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John C. Byrd

In the treatment of chronic lymphocytic leukemia (CLL), select genomic studies can assist in risk stratification of newly diagnosed patients. Chemoimmunotherapy targeting CD20 offers a survival advantage in symptomatic patients both with and without these high-risk genetic features, though patients with del(17p13.1) have poor outcomes and require specific intervention. Obinutuzumab plus chlorambucil is a treatment standard for untreated elderly patients and is superior to rituximab plus chlorambucil. In the setting of relapsed CLL, the new kinase inhibitors have the potential to completely change the treatment paradigm of CLL.

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Sandipkumar H. Patel, Sumithira Vasu, Ling Guo, Olivia Lemaster, John C. Byrd and Alison Walker

Acute undifferentiated leukemia (AUL) is a subtype of acute leukemias of ambiguous lineage. There is no standard treatment approach for AUL, although acute lymphoblastic leukemia–like regimens for induction therapy have been used. Additional data suggest that AUL may be better treated as acute myeloid leukemia (AML), given their similarities in genetic, cytogenetic, and gene expression patterns. Somatic mutations of IDH1 are found in 7% to 14% of patients with AML; however, the patient in this study was the first patient with IDH1-mutated AUL treated with ivosidenib. In this case, a woman aged 39 years was found to have anemia and thrombocytopenia after presenting to her primary care physician with fatigue, weight loss, and persistent infections. During further workup of the cytopenia, she was diagnosed with AUL and received 7+3 (daunorubicin, 60 mg/m2/d intravenously on days 1–3, and cytarabine, 100 mg/m2 24-hour continuous intravenous infusion on days 1–7) due to the presence of the IDH1 mutation. Bone marrow biopsy performed on day 14 of 7+3 showed persistent disease, and ivosidenib was initiated due to severe HLA alloimmunization (panel-reactive antibody, 100%) and significant bleeding complications. The patient achieved a complete morphologic and molecular remission on ivosidenib monotherapy despite critical bleeding complications during induction. Targeted therapy using ivosidenib may represent an encouraging therapeutic option in patients with AUL and IDH1 mutations. Additional evaluation of ivosidenib in this subgroup of patients with AUL is needed.

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R. Michael Tuttle, Douglas W. Ball, David Byrd, Raza A. Dilawari, Gerard M. Doherty, Quan-Yang Duh, Hormoz Ehya, William B. Farrar, Robert I. Haddad, Fouad Kandeel, Richard T. Kloos, Peter Kopp, Dominick M. Lamonica, Thom R. Loree, William M. Lydiatt, Judith C. McCaffrey, John A. Olson Jr., Lee Parks, John A. Ridge, Jatin P. Shah, Steven I. Sherman, Cord Sturgeon, Steven G. Waguespack, Thomas N. Wang and Lori J. Wirth

Overview Epidemiology Thyroid nodules are approximately 4 times more common in women than in men. Palpable nodules increase in frequency throughout life, reaching a prevalence of approximately 5% in the United States population aged 50 years and older.1–3 Nodules are even more prevalent when the thyroid gland is examined at autopsy or surgery, or when using ultrasonography, and 50% of these have nodules, which are almost always benign.2,4 New nodules develop at a rate of approximately 0.1% per year beginning in early life, but at a much higher rate (∼2% per year) after exposure to head and neck irradiation.5,6 By contrast, thyroid carcinoma is uncommon. For the United States population, the lifetime risk of being diagnosed with thyroid carcinoma is less than 1% (0.83% for women and 0.33% for men).7 Approximately 37,200 new cases of thyroid carcinoma were diagnosed in the United States in 2009.8 As with thyroid nodules, thyroid carcinoma occurs 2 to 3 times more often in women than in men. With the incidence increasing by 6.2% per year, thyroid carcinoma is currently the sixth most common malignancy diagnosed in women.8 Among persons age 15 to 24 years, thyroid carcinoma accounts for 7.5% to 10% of all diagnosed malignancies.9–11 The disease is also diagnosed more often in white North Americans than in African Americans. Although thyroid carcinoma can occur at any age, the peak incidence from 2004 to 2006 was near age 45 to 49 years in women and 65 to 69 years in men.7 Thyroid carcinoma has...
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Robert I. Haddad, William M. Lydiatt, Douglas W. Ball, Naifa Lamki Busaidy, David Byrd, Glenda Callender, Paxton Dickson, Quan-Yang Duh, Hormoz Ehya, Megan Haymart, Carl Hoh, Jason P. Hunt, Andrei Iagaru, Fouad Kandeel, Peter Kopp, Dominick M. Lamonica, Judith C. McCaffrey, Jeffrey F. Moley, Lee Parks, Christopher D. Raeburn, John A. Ridge, Matthew D. Ringel, Randall P. Scheri, Jatin P. Shah, Robert C. Smallridge, Cord Sturgeon, Thomas N. Wang, Lori J. Wirth, Karin G. Hoffmann and Miranda Hughes

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Thyroid Carcinoma focuses on anaplastic carcinoma because substantial changes were made to the systemic therapy recommendations for the 2015 update. Dosages and frequency of administration are now provided, docetaxel/doxorubicin regimens were added, and single-agent cisplatin was deleted because it is not recommended for patients with advanced or metastatic anaplastic thyroid cancer.

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William G. Wierda, John C. Byrd, Jeremy S. Abramson, Seema Bhat, Greg Bociek, Danielle Brander, Jennifer Brown, Asher Chanan-Khan, Steve E. Coutre, Randall S. Davis, Christopher D. Fletcher, Brian Hill, Brad S. Kahl, Manali Kamdar, Lawrence D. Kaplan, Nadia Khan, Thomas J. Kipps, Jeffrey Lancet, Shuo Ma, Sami Malek, Claudio Mosse, Mazyar Shadman, Tanya Siddiqi, Deborah Stephens, Nina Wagner, Andrew D. Zelenetz, Mary A. Dwyer and Hema Sundar

Hairy cell leukemia (HCL) is a rare type of indolent B-cell leukemia, characterized by symptoms of fatigue and weakness, organomegaly, pancytopenia, and recurrent opportunistic infections. Classic HCL should be considered a distinct clinical entity separate from HCLvariant (HCLv), which is associated with a more aggressive disease course and may not respond to standard HCL therapies. Somatic hypermutation in the IGHV gene is present in most patients with HCL. The BRAF V600E mutation has been reported in most patients with classic HCL but not in those with other B-cell leukemias or lymphomas. Therefore, it is necessary to distinguish HCLv from classic HCL. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of classic HCL.

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Andrew D. Zelenetz, William G. Wierda, Jeremy S. Abramson, Ranjana H. Advani, C. Babis Andreadis, Nancy Bartlett, Naresh Bellam, John C. Byrd, Myron S. Czuczman, Luis E. Fayad, Martha J. Glenn, Jon P. Gockerman, Leo I. Gordon, Nancy Lee Harris, Richard T. Hoppe, Steven M. Horwitz, Christopher R. Kelsey, Youn H. Kim, Susan Krivacic, Ann S. LaCasce, Auayporn Nademanee, Pierluigi Porcu, Oliver Press, Barbara Pro, Nishitha Reddy, Lubomir Sokol, Lode Swinnen, Christina Tsien, Julie M. Vose, Joachim Yahalom, Nadeem Zafar, Mary A. Dwyer and Maoko Naganuma

These NCCN Guidelines Insights summarize several key updates to the NCCN Guidelines for Non-Hodgkin’s Lymphomas (NHL) and provide a discussion of the clinical evidence that support the updates. The updates discussed in this article feature recommendations for additional treatment options in patients with chronic lymphocytic leukemia and guidance surrounding the management of hepatitis virus reactivation/infections in high-risk patients with NHL undergoing antitumor therapy.

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Andrew D. Zelenetz, Leo I. Gordon, William G. Wierda, Jeremy S. Abramson, Ranjana H. Advani, C. Babis Andreadis, Nancy Bartlett, John C. Byrd, Myron S. Czuczman, Luis E. Fayad, Richard I. Fisher, Martha J. Glenn, Nancy Lee Harris, Richard T. Hoppe, Steven M. Horwitz, Christopher R. Kelsey, Youn H. Kim, Susan Krivacic, Ann S. LaCasce, Auayporn Nademanee, Pierluigi Porcu, Oliver Press, Rachel Rabinovitch, Nishitha Reddy, Erin Reid, Ayman A. Saad, Lubomir Sokol, Lode J. Swinnen, Christina Tsien, Julie M. Vose, Joachim Yahalom, Nadeem Zafar, Mary Dwyer and Hema Sundar

Non-Hodgkin’s lymphomas (NHL) are a heterogeneous group of lymphoproliferative disorders originating in B lymphocytes, T lymphocytes, or natural killer cells. Mantle cell lymphoma (MCL) accounts for approximately 6% of all newly diagnosed NHL cases. Radiation therapy with or without systemic therapy is a reasonable approach for the few patients who present with early-stage disease. Rituximab-based chemoimmunotherapy followed by high-dose therapy and autologous stem cell rescue (HDT/ASCR) is recommended for patients presenting with advanced-stage disease. Induction therapy followed by rituximab maintenance may provide extended disease control for those who are not candidates for HDT/ASCR. Ibrutinib, a Bruton tyrosine kinase inhibitor, was recently approved for the treatment of relapsed or refractory disease. This manuscript discusses the recommendations outlined in the NCCN Guidelines for NHL regarding the diagnosis and management of patients with MCL.

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Andrew D. Zelenetz, Leo I. Gordon, William G. Wierda, Jeremy S. Abramson, Ranjana H. Advani, C. Babis Andreadis, Nancy Bartlett, John C. Byrd, Myron S. Czuczman, Luis E. Fayad, Richard I. Fisher, Martha J. Glenn, Thomas M. Habermann, Nancy Lee Harris, Richard T. Hoppe, Steven M. Horwitz, Christopher R. Kelsey, Youn H. Kim, Susan Krivacic, Ann S. LaCasce, Auayporn Nademanee, Pierluigi Porcu, Oliver Press, Rachel Rabinovitch, Nishitha Reddy, Erin Reid, Ayman A. Saad, Lubomir Sokol, Lode J. Swinnen, Christina Tsien, Julie M. Vose, Lynn Wilson, Joachim Yahalom, Nadeem Zafar, Mary Dwyer and Hema Sundar

Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are different manifestations of the same disease, which are managed in the same way. The advent of novel monoclonal antibodies (ofatumumab and obinutuzumab) led to the development of effective chemoimmunotherapy regimens. The recently approved small molecule kinase inhibitors (ibrutinib and idelalisib) are effective treatment options for CLL in elderly patients with decreased tolerance for aggressive regimens and in patients with poor prognostic features who do not benefit from conventional chemoimmunotherapy regimens. This portion of the NCCN Guidelines for Non-Hodgkin’s Lymphomas describes the recent specific to the incorporation of recently approved targeted therapies for the management of patients with newly diagnosed and relapsed or refractory CLL/SLL.

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Andrew D. Zelenetz, Leo I. Gordon, William G. Wierda, Jeremy S. Abramson, Ranjana H. Advani, C. Babis Andreadis, Nancy Bartlett, Naresh Bellam, John C. Byrd, Myron S. Czuczman, Luis E. Fayad, Richard I. Fisher, Martha J. Glenn, Nancy Lee Harris, Richard T. Hoppe, Steven M. Horwitz, Christopher R. Kelsey, Youn H. Kim, Susan Krivacic, Ann S. LaCasce, Auayporn Nademanee, Pierluigi Porcu, Oliver Press, Rachel Rabinovitch, Nishitha Reddy, Erin Reid, Lubomir Sokol, Lode J. Swinnen, Christina Tsien, Julie M. Vose, Joachim Yahalom, Nadeem Zafar, Mary Dwyer and Hema Sundar

Non-Hodgkin’s lymphomas (NHLs) are a heterogeneous group of lymphoproliferative disorders originating in B lymphocytes, T lymphocytes, or natural killer cells. Follicular lymphoma (FL) is the most common subtype of indolent NHL, accounting for approximately 22% of all newly diagnosed cases of NHL. The incorporation of rituximab to chemotherapy regimens has become a widely accepted standard of care for first-line therapy for patients with FL. Maintenance and consolidation therapy with rituximab and radioimmunotherapy have also been associated with improved progression-free survival in patients experiencing response to first-line therapy. Despite therapeutic advances that have improved outcomes, FL is generally considered a chronic disease characterized by multiple recurrences with current therapies. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with FL.

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Andrew D. Zelenetz, Jeremy S. Abramson, Ranjana H. Advani, C. Babis Andreadis, Nancy Bartlett, Naresh Bellam, John C. Byrd, Myron S. Czuczman, Luis E. Fayad, Martha J. Glenn, Jon P. Gockerman, Leo I. Gordon, Nancy Lee Harris, Richard T. Hoppe, Steven M. Horwitz, Christopher R. Kelsey, Youn H. Kim, Ann S. LaCasce, Auayporn Nademanee, Pierluigi Porcu, Oliver Press, Barbara Pro, Nashitha Reddy, Lubomir Sokol, Lode J. Swinnen, Christina Tsien, Julie M. Vose, William G. Wierda, Joachim Yahalom and Nadeem Zafar