedly improved our understanding of the underlying pathophysiology and enables a better classification and risk estimation. Furthermore, with the approval of the FMS-like tyrosine kinase 3 (FLT3) inhibitor Midostaurin a first targeted therapy has been introduced into the first-line therapy of younger patients with FLT3-mutated AML and several other small molecules targeting molecular alterations such as isocitrate dehydrogenase (IDH) mutations or the anti-apoptotic b-cell lymphoma 2 (BCL-2) protein are currently under investigation. Despite these advances, many patients will have to undergo allo-SCT during the course of disease and depending on disease and risk status up to half of them will finally relapse after transplant. Here we review the current knowledge about the molecular landscape of AML and how this can be employed to prevent, detect and treat relapse of AML after allo-SCT.
Highlights
Allogeneic stem cell transplantation is besides the use of conventional chemotherapy the second backbone of therapy for patients with acute myeloid leukemia (AML) who are eligible for intensive therapy
As recently reviewed elsewhere [85,120,121], results from these analyses clearly demonstrated that this well-tolerated combination of a HMA and donor cells can induce durable remissions (CR rates ranging from 10% to 75%) and long-term survival in a relevant proportion of patients (2-year survival rates ranging from 12% to 80%)
Our understanding of the molecular heterogeneity and pathophysiology of AML has been greatly advanced by the use of high-throughput sequencing techniques
Summary
Allogeneic stem cell transplantation (allo-SCT) is besides the use of conventional chemotherapy the second backbone of therapy for patients with acute myeloid leukemia (AML) who are eligible for intensive therapy. Despite substantial improvements regarding the reduction of non-relapse mortality during the last decades [2] relapse represents the major cause of treatment failure and up 50% of AML patients relapse after allo-SCT depending on disease status and characteristics [3]. Their prognosis is generally dismal, since many of them, in particular those with early relapse, can either not tolerate or are refractory to low-dose or intensive chemotherapy that are usually applied in this situation. Even with cellular therapies such as donor lymphocyte infusions [4] and second transplantation in selected cases or the use of investigational agents only a minority of patients can be rescued in the long run.
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