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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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Cancer- and Chemotherapy-Induced Anemia

George M. Rodgers III, Pamela Sue Becker, Morey Blinder, David Cella, Asher Chanan-Khan, Charles Cleeland, Peter F. Coccia, Benjamin Djulbegovic, Jeffrey A. Gilreath, Eric H. Kraut, Ursula A. Matulonis, Michael M. Millenson, Denise Reinke, Joseph Rosenthal, Rowena N. Schwartz, Gerald Soff, Richard S. Stein, Gordana Vlahovic, and Alva B. Weir III

Anemia is prevalent in 30% to 90% of patients with cancer. Anemia can be corrected through either treating the underlying cause or providing supportive care through transfusion with packed red blood cells or administration of erythropoiesis-stimulating agents (ESAs), with or without iron supplementation. Recent studies showing detrimental health effects of ESAs sparked a series of FDA label revisions and a sea change in the perception of these once commonly used agents. In light of this, the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cancer- and Chemotherapy-Induced Anemia underwent substantial revisions this year. The purpose of these NCCN Guidelines is twofold: 1) to operationalize the evaluation and treatment of anemia in adult cancer patients, with an emphasis on those who are receiving concomitant chemotherapy, and 2) to enable patients and clinicians to individualize anemia treatment options based on patient condition.

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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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High Body Mass Index in Elderly Patients With DLBCL Treated With Rituximab-Containing Therapy Compensates for Negative Impact of Male Sex

Zheng Zhou, Alfred W. Rademaker, Leo I. Gordon, Ann S. LaCasce, Allison Crosby-Thompson, Ann Vanderplas, Gregory A. Abel, Maria A. Rodriguez, Auayporn Nademanee, Mark S. Kaminski, Myron S. Czuczman, Michael M. Millenson, Andrew D. Zelenetz, Joyce Niland, Jonathan W. Friedberg, and Jane N. Winter

Background: The impact of patient body habitus and sex on outcomes in diffuse large B-cell lymphoma (DLBCL) remains controversial. We investigated the impact of body mass index (BMI), body surface area (BSA), age, and sex on clinical outcomes in patients with DLBCL treated in the rituximab era. Patients and Methods: Patients with de novo DLBCL (n=1,386) diagnosed between June 2000 and December 2010 treated with rituximab-containing chemotherapy were identified from the NCCN Oncology Outcomes Database for Non-Hodgkin's Lymphoma. Progression-free survival (PFS) and overall survival (OS) at 3 years were analyzed based on sex, age, and baseline BMI/BSA. Results: High BMI was associated with a lower risk of disease progression or death than low or normal BMI, whereas male sex was associated with poor clinical outcomes, especially among elderly patients (age >60 years). Compared with elderly women, elderly men experienced worse PFS (3-year hazard ratio [HR], 1.5) and OS (3-year HR, 1.6), but these differences diminished with increases in BMI and BSA. In multivariable analysis, normal BMI compared with high BMI was independently associated with poor outcomes (3-year PFS HR, 1.5; OS HR, 1.6) after adjusting for sex. Notably, only 13% of elderly men had BMI less than 25 kg/m2 and only 26% had BSA less than 2 m2. Conclusions: Analysis of unselected patients with DLBCL treated with rituximab-containing chemotherapy confirmed an age-dependent disadvantage to male sex in treatment outcomes, but this effect is abrogated by higher levels of BMI and BSA in most North American men.

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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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Acute Lymphoblastic Leukemia

Joseph C. Alvarnas, Patrick A. Brown, Patricia Aoun, Karen Kuhn Ballen, Naresh Bellam, William Blum, Michael W. Boyer, Hetty E. Carraway, Peter F. Coccia, Steven E. Coutre, Jennifer Cultrera, Lloyd E. Damon, Daniel J. DeAngelo, Dan Douer, Haydar Frangoul, Olga Frankfurt, Salil Goorha, Michael M. Millenson, Susan O'Brien, Stephen H. Petersdorf, Arati V. Rao, Stephanie Terezakis, Geoffrey Uy, Meir Wetzler, Andrew D. Zelenetz, Maoko Naganuma, and Kristina M. Gregory

The inaugural NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for acute lymphoblastic leukemia (ALL) were developed as a result of meetings convened by a multi-disciplinary panel of experts in 2011. These NCCN Guidelines provide recommendations on the diagnostic evaluation and workup for ALL, risk assessment, risk-stratified treatment approaches based on the Philadelphia chromosome status and age (adults vs. adolescents/young adults), assessment of minimal residual disease, and supportive care considerations. It is recommended that patients be treated at specialized centers with expertise in the management of ALL.

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Cancer-Associated Venous Thromboembolic Disease, Version 1.2015

Michael B. Streiff, Bjorn Holmstrom, Aneel Ashrani, Paula L. Bockenstedt, Carolyn Chesney, Charles Eby, John Fanikos, Randolph B. Fenninger, Annemarie E. Fogerty, Shuwei Gao, Samuel Z. Goldhaber, Paul Hendrie, Nicole Kuderer, Alfred Lee, Jason T. Lee, Mirjana Lovrincevic, Michael M. Millenson, Anne T. Neff, Thomas L. Ortel, Rita Paschal, Sanford Shattil, Tanya Siddiqi, Kristi J. Smock, Gerald Soff, Tzu-Fei Wang, Gary C. Yee, Anaadriana Zakarija, Nicole McMillian, and Anita M. Engh

The NCCN Guidelines for Cancer-Associated Venous Thromboembolic Disease outline strategies for treatment and prevention of venous thromboembolism (VTE) in adult patients with a diagnosis of cancer or for whom cancer is clinically suspected. VTE is a common complication in patients with cancer, which places them at greater risk for morbidity and mortality. Therefore, risk-appropriate prophylaxis is an essential component for the optimal care of inpatients and outpatients with cancer. Critical to meeting this goal is ensuring that patients get the most effective medication in the correct dose. Body weight has a significant impact on blood volume and drug clearance. Because obesity is a common health problem in industrialized societies, cancer care providers are increasingly likely to treat obese patients in their practice. Obesity is a risk factor common to VTE and many cancers, and may also impact the anticoagulant dose needed for safe and effective prophylaxis. These NCCN Guidelines Insights summarize the data supporting new dosing recommendations for VTE prophylaxis in obese patients with cancer.

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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

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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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