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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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Jason Gotlib, Aaron T. Gerds, Prithviraj Bose, Mariana C. Castells, Michael W. Deininger, Ivana Gojo, Krishna Gundabolu, Gabriela Hobbs, Catriona Jamieson, Brandon McMahon, Sanjay R. Mohan, Vivian Oehler, Stephen Oh, Eric Padron, Philip Pancari, Nikolaos Papadantonakis, Animesh Pardanani, Nikolai Podoltsev, Raajit Rampal, Erik Ranheim, Lindsay Rein, David S. Snyder, Brady L. Stein, Moshe Talpaz, Swapna Thota, Martha Wadleigh, Katherine Walsh, Mary Anne Bergman and Hema Sundar

Mastocytosis is a group of heterogeneous disorders resulting from the clonal proliferation of abnormal mast cells and their accumulation in the skin and/or in various extracutaneous organs. Systemic mastocytosis is the most common form of mastocytosis diagnosed in adults, characterized by mast cell infiltration of one or more extracutaneous organs (with or without skin involvement). The identification of KIT D816V mutation and the emergence of novel targeted therapies have significantly improved the diagnosis and treatment of systemic mastocytosis. However, certain aspects of clinical care, particularly the diagnosis, assessment, and management of mediator-related symptoms continue to present challenges. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with systemic mastocytosis.

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Ruben Mesa, Catriona Jamieson, Ravi Bhatia, Michael W. Deininger, Aaron T. Gerds, Ivana Gojo, Jason Gotlib, Krishna Gundabolu, Gabriela Hobbs, Rebecca B. Klisovic, Patricia Kropf, Sanjay R. Mohan, Stephen Oh, Eric Padron, Nikolai Podoltsev, Daniel A. Pollyea, Raajit Rampal, Lindsay A. M. Rein, Bart Scott, David S. Snyder, Brady L. Stein, Srdan Verstovsek, Martha Wadleigh, Eunice S. Wang, Mary Anne Bergman, Kristina M. Gregory and Hema Sundar

Myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET) are a group of heterogeneous disorders of the hematopoietic system collectively known as Philadelphia chromosome–negative myeloproliferative neoplasms (MPNs). The diagnosis and the management of patients with MPNs have evolved since the identification of mutations that activate the JAK pathway (JAK2, CALR, and MPL mutations) and the development of targeted therapies has resulted in significant improvements in disease-related symptoms and quality of life. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnostic workup of MPN (MF, PV, and ET), risk stratification, treatment, and supportive care strategies for the management of MF.

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Elizabeth A. Griffiths, Laura M. Alwan, Kimo Bachiashvili, Anna Brown, Rita Cool, Peter Curtin, Mark B. Geyer, Ivana Gojo, Avyakta Kallam, Wajih Z. Kidwai, Dwight D. Kloth, Eric H. Kraut, Gary H. Lyman, Sudipto Mukherjee, Lia E. Perez, Rachel P. Rosovsky, Vivek Roy, Hope S. Rugo, Sumithira Vasu, Martha Wadleigh, Peter Westervelt and Pamela S. Becker

Hematopoietic growth factors, including erythrocyte stimulating agents (ESAs), granulocyte colony-stimulating factors, and thrombopoietin mimetics, can mitigate anemia, neutropenia, and thrombocytopenia resulting from chemotherapy for the treatment of cancer. In the context of pandemic SARS-CoV-2 infection, patients with cancer have been identified as a group at high risk of morbidity and mortality from this infection. Our subcommittee of the NCCN Hematopoietic Growth Factors Panel convened a voluntary group to review the potential value of expanded use of such growth factors in the current high-risk environment. Although recommendations are available on the NCCN website in the COVID-19 Resources Section (https://www.nccn.org/covid-19/), these suggestions are provided without substantial context or reference. Herein we review the rationale and data underlying the suggested alterations to the use of hematopoietic growth factors for patients with cancer in the COVID-19 era.

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Brady L. Stein, Jason Gotlib, Murat Arcasoy, Marie Huong Nguyen, Neil Shah, Alison Moliterno, Catriona Jamieson, Daniel A. Pollyea, Bart Scott, Martha Wadleigh, Ross Levine, Rami Komrokji, Rebecca Klisovic, Krishna Gundabolu, Patricia Kropf, Meir Wetzler, Stephen T. Oh, Raul Ribeiro, Rita Paschal, Sanjay Mohan, Nikolai Podoltsev, Josef Prchal, Moshe Talpaz, David Snyder, Srdan Verstovsek and Ruben A. Mesa

The classical Philadelphia chromosome–negative myeloproliferative neoplasms (MPN), which include essential thrombocythemia, polycythemia vera, and myelofibrosis (MF), are in a new era of molecular diagnosis, ushered in by the identification of the JAK2 V617F and cMPL mutations in 2005 and 2006, respectively, and the CALR mutations in 2013. Coupled with increased knowledge of disease pathogenesis and refined diagnostic criteria and prognostic scoring systems, a more nuanced appreciation has emerged of the burden of MPN in the United States, including the prevalence, symptom burden, and impact on quality of life. Biological advances in MPN have translated into the rapid development of novel therapeutics, culminating in the approval of the first treatment for MF, the JAK1/JAK2 inhibitor ruxolitinib. However, certain practical aspects of care, such as those regarding diagnosis, prevention of vascular events, choice of cytoreductive agent, and planning for therapies, present challenges for hematologists/oncologists, and are discussed in this article.

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Jeffrey Crawford, Pamela Sue Becker, James O. Armitage, Douglas W. Blayney, Julio Chavez, Peter Curtin, Shira Dinner, Thomas Fynan, Ivana Gojo, Elizabeth A. Griffiths, Shannon Hough, Dwight D. Kloth, David J. Kuter, Gary H. Lyman, Mary Mably, Sudipto Mukherjee, Shiven Patel, Lia E. Perez, Adam Poust, Raajit Rampal, Vivek Roy, Hope S. Rugo, Ayman A. Saad, Lee S. Schwartzberg, Sepideh Shayani, Mahsa Talbott, Saroj Vadhan-Raj, Sumithira Vasu, Martha Wadleigh, Peter Westervelt, Jennifer L. Burns and Lenora Pluchino

Myeloid growth factors (MGFs) are given as supportive care to patients receiving myelosuppressive chemotherapy to reduce the incidence of neutropenia. This selection from the NCCN Guidelines for MGFs focuses on the evaluation of regimen- and patient-specific risk factors for the development of febrile neutropenia (FN), the prophylactic use of MGFs for the prevention of chemotherapy-induced FN, and assessing the risks and benefits of MGF use in clinical practice.

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Ruben A. Mesa, Catriona Jamieson, Ravi Bhatia, Michael W. Deininger, Christopher D. Fletcher, Aaron T. Gerds, Ivana Gojo, Jason Gotlib, Krishna Gundabolu, Gabriela Hobbs, Brandon McMahon, Sanjay R. Mohan, Stephen Oh, Eric Padron, Nikolaos Papadantonakis, Philip Pancari, Nikolai Podoltsev, Raajit Rampal, Erik Ranheim, Vishnu Reddy, Lindsay A.M. Rein, Bart Scott, David S. Snyder, Brady L. Stein, Moshe Talpaz, Srdan Verstovsek, Martha Wadleigh, Eunice S. Wang, Mary Anne Bergman, Kristina M. Gregory and Hema Sundar

Myeloproliferative neoplasms (MPNs) are a group of heterogeneous disorders of the hematopoietic system that include myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET). PV and ET are characterized by significant thrombohemorrhagic complications and a high risk of transformation to MF and acute myeloid leukemia. The diagnosis and management of PV and ET has evolved since the identification of mutations implicated in their pathogenesis. These NCCN Guideline Insights discuss the recommendations outlined in the NCCN Guidelines for the risk stratification, treatment, and special considerations for the management of PV and ET.

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Pamela Sue Becker, Elizabeth A. Griffiths, Laura M. Alwan, Kimo Bachiashvili, Anna Brown, Rita Cool, Peter Curtin, Shira Dinner, Ivana Gojo, Ashley Hicks, Avyakta Kallam, Wajih Zaheer Kidwai, Dwight D. Kloth, Eric H. Kraut, Daniel Landsburg, Gary H. Lyman, Ryan Miller, Sudipto Mukherjee, Shiven Patel, Lia E. Perez, Adam Poust, Raajit Rampal, Rachel Rosovsky, Vivek Roy, Hope S. Rugo, Sepideh Shayani, Sumithira Vasu, Martha Wadleigh, Kelly Westbrook, Peter Westervelt, Jennifer Burns, Jennifer Keller and Lenora A. Pluchino

Management of febrile neutropenia (FN) is an integral part of supportive care for patients undergoing cancer treatment. The NCCN Guidelines for Hematopoietic Growth Factors provide suggestions for appropriate evaluation, risk determination, prophylaxis, and management of FN. These NCCN Guidelines are intended to guide clinicians in the appropriate use of growth factors for select patients undergoing treatment of nonmyeloid malignancies. These NCCN Guidelines Insights highlight important updates to the NCCN Guidelines regarding the incorporation of newly FDA-approved granulocyte-colony stimulating factor biosimilars for the prevention and treatment of FN.

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Aaron T. Gerds, Jason Gotlib, Prithviraj Bose, Michael W. Deininger, Andrew Dunbar, Amro Elshoury, Tracy I. George, Ivana Gojo, Krishna Gundabolu, Elizabeth Hexner, Gabriela Hobbs, Tania Jain, Catriona Jamieson, Andrew T. Kuykendall, Brandon McMahon, Sanjay R. Mohan, Vivian Oehler, Stephen Oh, Animesh Pardanani, Nikolai Podoltsev, Erik Ranheim, Lindsay Rein, Rachel Salit, David S. Snyder, Brady L. Stein, Moshe Talpaz, Swapna Thota, Pankit Vachhani, Martha Wadleigh, Katherine Walsh, Dawn C. Ward, Mary Anne Bergman and Hema Sundar

Eosinophilic disorders and related syndromes represent a heterogeneous group of neoplastic and nonneoplastic conditions, characterized by more eosinophils in the peripheral blood, and may involve eosinophil-induced organ damage. In the WHO classification of myeloid and lymphoid neoplasms, eosinophilic disorders characterized by dysregulated tyrosine kinase (TK) fusion genes are recognized as a new category termed, myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB or FGFR1 or with PCM1-JAK2. In addition to these aforementioned TK fusion genes, rearrangements involving FLT3 and ABL1 genes have also been described. These new NCCN Guidelines include recommendations for the diagnosis, staging, and treatment of any one of the myeloid/lymphoid neoplasms with eosinophilia (MLN-Eo) and a TK fusion gene included in the 2017 WHO Classification, as well as MLN-Eo and a FLT3 or ABL1 rearrangement.