ABSTRACT
Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are essentially different manifestations of the same disease that are similarly managed. A number of molecular and cytogenetic variables with prognostic implications have been identified. Undetectable minimal residual disease at the end of treatment with chemoimmunotherapy or venetoclax-based combination regimens is an independent predictor of improved survival among patients with previously untreated or relapsed/refractory CLL/SLL. The selection of treatment is based on the disease stage, presence or absence of del(17p) or TP53 mutation, immunoglobulin heavy chain variable region mutation status, patient age, performance status, comorbid conditions, and the agent's toxicity profile. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with CLL/SLL.
Subject(s)
Leukemia, Lymphocytic, Chronic, B-Cell , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Prognosis , ImmunotherapyABSTRACT
Chronic myeloid leukemia (CML) is defined by the presence of Philadelphia chromosome resulting from a reciprocal translocation between chromosomes 9 and 22 [t9;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 in developed countries. Tyrosine kinase inhibitor (TKI) therapy is a highly effective treatment option for patients with chronic phase-CML. The primary goal of TKI therapy in patients with chronic phase-CML is to prevent disease progression to accelerated phase-CML or blast phase-CML. Discontinuation of TKI therapy with careful monitoring is feasible in selected patients. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with chronic phase-CML.
Subject(s)
Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Leukemia, Myeloid, Chronic-Phase , Humans , Blast Crisis/chemically induced , Blast Crisis/drug therapy , Blast Crisis/genetics , Protein Kinase Inhibitors/adverse effects , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Philadelphia Chromosome , Leukemia, Myeloid, Chronic-Phase/drug therapy , Fusion Proteins, bcr-abl/geneticsABSTRACT
Novel targeted therapies (small molecule inhibitors, antibody-drug conjugates, and CD19-directed therapies) have changed the treatment landscape of relapsed/refractory B-cell lymphomas. Bruton's tyrosine kinase (BTK) inhibitors continue to evolve in the management of mantle cell lymphoma (MCL), in both the relapsed/refractory and the frontline setting. Anti-CD19 CAR T-cell therapies are now effective and approved treatment options for relapsed/refractory follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and MCL. Bispecific T-cell engagers represent a novel immunotherapeutic approach for relapsed FL and DLBCL after multiple lines of therapies, including prior CAR T-cell therapy. These NCCN Guideline Insights highlight the significant updates to the NCCN Guidelines for B-Cell Lymphomas for the treatment of FL, DLBCL, and MCL.
Subject(s)
Lymphoma, Follicular , Lymphoma, Large B-Cell, Diffuse , Lymphoma, Mantle-Cell , Humans , Adult , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Follicular/drug therapy , Lymphoma, Mantle-Cell/drug therapy , Lymphoma, Mantle-Cell/pathology , Immunotherapy, Adoptive , T-LymphocytesABSTRACT
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pediatric Aggressive Mature B-Cell Lymphomas include recommendations for the diagnosis and management of pediatric patients with primary mediastinal large B-cell lymphoma (PMBL) and sporadic variants of Burkitt lymphoma and diffuse large B-cell lymphoma. PMBL is now considered as a distinct entity arising from mature thymic B-cells accounting for 2% of mature B-cell lymphomas in children and adolescents. This discussion section includes the recommendations outlined in the NCCN Guidelines for the diagnosis and management of pediatric patients with PMBL.
Subject(s)
Lymphoma, Large B-Cell, Diffuse , Adolescent , Humans , Child , Lymphoma, Large B-Cell, Diffuse/pathology , Medical OncologyABSTRACT
Gastrointestinal stromal tumors (GIST) are the most common type of soft tissue sarcoma that occur throughout the gastrointestinal tract. Most of these tumors are caused by oncogenic activating mutations in the KIT or PDGFRA genes. The NCCN Guidelines for GIST provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with these tumors. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including revised systemic therapy options for unresectable, progressive, or metastatic GIST based on mutational status, and updated recommendations for the management of GIST that develop resistance to specific tyrosine kinase inhibitors.
Subject(s)
Gastrointestinal Stromal Tumors , Humans , Gastrointestinal Stromal Tumors/diagnosis , Gastrointestinal Stromal Tumors/genetics , Gastrointestinal Stromal Tumors/therapy , Receptor, Platelet-Derived Growth Factor alpha/genetics , Proto-Oncogene Proteins c-kit/genetics , MutationABSTRACT
Soft tissue sarcomas (STS) are rare malignancies of mesenchymal cell origin that display a heterogenous mix of clinical and pathologic characteristics. STS can develop from fat, muscle, nerves, blood vessels, and other connective tissues. The evaluation and treatment of patients with STS requires a multidisciplinary team with demonstrated expertise in the management of these tumors. The complete NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Soft Tissue Sarcoma provide recommendations for the diagnosis, evaluation, and treatment of extremity/superficial trunk/head and neck STS, as well as retroperitoneal/intra-abdominal STS, desmoid tumors, and rhabdomyosarcoma. This portion of the NCCN Guidelines discusses general principles for the diagnosis and treatment of retroperitoneal/intra-abdominal STS, outlines treatment recommendations, and reviews the evidence to support the guidelines recommendations.
Subject(s)
Sarcoma , Soft Tissue Neoplasms , Extremities/pathology , Humans , Medical Oncology , Sarcoma/drug therapy , Sarcoma/therapy , Soft Tissue Neoplasms/diagnosis , Soft Tissue Neoplasms/pathology , Soft Tissue Neoplasms/therapyABSTRACT
The treatment landscape of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) has significantly evolved in recent years. Targeted therapy with Bruton's tyrosine kinase (BTK) inhibitors and BCL-2 inhibitors has emerged as an effective chemotherapy-free option for patients with previously untreated or relapsed/refractory CLL/SLL. Undetectable minimal residual disease after the end of treatment is emerging as an important predictor of progression-free and overall survival for patients treated with fixed-duration BCL-2 inhibitor-based treatment. These NCCN Guidelines Insights discuss the updates to the NCCN Guidelines for CLL/SLL specific to the use of chemotherapy-free treatment options for patients with treatment-naïve and relapsed/refractory disease.
Subject(s)
Antineoplastic Agents , Leukemia, Lymphocytic, Chronic, B-Cell , Lymphoma, B-Cell , Antineoplastic Agents/therapeutic use , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Neoplasm, Residual , Proto-Oncogene Proteins c-bcl-2/therapeutic useABSTRACT
Hodgkin lymphoma (HL) is an uncommon malignancy of B-cell origin. Classical HL (cHL) and nodular lymphocyte-predominant HL are the 2 main types of HL. The cure rates for HL have increased so markedly with the advent of modern treatment options that overriding treatment considerations often relate to long-term toxicity. These NCCN Guidelines Insights discuss the recent updates to the NCCN Guidelines for HL focusing on (1) radiation therapy dose constraints in the management of patients with HL, and (2) the management of advanced-stage and relapsed or refractory cHL.
Subject(s)
Hodgkin Disease , Hodgkin Disease/diagnosis , Hodgkin Disease/radiotherapy , HumansABSTRACT
Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of lymphoproliferative disorders arising from mature T cells, accounting for about 10% of non-Hodgkin lymphomas. PTCL-not otherwise specified is the most common subtype, followed by angioimmunoblastic T-cell lymphoma, anaplastic large cell lymphoma, anaplastic lymphoma kinase-positive, anaplastic large cell lymphoma, anaplastic lymphoma kinase-negative, and enteropathy-associated T-cell lymphoma. This discussion section focuses on the diagnosis and treatment of PTCLs as outlined in the NCCN Guidelines for T-Cell Lymphomas.
Subject(s)
Immunoblastic Lymphadenopathy , Lymphoma, T-Cell, Peripheral , Lymphoma, T-Cell , Humans , Immunoblastic Lymphadenopathy/diagnosis , Immunoblastic Lymphadenopathy/pathology , Immunoblastic Lymphadenopathy/therapy , Lymphoma, T-Cell/diagnosis , Lymphoma, T-Cell/therapy , Lymphoma, T-Cell, Peripheral/diagnosis , Lymphoma, T-Cell, Peripheral/therapyABSTRACT
AbstractAll else equal, parasites that harm host fitness should depress densities of their hosts. However, parasites that alter host traits may increase host density via indirect ecological interactions. Here, we show how depression of foraging rate of infected hosts can produce such a hydra effect. Using a foraging assay, we quantified reduced foraging rates of a zooplankton host infected with a virulent fungal parasite. We then parameterized a dynamical model of hosts, parasites, and resources with this foraging function, showing how foraging depression can create a hydra effect. Mathematically, the hydra arose when increased resource productivity exceeded any increase in resource consumption per host. Therefore, the foraging-mediated hydra effect more likely emerged (1) for hosts that strongly control logistic-like resources and (2) during larger epidemics of moderately virulent parasites. We then analyzed epidemics from 13 fungal epidemics in nature. We found evidence for a foraging-mediated hydra effect: large outbreaks depressed foraging rate and correlated with increased densities of both algal resources and Daphnia hosts. Therefore, depression of the foraging rate of infected hosts can produce higher host densities even during epidemics of parasites that increase host mortality. Such hydras might prevent the collapse of host populations but also could produce higher densities of infected hosts.
Subject(s)
Epidemics , Parasites , Animals , Daphnia , Fungi , Host-Parasite Interactions , ZooplanktonABSTRACT
In the last decade, a better understanding of the molecular pathogenesis of B-cell non-Hodgkin lymphomas has resulted in the development of novel targeted therapies, such as small molecule inhibitors of select kinases in the B-cell receptor pathway, antibody-drug conjugates, and small molecules that target a variety of proteins (eg, CD-19, EZH2, and XPO-1-mediated nuclear export). Anti-CD19 CAR T-cell therapy, first approved for relapsed/refractory (R/R) diffuse large B-cell lymphoma, has also emerged as a novel treatment option for R/R follicular lymphoma and mantle cell lymphoma. These NCCN Guideline Insights highlight the new targeted therapy options included in the NCCN Guidelines for B-Cell Lymphomas for the treatment of R/R disease.
Subject(s)
Immunoconjugates , Lymphoma, Large B-Cell, Diffuse , Lymphoma, Non-Hodgkin , Adult , Antigens, CD19 , Humans , Immunoconjugates/therapeutic use , Immunotherapy, Adoptive/methods , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Non-Hodgkin/drug therapyABSTRACT
The NCCN Guidelines for Older Adult Oncology address specific issues related to the management of cancer in older adults, including screening and comprehensive geriatric assessment (CGA), assessing the risks and benefits of treatment, preventing or decreasing complications from therapy, and managing patients deemed to be at high risk for treatment-related toxicity. CGA is a multidisciplinary, in-depth evaluation that assesses the objective health of the older adult while evaluating multiple domains, which may affect cancer prognosis and treatment choices. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines providing specific practical framework for the use of CGA when evaluating older adults with cancer.
Subject(s)
Medical Oncology , Neoplasms , Aged , Geriatric Assessment , Humans , Mass Screening , Neoplasms/complications , Neoplasms/diagnosis , Neoplasms/therapyABSTRACT
Hepatosplenic T-cell lymphoma (HSTCL) is a rare subtype of T-cell lymphoma associated with an aggressive clinical course and a worse prognosis. HSTCL develops in the setting of chronic immune suppression or immune dysregulation in up to 20% of cases and is most often characterized by spleen, liver, and bone marrow involvement. Diagnosis and management of HSTCL pose significant challenges given the rarity of the disease along with the absence of lymphadenopathy and poor outcome with conventional chemotherapy regimens. These Guidelines Insights focus on the diagnosis and treatment of HSTCL as outlined in the NCCN Guidelines for T-Cell Lymphomas.
Subject(s)
Lymphoma, T-Cell , Humans , Lymphoma, T-Cell/diagnosis , Lymphoma, T-Cell/epidemiology , Lymphoma, T-Cell/therapy , Practice Guidelines as Topic , PrognosisABSTRACT
Chronic myeloid leukemia (CML) is defined by the presence of Philadelphia chromosome (Ph) which results 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 therapy is a highly effective first-line treatment option for all patients with newly diagnosed chronic phase CML. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with chronic phase CML.
Subject(s)
Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Leukemia, Myeloid, Chronic-Phase , Fusion Proteins, bcr-abl/genetics , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Medical Oncology , Philadelphia Chromosome , Translocation, GeneticABSTRACT
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.
Subject(s)
Eosinophilia , Myeloproliferative Disorders , Neoplasms , Eosinophilia/diagnosis , Eosinophilia/genetics , Humans , Myeloproliferative Disorders/diagnosis , Myeloproliferative Disorders/genetics , Myeloproliferative Disorders/therapy , Oncogene Proteins, Fusion/geneticsABSTRACT
Mycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma (CTCL), and Sézary syndrome (SS) is a rare erythrodermic and leukemic subtype of CTCL characterized by significant blood involvement. Although early-stage disease can be effectively treated predominantly with skin-directed therapies, systemic therapy is often necessary for the treatment of advanced-stage disease. Systemic therapy options have evolved in recent years with the approval of novel agents such as romidepsin, brentuximab vedotin, and mogamulizumab. These NCCN Guidelines Insights discuss the diagnosis and management of MF and SS (with a focus on systemic therapy).
Subject(s)
Lymphoma, T-Cell, Cutaneous/pathology , Mycosis Fungoides/diagnosis , Skin Neoplasms/pathology , Guidelines as Topic , Humans , Mycosis Fungoides/pathologyABSTRACT
Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are characterized by a progressive accumulation of leukemic cells in the peripheral blood, bone marrow, and lymphoid tissues. Treatment of CLL/SLL has evolved significantly in recent years because of the improved understanding of the disease biology and the development of novel targeted therapies. In patients with indications for initiating treatment, the selection of treatment should be based on the disease stage, patient's age and overall fitness (performance status and comorbid conditions), and cytogenetic abnormalities. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with CLL/SLL.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/standards , Hematopoietic Stem Cell Transplantation/standards , Leukemia, Lymphocytic, Chronic, B-Cell/therapy , Medical Oncology/standards , Neoplasm Recurrence, Local/therapy , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/analysis , Biomarkers, Tumor/genetics , Bone Marrow/pathology , Disease-Free Survival , Drug Resistance, Neoplasm/genetics , Hematopoietic Stem Cell Transplantation/methods , Humans , Immunophenotyping , Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Leukemia, Lymphocytic, Chronic, B-Cell/mortality , Lymph Nodes/cytology , Lymph Nodes/pathology , Lymphocytes/pathology , Medical Oncology/methods , Mutation , Neoplasm Recurrence, Local/epidemiology , Neoplasm Staging , Organizations, Nonprofit/standards , Prognosis , Remission Induction/methods , Transplantation, Homologous/standards , United States/epidemiologyABSTRACT
Diffuse large B-cell lymphomas (DLBCLs) and follicular lymphoma (FL) are the most common subtypes of B-cell non-Hodgkin's lymphomas in adults. Histologic transformation of FL to DLBCL (TFL) occurs in approximately 15% of patients and is generally associated with a poor clinical outcome. Phosphatidylinositol 3-kinase (PI3K) inhibitors have shown promising results in the treatment of relapsed/refractory FL. CAR T-cell therapy (axicabtagene ciloleucel and tisagenlecleucel) has emerged as a novel treatment option for relapsed/refractory DLBCL and TFL. These NCCN Guidelines Insights highlight important updates to the NCCN Guidelines for B-Cell Lymphomas regarding the treatment of TFL and relapsed/refractory FL and DLBCL.
Subject(s)
Lymphoma, Follicular/therapy , Lymphoma, Large B-Cell, Diffuse/therapy , Medical Oncology/standards , Neoplasm Recurrence, Local/therapy , Adult , Aftercare/standards , Antineoplastic Agents, Immunological/standards , Antineoplastic Agents, Immunological/therapeutic use , Drug Resistance, Neoplasm , Humans , Immunotherapy, Adoptive/methods , Immunotherapy, Adoptive/standards , Lymphoma, Follicular/immunology , Lymphoma, Follicular/mortality , Lymphoma, Follicular/pathology , Lymphoma, Large B-Cell, Diffuse/immunology , Lymphoma, Large B-Cell, Diffuse/mortality , Lymphoma, Large B-Cell, Diffuse/pathology , Medical Oncology/methods , Neoplasm Recurrence, Local/immunology , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Phosphoinositide-3 Kinase Inhibitors/standards , Phosphoinositide-3 Kinase Inhibitors/therapeutic use , Receptors, Chimeric Antigen/immunology , Signal Transduction/drug effects , Signal Transduction/immunology , United StatesABSTRACT
Chronic lymphocytic leukemia (CLL) is generally characterized by an indolent disease course. Histologic transformation (also known as Richter's transformation) to more aggressive lymphomas, such as diffuse large B-cell lymphoma or Hodgkin lymphoma, occurs in approximately 2% to 10% of patients and is associated with a poor prognosis. These NCCN Guidelines Insights discuss the recommendations for the diagnosis and management of patients with histologic transformation.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Medical Oncology/standards , Societies, Medical/standards , Antineoplastic Combined Chemotherapy Protocols/standards , Clinical Trials as Topic , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis , Leukemia, Lymphocytic, Chronic, B-Cell/etiology , Leukemia, Lymphocytic, Chronic, B-Cell/mortality , Medical Oncology/methods , Progression-Free Survival , United StatesABSTRACT
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.
