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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

OverviewIn 2010, approximately 12,330 people were diagnosed with and 8950 died of acute myeloid leukemia (AML).1 As the population ages, the incidence of AML, along with myelodysplasia, seems to be rising. Equally disturbing is the increasing incidence of treatment-related myelodysplasia and leukemia in survivors of childhood tumors and young adulthood, such as Hodgkin disease, sarcomas, breast and testicular cancers, and lymphomas. Ionizing radiation and occupational exposure to benzene and petrochemicals are also associated with AML.2The NCCN AML Panel convenes annually to update guidelines for the diagnosis and treatment of AML in adults. Clinical trials have led to significant improvements in treatment in some areas, primarily in acute promyelocytic leukemia (APL). However, recent large clinical trials have highlighted the need for new, innovative strategies because outcomes for patients, particularly older patients, have not substantially changed in the past 3 decades.The panel has focused on outlining reasonable treatment options based on recent clinical trials and data from basic science, which may identify new risk factors and treatment approaches. In some areas, panel members have divergent opinions about the relative risks and benefits of various treatment options. Therefore, these guidelines attempt to provide a rationale for the inclusion of several treatment options in some categories.Initial EvaluationInitial evaluation has 2 objectives. The first is to characterize the disease process, including factors such as 1) prior toxic exposure, 2) myelodysplasia, and 3) karyotypic or molecular abnormalities, which may provide prognostic information that could influence responsiveness to chemotherapy and risk of...
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Peter L. Greenberg, Eyal Attar, John M. Bennett, Clara D. Bloomfield, Carlos M. De Castro, H. Joachim Deeg, James M. Foran, Karin Gaensler, Guillermo Garcia-Manero, Steven D. Gore, David Head, Rami Komrokji, Lori J. Maness, Michael Millenson, Stephen D. Nimer, Margaret R. O'Donnell, Mark A. Schroeder, Paul J. Shami, Richard M. Stone, James E. Thompson and Peter Westervelt

Overview The myelodysplastic syndromes (MDS) represent myeloid clonal hemopathies with relatively heterogeneous spectrums of presentation. The major clinical problems in these disorders are morbidities caused by cytopenias and the potential for MDS to evolve into acute myeloid leukemia (AML). In the general population, MDS occur in 5 per 100,000 people. However, among individuals older than 70 years, the incidence increases to between 22 and 45 per 100,000 and increases further with age. Managing MDS is complicated by the generally advanced age of the patients (median ages, 65–70 years), attendant nonhematologic comorbidities, and relative inability to tolerate certain intensive forms of therapy among older patients. In addition, when the illness progresses to AML, these patients experience lower response rates to standard therapy than those with de novo AML.1 Diagnostic Classification Initial evaluation of patients with suspected MDS requires careful assessment of their peripheral blood smear and blood counts, marrow morphology, duration of their abnormal blood counts, other potential causes for their cytopenias, and concomitant illnesses. The French-American-British (FAB) classification initially categorized patients for the diagnostic evaluation of MDS.2 Dysplastic changes in at least 2 of the 3 hematopoietic cell lines have been used by most histopathologists to diagnose MDS. These changes include megaloblastoid erythropoiesis, nucleocytoplasmic asynchrony in the early myeloid and erythroid precursors, and dysmorphic megakaryocytes.3 Patients with MDS are classified as having 1 of 5 subtypes of disease: refractory anemia (RA); RA with ringed sideroblasts (RARS); RA with excess of blasts (RAEB); RAEB in transformation (RAEB-T); or chronic myelomonocytic leukemia...
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Peter L. Greenberg, Eyal Attar, John M. Bennett, Clara D. Bloomfield, Uma Borate, Carlos M. De Castro, H. Joachim Deeg, Olga Frankfurt, Karin Gaensler, Guillermo Garcia-Manero, Steven D. Gore, David Head, Rami Komrokji, Lori J. Maness, Michael Millenson, Margaret R. O’Donnell, Paul J. Shami, Brady L. Stein, Richard M. Stone, James E. Thompson, Peter Westervelt, Benton Wheeler, Dorothy A. Shead and Maoko Naganuma

The myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal hematopoietic disorders characterized by cytopenias, dysplasia in one or more myeloid lineages, and the potential for development of acute myeloid leukemia. These disorders primarily affect older adults. The NCCN Clinical Practice Guidelines in Oncology for MDS provide recommendations on the diagnostic evaluation and classification of MDS, risk evaluation according to established prognostic assessment tools (including the new revised International Prognostic Scoring System), treatment options according to risk categories, and management of related anemia.

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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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Jerald P. Radich, Michael Deininger, Camille N. Abboud, Jessica K. Altman, Ellin Berman, Ravi Bhatia, Bhavana Bhatnagar, Peter Curtin, Daniel J. DeAngelo, Jason Gotlib, Gabriela Hobbs, Madan Jagasia, Hagop M. Kantarjian, Lori Maness, Leland Metheny, Joseph O. Moore, Arnel Pallera, Philip Pancari, Mrinal Patnaik, Enkhtsetseg Purev, Michal G. Rose, Neil P. Shah, B. Douglas Smith, David S. Snyder, Kendra L. Sweet, Moshe Talpaz, James Thompson, David T. Yang, Kristina M. Gregory and Hema Sundar

Chronic myeloid leukemia (CML) is defined by the presence of Philadelphia chromosome (Ph), resulting from a reciprocal translocation between chromosomes 9 and 22 [t(9;22] that gives rise to a BCR-ABL1 fusion gene. CML occurs in 3 different phases (chronic, accelerated, and blast phase) and is usually diagnosed in the chronic phase. Tyrosine kinase inhibitor (TKI) therapy is a highly effective first-line treatment option for all patients with newly diagnosed chronic phase CML (CP-CML). The selection TKI therapy should be based on the risk score, toxicity profile of TKI, patient's age, ability to tolerate therapy, and the presence of comorbid conditions. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with CP-CML.

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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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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.

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Peter L. Greenberg, Richard M. Stone, Rafael Bejar, John M. Bennett, Clara D. Bloomfield, Uma Borate, Carlos M. De Castro, H. Joachim Deeg, Amy E. DeZern, Amir T. Fathi, Olga Frankfurt, Karin Gaensler, Guillermo Garcia-Manero, Elizabeth A. Griffiths, David Head, Virginia Klimek, Rami Komrokji, Lisa A. Kujawski, Lori J. Maness, Margaret R. O’Donnell, Daniel A. Pollyea, Bart Scott, Paul J. Shami, Brady L. Stein, Peter Westervelt, Benton Wheeler, Dorothy A. Shead and Courtney Smith

The NCCN Guidelines for Myelodysplastic Syndromes (MDS) comprise a heterogeneous group of myeloid disorders with a highly variable disease course that depends largely on risk factors. Risk evaluation is therefore a critical component of decision-making in the treatment of MDS. The development of newer treatments and the refinement of current treatment modalities are designed to improve patient outcomes and reduce side effects. These NCCN Guidelines Insights focus on the recent updates to the guidelines, which include the incorporation of a revised prognostic scoring system, addition of molecular abnormalities associated with MDS, and refinement of treatment options involving a discussion of cost of care.

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Peter L. Greenberg, Richard M. Stone, Aref Al-Kali, Stefan K. Barta, Rafael Bejar, John M. Bennett, Hetty Carraway, Carlos M. De Castro, H. Joachim Deeg, Amy E. DeZern, Amir T. Fathi, Olga Frankfurt, Karin Gaensler, Guillermo Garcia-Manero, Elizabeth A. Griffiths, David Head, Ruth Horsfall, Robert A. Johnson, Mark Juckett, Virginia M. Klimek, Rami Komrokji, Lisa A. Kujawski, Lori J. Maness, Margaret R. O'Donnell, Daniel A. Pollyea, Paul J. Shami, Brady L. Stein, Alison R. Walker, Peter Westervelt, Amer Zeidan, Dorothy A. Shead and Courtney Smith

The myelodysplastic syndromes (MDS) comprise a heterogenous group of myeloid disorders with a highly variable disease course. Diagnostic criteria to better stratify patients with MDS continue to evolve, based on morphology, cytogenetics, and the presence of cytopenias. More accurate classification of patients will allow for better treatment guidance. Treatment encompasses supportive care, treatment of anemia, low-intensity therapy, and high-intensity therapy. This portion of the guidelines focuses on diagnostic classification, molecular abnormalities, therapeutic options, and recommended treatment approaches.