Therapeutic options for acute myelogenous leukemia

Abstract

BACKGROUND General therapeutic options for patients with acute myelogenous leukemia (AML) are reviewed and specific new therapies are described. METHODS Data in this review came from the published literature and the M. D. Anderson Cancer Center's acute leukemia database. RESULTS Outcome following standard therapy of AML is so variable that is best to speak of a range of outcomes determined by various prognostic factors. Therapy can (and usually does) fail because of treatment‐induced mortality or (more usually) resistance to therapy. Performance status and age are the principal predictors of early death, whereas cytogenetics, a history of abnormal blood counts, and MDR1 expression are predictors of resistance. Using this information, physicians can categorize patients into those in whom 1) standard therapy is indicated, 2) either standard or investigational therapy is appropriate, and 3) investigational therapy is indicated. The majority of even newly diagnosed patients belong to Group 3. The availability of allogeneic or autologous transplantation does not alter this conclusion. Investigational therapies have been developed that are directed against the CD33 surface antigen, the multidrug‐resistant MDR1 protein, and other targets. Because of the number of new therapies clinical research in AML should emphasize pilot trials rather than traditionally large Phase III studies. CONCLUSIONS Most patients with newly diagnosed AML should be offered investigational regimens. Cancer 2001;92:1059–73. © 2001 American Cancer Society.

The evolving landscape in the therapy of acute myeloid leukemia

“…The prognosis of patients with t-MN is generally worse than for those with de novo AML, as it is more frequently impacted with high-risk cytogenetic and molecular features, rendering the disease more resistant to further therapies. Pre-existing myelodysplastic or myeloproliferative disorders are common in older patients who develop AML, occurring in 24%-40% of cases (Letendre et al, 1998;Estey, 2001;Wahlin et al, 2001;Bello et al, 2011). These pre-existing disorders are often associated with ineffective hematopoiesis and dysfunctional blood cells.…”

“…Several clinical and biologic characteristics help predict the likelihood of disease-free survival for patients with AML. Age, performance status, cytogenetic and molecular features, history of exposure to cytotoxic agents or radiation therapy, and history of prior myelodysplasia or other hematologic disorders all infl uence prognosis and risk, and thus direct postremission therapy (Estey, 2001;Sekeres et al, 2004;Olesen et al, 2005). In the majority of studies, advanced age (often defi ned as over age 60) correlates with lower rates of achieving complete remission and shorter disease-free survival, with a population characterized by stronger intrinsic resistance and lower tolerance to chemotherapy (Lowenberg et al, 1996;Leith et al, 1997;Lowenberg et al, 1998).…”

“…Patients >65 years had rates of 13%, 16%, 35%, and 60%, respectively. Another study found 28-day mortality to range from 5% for patients under the age of 50 years with an ECOG performance status <3 to 57% for patients over age 69 with an ECOG performance status of ≥3 (Estey, 2001). Those older patients with a worse performance status were also less likely to obtain a complete remission.…”

Leukemia targeting ligands isolated from phage display peptide libraries

“…Less than 40% of the patients diagnosed with AML younger than 60 years of age can be cured. [1][2][3][4] In older adults, who account for the majority of AML patients, the prognosis is much worse. Disease-free long-term survival is rare and the available treatment options are limited.…”

Cell-based selection of internalizing fully human antagonistic antibodies directed against FLT3 for suppression of leukemia cell growth

“…Following relapse of the disease, patients are usually treated with additional chemotherapies or stem cell transplantation. 1 This approach is marginally successful, with a 5-year survival rate of 30-40%, and less than 15% in elderly patients. 2 As with other cytotoxic therapies including radiation, these chemotherapeutic agents are usually nonspecific in their mechanisms of action; they often kill normal cells along with the cancer cells, leading to severe systemic toxicities.…”