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The Role of Myeloid Growth Factors in Acute Leukemia

Martha Wadleigh and Richard M. Stone

Myeloid growth factors granulocyte-colony stimulating and granulocyte macrophage colony-stimulating factors have been extensively studied in acute leukemias. Whether administered before, during, or after chemotherapy for acute myeloid leukemia and acute lymphoblastic leukemia, these agents reduce the duration of neutropenia and seem to be safe and well tolerated. Despite consistently showing a shorter duration of neutropenia, multiple, prospective, randomized trials have documented only modest benefits in terms of reduction in the incidence and severity of infections, without substantial gains or impact in complete remission, overall survival, and disease-free survival rates. Growth factors have also been used to recruit quiescent leukemia cells into the S-phase of the cell cycle to increase their susceptibility to chemotherapy with the goal to reduce relapse and resistance. Randomized trials evaluating this priming strategy have consistently shown improvement in disease- or event-free survival in the intermediate-risk group of patients with acute myeloid leukemia, but no overall survival benefit. This article focuses on the clinical experience with these agents as adjuncts to the treatment of acute leukemias.

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NCCN Task Force: Transfusion and Iron Overload in Patients With Myelodysplastic Syndromes

Peter L. Greenberg, Cynthia K. Rigsby, Richard M. Stone, H. Joachim Deeg, Steven D. Gore, Michael M. Millenson, Stephen D. Nimer, Margaret R. O'Donnell, Paul J. Shami, and Rashmi Kumar

The National Comprehensive Cancer Network (NCCN) convened a multidisciplinary task force to critically review the evidence for iron chelation and the rationale for treatment of transfusional iron overload in patients with myelodysplastic syndromes (MDS). The task force was charged with addressing issues related to tissue iron toxicity; the role of MRI in assessing iron overload; the rationale and role of treating transfusional iron overload in patients with MDS; and the impact of iron overload on bone marrow transplantation. This report summarizes the background data and ensuing discussion from the NCCN Task Force meeting on transfusional iron overload in MDS.

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Association of Polypharmacy and Potentially Inappropriate Medications With Frailty Among Older Adults With Blood Cancers

Tammy T. Hshieh, Clark DuMontier, Timothy Jaung, Nupur E. Bahl, Chelsea E. Hawley, Lee Mozessohn, Richard M. Stone, Robert J. Soiffer, Jane A. Driver, and Gregory A. Abel

Background: Polypharmacy and potentially inappropriate medications (PIMs) are common among older adults with blood cancers, but their association with frailty and how to manage them optimally remain unclear. Patients and Methods: From 2015 to 2019, patients aged ≥75 years presenting for initial oncology consult underwent screening geriatric assessment. Patients were determined to be robust, prefrail, or frail via deficit accumulation and phenotypic approaches. We quantified each patient’s total number of medications and PIMs using the Anticholinergic Risk Scale (ARS) and a scale we generated using the NCCN Medications of Concern called the Geriatric Oncology Potentially Inappropriate Medications (GO-PIM) scale. We assessed cross-sectional associations of PIMs with frailty in multivariable regression models adjusting for age, gender, and comorbidity. Results: Of 785 patients assessed, 603 (77%) were taking ≥5 medications and 421 (54%) were taking ≥8 medications; 201 (25%) were taking at least 1 PIM based on the ARS and 343 (44%) at least 1 PIM based on the GO-PIM scale. Among the 468 (60%) patients on active cancer treatment, taking ≥8 medications was associated with frailty (adjusted odds ratio [aOR], 2.82; 95% CI, 1.92–4.17). With each additional medication, the odds of being prefrail or frail increased 8% (aOR, 1.08; 95% CI, 1.04–1.12). With each 1-point increase on the ARS, the odds of being prefrail or frail increased 19% (aOR, 1.19; 95% CI, 1.03–1.39); with each additional PIM based on the GO-PIM scale, the odds increased 65% (aOR, 1.65; 95% CI, 1.34–2.04). Conclusions: Polypharmacy and PIMs are prevalent among older patients with blood cancers; taking ≥8 medications is strongly associated with frailty. These data suggest careful medication reconciliation for this population may be helpful, and deprescribing when possible is high-yield, especially for PIMs on the GO-PIM scale.

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Myelodysplastic Syndromes

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

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Myelodysplastic Syndromes

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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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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Myelodysplastic Syndromes, Version 2.2015

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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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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Myelodysplastic Syndromes, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology

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.