Search Results

You are looking at 1 - 10 of 11 items for

  • Author: B. Douglas Smith x
Clear All Modify Search
Full access

Susan O'Brien, Ellin Berman, Joseph O. Moore, Javier Pinilla-Ibarz, Jerald P. Radich, Paul J. Shami, B. Douglas Smith, David S. Snyder, Hema M. Sundar, Moshe Talpaz and Meir Wetzler

The advent of imatinib has dramatically improved outcomes in patients with chronic myelogenous leukemia (CML). It has become the standard of care for all patients with newly diagnosed chronic-phase CML based on its successful induction of durable responses in most patients. However, its use is complicated by the development of resistance in some patients. Dose escalation might overcome this resistance if detected early. The second-generation tyrosine kinase inhibitors (TKIs) dasatinib and nilotinib provide effective therapeutic options for managing patients resistant or intolerant to imatinib. Recent studies have shown that dasatinib and nilotinib provide quicker and potentially better responses than standard-dose imatinib when used as a first-line treatment. The goal of therapy for patients with CML is the achievement of a complete cytogenetic response, and eventually a major molecular response, to prevent disease progression to accelerated or blast phase. Selecting the appropriate TKI depends on many factors, including disease phase, primary or secondary resistance to TKI, the agent's side effect profile and its relative effectiveness against BCR-ABL mutations, and the patient's tolerance to therapy. In October 2010, NCCN organized a task force consisting of a panel of experts from NCCN Member Institutions with expertise in the management of patients with CML to discuss these issues. This report provides recommendations regarding the selection of TKI therapy for the management of patients with CML based on the evaluation of available published clinical data and expert opinion among the task force members.

Full access

Jerald P. Radich, Andrew D. Zelenetz, Wing C. Chan, Carlo M. Croce, Myron S. Czuczman, Harry P. Erba, Sandra J. Horning, Jane Houldsworth, B. Douglas Smith, David S. Snyder, Hema M. Sundar, Meir Wetzler and Jane N. Winter

The introduction of targeted therapies has revolutionized treatment and improved outcomes in patients with leukemias and lymphomas. However, many patients experience relapse caused by the persistence of residual malignant cells. Cytogenetic and molecular techniques are increasingly being used to assess and quantify minimal residual disease (MRD). The emergence of advanced technologies has led to the discovery of multiple novel molecular markers that can be used to detect MRD and predict outcome in patients with leukemias and lymphomas. Gene expression signatures that predict clinical outcomes in patients with non-Hodgkin's lymphoma have been identified. In chronic myelogenous leukemia, molecular monitoring has become more important in assessing response and detecting resistance to therapy. In acute leukemias, several new markers have shown potential in prognostication and monitoring treatment. In leukemias and lymphomas, microRNAs have been identified that may be useful in diagnostics and prognostication. To address these issues, the National Comprehensive Cancer Network (NCCN) organized a task force consisting of a panel of experts in leukemia and lymphoma to discuss recent advances in the field of molecular markers and monitoring MRD.

Full access

Susan O'Brien, Camille N. Abboud, Mojtaba Akhtari, Jessica Altman, Ellin Berman, Daniel J. DeAngelo, Steven Devine, Amir T. Fathi, Jason Gotlib, Madan Jagasia, Joseph O. Moore, Javier Pinilla-Ibarz, Jerald P. Radich, Vishnu V.B. Reddy, Neil P. Shah, Paul J. Shami, B. Douglas Smith, David S. Snyder, Meir Wetzler and Furhan Yunus

Full access

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...
Full access

Susan O'Brien, Ellin Berman, Hossein Borghaei, Daniel J. DeAngelo, Marcel P. Devetten, Steven Devine, Harry P. Erba, Jason Gotlib, Madan Jagasia, Joseph O. Moore, Tariq Mughal, Javier Pinilla-Ibarz, Jerald P. Radich, Neil P. Shah, Paul J. Shami, B. Douglas Smith, David S. Snyder, Martin S. Tallman, Moshe Talpaz and Meir Wetzler

Chronic Myelogenous Leukemia Clinical Practice Guidelines in Oncology NCCN Categories of Evidence and Consensus Category 1: The recommendation is based on high-level evidence (e.g., randomized controlled trials) and there is uniform NCCN consensus. Category 2A: The recommendation is based on lower-level evidence and there is uniform NCCN consensus. Category 2B: The recommendation is based on lower-level evidence and there is nonuniform NCCN consensus (but no major disagreement). Category 3: The recommendation is based on any level of evidence but reflects major disagreement. All recommendations are category 2A unless otherwise noted. Clinical trials: The NCCN believes that the best management for any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. Overview Chronic myelogenous leukemia (CML) accounts for 15% of adult leukemias. Although the median age of disease onset is 67 years, CML occurs in all age groups (Surveillance, Epidemiology, and End Results [SEER] statistics). In 2009, an estimated 5050 cases will be diagnosed and 470 patients will die from the disease in the United States.1 CML is a hematopoietic stem cell disease, which is characterized by a reciprocal translocation between chromosomes 9 and 22, resulting in the formation of the Philadelphia chromosome (Ph chromosome). This translocation t(9;22) results in the head-to-tail fusion of the breakpoint cluster region (BCR) gene on chromosome 22 at band q11 and the Abelson murine leukemia (ABL) gene located on chromosome 9 at band q34.2 The product of the fusion gene (BCR-ABL) is believed to play a central role in the...
Full access

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.

Full access

Susan O’Brien, Jerald P. Radich, Camille N. Abboud, Mojtaba Akhtari, Jessica K. Altman, Ellin Berman, Peter Curtin, Daniel J. DeAngelo, Michael Deininger, Steven Devine, Amir T. Fathi, Jason Gotlib, Madan Jagasia, Patricia Kropf, Joseph O. Moore, Arnel Pallera, Vishnu VB. Reddy, Neil P. Shah, B. Douglas Smith, David S. Snyder, Meir Wetzler, Kristina Gregory and Hema Sundar

Chronic myelogenous leukemia (CML) is usually diagnosed in the chronic phase. Untreated chronic phase CML will eventually progress to advanced phase (accelerated or blast phase) CML. Tyrosine kinase inhibitors (TKIs) have been shown to induce favorable response rates in patients with accelerated and blast phase CML. The addition of TKIs to chemotherapy has also been associated with improved outcomes in patients with blast phase CML. Allogeneic hematopoietic stem cell transplant remains a potentially curative option for patients with advanced phase CML, although treatment with a course of TKIs will be beneficial as a bridge to transplant. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with advanced phase CML.

Full access

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.

Full access

Susan O’Brien, Jerald P. Radich, Camille N. Abboud, Mojtaba Akhtari, Jessica K. Altman, Ellin Berman, Daniel J. DeAngelo, Michael Deininger, Steven Devine, Amir T. Fathi, Jason Gotlib, Madan Jagasia, Patricia Kropf, Joseph O. Moore, Arnel Pallera, Javier Pinilla-Ibarz, Vishnu VB. Reddy, Neil P. Shah, B. Douglas Smith, David S. Snyder, Meir Wetzler, Kristina Gregory and Hema Sundar

The 2014 NCCN Clinical Practice Guidelines in Oncology for Chronic Myelogenous Leukemia recommend quantitative reverse-transcription polymerase chain reaction (QPCR) standardized to International Scale (IS) as the preferred method for monitoring molecular response to tyrosine kinase inhibitor (TKI) therapy. A BCR-ABL1 transcript level of 10% or less (IS) is now included as the response milestone at 3 and 6 months. Change of therapy to an alternate TKI is recommended for patients with BCR-ABL1 transcript levels greater than 10% (IS) at 3 months after primary treatment with imatinib. Continuing the same dose of TKI or switching to an alternate TKI are options for patients with BCR-ABL1 transcript levels greater than 10% (IS) at 3 months after primary treatment with dasatinib or nilotinib. The guidelines recommend 6-month evaluation with QPCR (IS) for patients with BCR-ABL1 transcript levels greater than 10% at 3 months. Monitoring with QPCR (IS) every 3 months is recommended for all patients, including those who meet response milestones at 3, 6, 12, and 18 months (BCR-ABL1 transcript level ≤10% [IS] at 3 and 6 months, complete cytogenetic response at 12 and 18 months).

Full access

Arnel Pallera, Jessica K. Altman, Ellin Berman, Camille N. Abboud, Bhavana Bhatnagar, Peter Curtin, Daniel J. DeAngelo, Jason Gotlib, R. Tanner Hagelstrom, Gabriela Hobbs, Madan Jagasia, Hagop M. Kantarjian, Patricia Kropf, Leland Metheny, Joseph O. Moore, Evelena Ontiveros, Enkhtsetseg Purev, Albert Quiery, Vishnu V.B. Reddy, Michal G. Rose, Neil P. Shah, B. Douglas Smith, David S. Snyder, Kendra L. Sweet, Raoul Tibes, David T. Yang, Kristina Gregory, Hema Sundar, Michael Deininger and Jerald P. Radich

The NCCN Guidelines for Chronic Myeloid Leukemia (CML) provide recommendations for the management of chronic-phase and advanced-phase CML in adult patients. The median age of disease onset is 67 years. However, because CML occurs in all age groups, clinical care teams should be prepared to address issues relating to fertility and pregnancy with patients who are of reproductive age at the time of diagnosis. CML is relatively rare in children and there are no evidence-based recommendations for the management of CML in pediatric population. These NCCN Guidelines Insights discuss special considerations for the management of CML during pregnancy and for the management of CML in the pediatric population.