How to manage high-risk acute myeloid leukemia

Abstract

There are three general options for management of acute myeloid leukemia (AML): standard therapy, investigational therapy or no treatment other than supportive care. Given AML's natural history and the uncertain results inherent in investigational therapy, most patients intuitively prefer standard therapy, by which is usually meant 3 þ 7 or low-dose cytarabine. However, this preference assumes results with standard therapy are 'satisfactory'. Results with standard therapy of AML are, however, so variable that it is difficult to speak of a single result. Therefore, I review prognostic factors with standard therapy to permit physicians to better inform patients of the likely outcome with such therapy, realizing that the same data might prompt one patient/physician to prefer standard therapy and another investigational therapy under the assumption that although plausibly worse than standard the latter cannot be that much worse. Because even in patients aged 475 years, the principal cause of therapeutic failure is resistance to therapy not treatment-related mortality, I emphasize factors associated with resistance, principally a 'monosomal karyotype' and various molecular markers and extend the European Leukemia Net prognostic system. I also stress the value of waiting for cytogenetic and molecular results before beginning induction therapy and review various investigational options.

CXCR4 Chemokine Receptor Signaling Induces Apoptosis in Acute Myeloid Leukemia Cells via Regulation of the Bcl-2 Family Members Bcl-XL, Noxa, and Bak

“…Relapse is most often mediated by resistance to therapy that is probably driven by the difficulty of eradicating the leukemia stem cells residing within the protected bone marrow microenvironment. Chemotherapeutics are not as effective at targeting the AML cells present in the bone marrow (1,2,61). AMD3100, the CXCR4 antagonist, showed initial promise in removing a large number of AML cells from the bone marrow to the bloodstream, where they could then be targeted by the chemotherapeutics.…”

Low-dose lenalidomide plus cytarabine induce complete remission that can be predicted by genetic profiling in elderly acute myeloid leukemia patients

“…Intensive induction chemotherapy is often unsuitable. 1 High-dose lenalidomide is effective in AML, alone 2,3 or in combination with azacitidine. [4][5][6] Biomarkers that are able to predict response to lenalidomide would be extremely useful.…”

“…Bone marrow evaluation was performed after 1, 2, 4 and 6 cycles. Responding patients experiencing a non-hematological toxicity 42 WHO received reduced courses (lenalidomide (10 mg) once daily (days [1][2][3][4][5][6][7][8][9][10][11][12][13][14], and cytarabine (10 mg, subcutaneously) twice daily (days 1-10)). All patients were hospitalized for the first cycle.…”

“…To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/ Supplementary Information accompanies this paper on the Leukemia website (http://www.nature.com/leu) MSC-derived exosomes: a novel tool to treat therapy-refractory graft-versus-host disease Approximately 35-50% of the patients receiving matched related or unrelated allogeneic stem cell transplantation, develop severe forms of graft-versus-host disease (GvHD; Grade II-IV) that cannot be controlled with corticosteroids in up to 50% of the GvHD patients. 1 Owing to the lack of confirmed treatment options Le Blanc et al 2 introduced mesenchymal stem cells (MSCs) as a strategy to treat severe therapy-refractory acute GvHD. Since then, a number of different studies have addressed the impact of MSC administration on GvHD with different outcomes.…”

CD30 Expression vs. Serum Soluble CD30 (sCD30) Level: Role in Prognosis and Treatment of Acute Myeloid Leukaemia

“…AML in old age [2], secondary to myeloproliferative neoplasms (MPN) or myelodysplastic syndromes (MDS), accompanied with high-risk cytogenetics responds unwell to routine treatment. Relapsed or refractory AML is usually anticipated as an untreatable illness [3].…”