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Prognostic Significance of Molecular Markers and Targeted Regimens in the Management of Acute Myeloid Leukemia

Martin Tallman

The diagnosis, staging, and treatment of acute myeloid leukemia (AML) has evolved based on identification of important genetic alterations and drugs to target those genes. Cytogenetic abnormalities play a major role in managing AML. Achieving minimal residual disease is an increasingly important milestone. Four new targeted therapies are now available for the treatment of AML.

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Growth Factors in Leukemia

Olga Frankfurt and Martin S. Tallman

The role of myeloid growth factors, such as granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor, in the management of acute myeloid and acute lymphoblastic leukemias has been evaluated extensively in multiple clinical trials. Growth factors have been given before, concurrently, or sequentially with chemotherapy with the goal of reducing the duration of neutropenia and consequently the incidence and severity of infections, and improving the rate of remissions and overall survival. They also have been studied as chemotherapy-sensitizing agents in an effort to recruit dormant myeloid stem cells into the sensitive phase of the cycle. Additionally, growth factors, shown to stimulate proliferation and differentiation of leukemia cells in vitro, were evaluated as monotherapy in patients with acute leukemia. Most studies show modest improvement in the duration of the neutropenia, which does not consistently correlate with the severity of infection, rate or duration of remissions, or disease-free and overall survival. Attempts to enhance the chemosensitivity of the leukemic cells and decrease drug resistance failed to improve the rate of remission and survival in several large series. However, more recent reports suggested an improved outcome in younger patients with acute myeloid leukemia with normal karyotype. Several anecdotal case reports have shown that growth factor monotherapy can induce a complete remission in patients with acute leukemia. Data from the published clinical trials do not seem to support emergence of drug-resistant leukemia, worsening toxicity, and bone marrow failure with growth factor administration.

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Strategies for the Treatment of Acute Promyelocytic Leukemia

Olga Frankfurt and Martin S. Tallman

The outcome of acute promyelocytic leukemia (APL) has improved dramatically during the past 40 years. Insights into the genetic and biologic mechanisms of APL lead to the development of specific and effective therapeutic strategies. This article discusses the therapeutic interventions that transformed APL from one of the most lethal leukemias to one that is highly curable.

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Postconsolidation Maintenance and Monitoring in Patients With Acute Promyelocytic Leukemia

Chezi Ganzel, Dan Douer, and Martin S. Tallman

Acute promyelocytic leukemia (APL) is a unique subtype of acute myeloid leukemia (AML). Its exclusivity is reflected by both the clinical course and the management of patients. This article discusses 2 aspects of the unique management of patients with APL: the role of maintenance therapy and polymerase chain reaction (PCR) monitoring. Despite common practice, the efficacy of maintenance therapy in APL is still debated, and the introduction of arsenic trioxide into frontline protocols makes this debate even more challenging. This article also attempts to clarify details regarding the type and duration of maintenance treatment. The presence of residual leukemic cells, seen using PCR analysis of the PML/RARα fusion gene product, in patients who have experienced a complete response has been shown to have a high correlation with subsequent relapse. This fact led to the broad use of PCR monitoring techniques in patients with APL. Practicing clinicians face several questions with regard to monitoring, such as what is the best technique for monitoring patients with APL, who can benefit the most from these tests, what are the best time points, and for how long is monitoring recommended. These questions are addressed in this article.

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Chronic Myelogenous Leukemia

Susan O'Brien, Ellin Berman, Hossein Borghaei, Daniel J. DeAngelo, Marcel P. Devetten, Steven Devine, Harry P. Erba, Jason Gotlib, Madan Jagasia, Joseph O. Moore, Tariq Mughal, Javier Pinilla-Ibarz, Jerald P. Radich, Neil P. Shah, Paul J. Shami, B. Douglas Smith, David S. Snyder, Martin S. Tallman, Moshe Talpaz, and Meir Wetzler

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Acute Myeloid Leukemia, Version 2.2013

Margaret R. O’Donnell, Martin S. Tallman, Camille N. Abboud, Jessica K. Altman, Frederick R. Appelbaum, Daniel A. Arber, Eyal Attar, Uma Borate, Steven E. Coutre, Lloyd E. Damon, Jeffrey Lancet, Lori J. Maness, Guido Marcucci, Michael G. Martin, Michael M. Millenson, Joseph O. Moore, Farhad Ravandi, Paul J. Shami, B. Douglas Smith, Richard M. Stone, Stephen A. Strickland, Eunice S. Wang, Kristina M. Gregory, and Maoko Naganuma

These NCCN Guidelines Insights summarize several key updates to the NCCN Guidelines for Acute Myeloid Leukemia and discuss the clinical evidence that support the recommendations. The updates described in this article focus on the acute promyelocytic leukemia (APL) section, featuring recommendations for additional induction/consolidation regimens in patients with low- or intermediate-risk APL, and providing guidance on maintenance strategies for APL.

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Acute Myeloid Leukemia

Margaret R. O'Donnell, Camille N. Abboud, Jessica Altman, Frederick R. Appelbaum, Daniel A. Arber, Eyal Attar, Uma Borate, Steven E. Coutre, Lloyd E. Damon, Salil Goorha, Jeffrey Lancet, Lori J. Maness, Guido Marcucci, Michael M. Millenson, Joseph O. Moore, Farhad Ravandi, Paul J. Shami, B. Douglas Smith, Richard M. Stone, Stephen A. Strickland, Martin S. Tallman, Eunice S. Wang, Maoko Naganuma, and Kristina M. Gregory

Acute myeloid leukemia (AML) remains the most common form of acute leukemia among adults and accounts for the largest number of annual deaths due to leukemias in the United States. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for AML provide recommendations on the diagnostic evaluation and workup for AML, risk assessment based on cytogenetic and molecular features, treatment options for induction and consolidation therapies for younger and older (age ≥ 65 years) adult patients, and key supportive care considerations.

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Myeloid Growth Factors

Jeffrey Crawford, James Armitage, Lodovico Balducci, Charles Bennett, Douglas W. Blayney, Spero R. Cataland, David C. Dale, George D. Demetri, Harry P. Erba, James Foran, Alison G. Freifeld, Marti Goemann, Mark L. Heaney, Sally Htoy, Susan Hudock, Dwight D. Kloth, David J. Kuter, Gary H. Lyman, Laura Boehnke Michaud, Sarah C. Miyata, Martin S. Tallman, Saroj Vadhan-Raj, Peter Westervelt, and Michael K. Wong

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Acute Myeloid Leukemia

Margaret R. O'Donnell, Camille N. Abboud, Jessica Altman, Frederick R. Appelbaum, Steven E. Coutre, Lloyd E. Damon, James M. Foran, Salil Goorha, Lori J. Maness, Guido Marcucci, Peter Maslak, Michael M. Millenson, Joseph O. Moore, Farhad Ravandi, Paul J. Shami, B. Douglas Smith, Richard M. Stone, Stephen A. Strickland, Martin S. Tallman, and Eunice S. Wang

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Acute Myeloid Leukemia, Version 3.2017, NCCN Clinical Practice Guidelines in Oncology

Margaret R. O'Donnell, Martin S. Tallman, Camille N. Abboud, Jessica K. Altman, Frederick R. Appelbaum, Daniel A. Arber, Vijaya Bhatt, Dale Bixby, William Blum, Steven E. Coutre, Marcos De Lima, Amir T. Fathi, Melanie Fiorella, James M. Foran, Steven D. Gore, Aric C. Hall, Patricia Kropf, Jeffrey Lancet, Lori J. Maness, Guido Marcucci, Michael G. Martin, Joseph O. Moore, Rebecca Olin, Deniz Peker, Daniel A. Pollyea, Keith Pratz, Farhad Ravandi, Paul J. Shami, Richard M. Stone, Stephen A. Strickland, Eunice S. Wang, Matthew Wieduwilt, Kristina Gregory, and Ndiya Ogba

Acute myeloid leukemia (AML) is the most common form of acute leukemia among adults and accounts for the largest number of annual deaths due to leukemias in the United States. This portion of the NCCN Guidelines for AML focuses on management and provides recommendations on the workup, diagnostic evaluation, and treatment options for younger (age <60 years) and older (age ≥60 years) adult patients.