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Hematology/oncology Clinics of North America

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https://www.readbyqxmd.com/read/30190026/waldenstr%C3%A3-m-macroglobulinemia-lessons-learned-from-basic-and-clinical-research
#1
EDITORIAL
Jorge J Castillo, Efstathios Kastritis, Steven P Treon
No abstract text is available yet for this article.
October 2018: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/30190025/novel-approaches-in-waldenstr%C3%A3-m-macroglobulinemia
#2
REVIEW
Michael A Spinner, Gaurav Varma, Ranjana H Advani
Recent advances in the understanding of Waldenström macroglobulinemia (WM) biology have paved the way for development of a plethora of novel therapeutic strategies. The success of ibrutinib in WM has shifted treatment paradigms away from conventional chemoimmunotherapy approaches. Recognition of high-risk genomic subgroups as well as mechanisms of acquired resistance to ibrutinib have led to targeting of additional pathways. In this article, the authors review ongoing and emerging trials of novel therapies in WM that target the B-cell receptor pathway beyond ibrutinib, toll-like receptor pathway, chemokine signaling, apoptotic pathway, chromatin remodeling, protein transport, the immune microenvironment, and CD19-directed immunotherapy...
October 2018: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/30190024/high-dose-therapy-and-hematopoietic-stem-cell-transplantation-in-waldenstr%C3%A3-m-macroglobulinemia
#3
REVIEW
Charalampia Kyriakou
Waldenström macroglobulinemia (WM) is an indolent low-grade non-Hodgkin lymphoma characterized by bone marrow infiltration by lymphoplasmacytic cells and associated clonal IgM paraproteinemia. Recent insights into the biology and genomic characteristics of WM have provided a further platform for more targeted therapies. Despite the high response rates and better depth and duration of responses, the disease remains incurable. This review focuses on use of the high-dose therapy with either autologous or allogeneic hematopoietic stem cell transplantation...
October 2018: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/30190023/first-generation-and-second-generation-bruton-tyrosine-kinase-inhibitors-in-waldenstr%C3%A3-m-macroglobulinemia
#4
REVIEW
Kimon V Argyropoulos, M Lia
Waldenström macroglobulinemia (WM) is an indolent B-cell lymphoma that is heavily dependent on Bruton tyrosine kinase (BTK) hyperactivation. Ibrutinib is a first-generation BTK inhibitor that has shown high activity and durable responses in patients with relapsed/refractory WM. Newer and more selective BTK inhibitors are currently being tested in several clinical trials and are expected to address the toxicity and the acquired resistance observed in patients receiving ibrutinib. Updates on ibrutinib and second-generation BTK inhibitors are summarized in this review...
October 2018: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/30190022/monoclonal-antibodies-for-waldenstr%C3%A3-m-macroglobulinemia
#5
REVIEW
Andres Dominguez, Efstathios Kastritis, Jorge J Castillo
For the last 2 decades, anti-CD20 monoclonal antibodies have revolutionized the treatment of patients with B-cell lymphomas. These agents have shown efficacy when used as single agents and also have improved response and survival rates when added to chemotherapy. Monoclonal antibodies are safe and effective as well in patients with Waldenström macroglobulinemia (WM). The purpose of this article is to review the mechanism of action of monoclonal antibodies and to discuss current clinical data supporting their use in patients with WM...
October 2018: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/30190021/proteasome-inhibitors-in-waldenstr%C3%A3-m-macroglobulinemia
#6
REVIEW
Efstathios Kastritis, Meletios A Dimopoulos
Waldenström macroglobulinemia (WM) remains an incurable B-cell lymphoproliferative disorder, yet therapy is only considered for patients with symptomatic disease. Primary therapy options for WM include combinations based on anti-CD20 monoclonal antibodies, mainly rituximab. However, proteasome inhibitors have become an important part of WM therapy both as primary therapy and as salvage option. Bortezomib is the proteasome inhibitor most studied and with extensive clinical experience, but new proteasome inhibitors (carfilzomib, ixazomib, oprozomib), with different toxicity profiles, routes of administration, and probably with preserved or improved activity, have become available and may also find their way into WM therapy...
October 2018: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/30190020/alkylating-agents-in-the-treatment-of-waldenstr%C3%A3-m-macroglobulinemia
#7
REVIEW
Christian Buske
The introduction of ibrutinib has grossly changed the treatment landscape in patients with Waldenström's Macroglobulinemia. Nevertheless, chemotherapy in combination with rituximab is still a cornerstone treatment. Among chemotherapeutics, alkylating agents are most frequently used. Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is a highly effective but potentially neurotoxic regimen. Dexamethasone, rituximab, and cyclophosphamide (DRC) induces long responses and has a favorable toxicity profile...
October 2018: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/30190019/initial-evaluation-of-the-patient-with-waldenstr%C3%A3-m-macroglobulinemia
#8
REVIEW
Jorge J Castillo, Steven P Treon
The initial evaluation of the patient with Waldenström macroglobulinemia can be challenging. Not only is it a rare disease, but the clinical features can vary greatly from patient to patient. In this article, we aim at providing concise and practical recommendations for the initial evaluation of patients with Waldenström macroglobulinemia, specifically regarding history taking, physical examination, laboratory testing, bone marrow aspiration, and biopsy evaluation and imaging studies. We then review the most common special clinical situations seen in patients with Waldenström macroglobulinemia, especially anemia, hyperviscosity, cryoglobulinemia, peripheral neuropathy, extramedullary disease, Bing-Neel syndrome, and amyloidosis...
October 2018: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/30190018/familial-waldenstr%C3%A3-m-macroglobulinemia-families-informing-populations
#9
REVIEW
Mary L McMaster
Familial clustering of Waldenström macroglobulinemia (WM) has been observed for nearly 6 decades. Family studies have provided seminal observations in delineating the phenotypic spectrum of WM susceptibility and confirming the importance of immunoglobulin M (IgM) monoclonal gammopathy of undetermined significance (IgM MGUS) as a precursor condition for WM, providing the rationale for large population-based epidemiologic studies of IgM MGUS and WM, and providing both the basis and the material for ongoing genetic studies aimed at identifying WM predisposition genes...
October 2018: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/30190017/the-bone-marrow-microenvironment-in-waldenstr%C3%A3-m-macroglobulinemia
#10
REVIEW
Shahrzad Jalali, Stephen M Ansell
Waldenström macroglobulinemia (WM) is an indolent B-cell lymphoma defined predominantly by infiltration of lymphoplasmacytic cells into the bone marrow (BM) and increased production of monoclonal immunoglobulin M (IgM) by lymphoplasmacytic cells, and the secretion of IgM is enhanced by cytokines in the bone marrow microenvironment. This article highlights the available data regarding the interaction of WM cells with both the cellular and noncellular compartments of the BM microenvironment and discusses how the BM promotes malignant cell growth and increases IgM production in this disease...
October 2018: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/30190016/flow-cytometry
#11
REVIEW
Amaia Gascue, Juana Merino, Bruno Paiva
Multiparameter flow cytometry (MFC) is valuable in the diagnosis and monitoring of most hematological malignancies. Although the assessment of cellular infiltrates in Waldenström macroglobulinemia (WM) relies on morphology and immunohistochemistry grounds, there is evidence pointing to the clinical significance of MFC in this disease. Herein, the authors review immunophenotypic patterns of B-cell development, the antigen profile of the WM clone and its normal B-cell counterpart, the clinical applicability of MFC in the differential diagnosis of immunoglobulin M-secreting lymphoproliferative disorders and monoclonal gammopathies, and its potential role in detecting minimal residual disease and monitoring treatment efficacy in WM...
October 2018: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/30190015/working-toward-a-genomic-prognostic-classification-of-waldenstr%C3%A3-m-macroglobulinemia-c-x-c-chemokine-receptor-type-4-mutation-and-beyond
#12
REVIEW
Marion Magierowicz, Cécile Tomowiak, Xavier Leleu, Stéphanie Poulain
Waldenström macroglobulinemia is a rare indolent B-cell lymphoma. Whole-exome sequencing studies have improved our knowledge of the Waldenström macroglobulinemia mutational landscape. The MYD88 L265P mutation is present in nearly 90% of patients with Waldenström macroglobulinemia. CXCR4 mutations are identified in approximately 30% of MYD88L265P cases and have been associated with ibrutinib resistance in clinical trials. Mutations in CD79B, ARID1a, or TP53 were described at lower frequency. Deciphering the earliest initiating lesions and identifying the molecular alterations leading to disease progression currently represent important goals in the future to identify the most relevant targets for precision therapy in Waldenström macroglobulinemia...
October 2018: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/30190014/genomic-landscape-of-waldenstr%C3%A3-m-macroglobulinemia
#13
REVIEW
Steven P Treon, Lian Xu, Xia Liu, Zachary R Hunter, Guang Yang, Jorge J Castillo
Next-generation sequencing has revealed recurring somatic mutations in Waldenström macroglobulinemia (WM). Common mutations include MYD88 (95%-97%), as well as CXCR4 (30%-40%), ARID1A (17%), and CD79B (8%-15%), which are typically found in MYD88-mutated patients. The genomic findings provide important insights into the pathogenesis, prognostication, and treatment outcome in WM. We discuss the genomic landscape of WM, and the impact of underlying genomics on disease presentation, transcriptional changes, treatment outcome, and overall survival impact...
October 2018: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/30047424/acquired-and-inherited-bone-marrow-failure-syndromes
#14
EDITORIAL
Colin A Sieff
No abstract text is available yet for this article.
August 2018: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/30047423/monosomy-7-in-pediatric-myelodysplastic-syndromes
#15
REVIEW
Marcin W Wlodarski, Sushree S Sahoo, Charlotte M Niemeyer
Myelodysplastic syndromes (MDS) in children and adolescents are a rare heterogeneous group of clonal stem cell disorders. Complete or partial loss of chromosome 7 constitutes the most common cytogenetic abnormality encountered in any type of childhood MDS, is associated with more advanced disease, and usually requires a timely allogeneic stem cell transplantation. This article provides insights into the current understanding of the genotype, phenotype, and clonal evolution patterns in pediatric MDS associated with loss of chromosome 7...
August 2018: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/30047422/germline-gata2-mutation-and-bone-marrow-failure
#16
REVIEW
Lisa J McReynolds, Katherine R Calvo, Steven M Holland
GATA2 deficiency is an immunodeficiency and bone marrow failure disorder caused by pathogenic variants in GATA2. It is inherited in an autosomal-dominant pattern or can be due to de novo sporadic germline mutation. Patients commonly have B-cell, dendritic cell, natural killer cell, and monocytopenias, and are predisposed to myelodysplastic syndrome, acute myeloid leukemia, and chronic myelomonocytic leukemia. Patients may suffer from disseminated human papilloma virus and mycobacterial infections, pulmonary alveolar proteinosis, and lymphedema...
August 2018: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/30047421/critical-issues-in-diamond-blackfan-anemia-and-prospects-for-novel-treatment
#17
REVIEW
Hojun Li, Harvey F Lodish, Colin A Sieff
Diamond-Blackfan anemia (DBA) is a severe congenital hypoplastic anemia caused by mutation in a ribosomal protein gene. Major clinical issues concern the optimal management of patients resistant to steroids, the first-line therapy. Hematopoietic stem cell transplantation is indicated in young patients with an HLA-matched unaffected sibling donor, and recent results with matched unrelated donor transplants indicate that these patients also do well. When neither steroids nor a transplant is possible red cell transfusions are required, and iron loading is rapid in some DBA patients, so effective chelation is vital...
August 2018: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/30047420/diagnosis-treatment-and-molecular-pathology-of-shwachman-diamond-syndrome
#18
REVIEW
Adam S Nelson, Kasiani C Myers
Shwachman-Diamond syndrome (SDS) is an inherited bone marrow failure syndrome classically associated with exocrine pancreatic dysfunction and neutropenia, with a predisposition toward progressive marrow failure, risk of myelodysplastic syndrome, and leukemia. Most patients carry biallelic mutations in the Shwachman-Bodian-Diamond Syndrome gene, which is an integral component of ribosome maturation and biogenesis. This article reviews the diagnosis, clinical characteristics, and treatment modalities of SDS, and reports advances in the understanding of the molecular pathophysiology of SDS...
August 2018: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/30047419/evaluation-and-management-of-hematopoietic-failure-in-dyskeratosis-congenita
#19
REVIEW
Suneet Agarwal
Dyskeratosis congenita (DC) is a rare, inherited bone marrow failure (BMF) syndrome characterized by variable manifestations and ages of onset, and predisposition to cancer. DC is one of a spectrum of diseases caused by mutations in genes regulating telomere maintenance, collectively referred to as telomere biology disorders (TBDs). Hematologic disease is common in children with DC/TBD. Timely diagnosis of underlying TBD in patients with BMF affects treatment and has been facilitated by increased awareness and availability of diagnostic tests in recent years...
August 2018: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/30047418/myelodysplastic-syndrome-acute-myeloid-leukemia-and-cancer-surveillance-in-fanconi-anemia
#20
REVIEW
Sharon A Savage, Michael F Walsh
Fanconi anemia (FA) is a DNA repair disorder associated with a high risk of cancer and bone marrow failure. Patients with FA may present with certain dysmorphic features, such as radial ray abnormalities, short stature, typical facies, bone marrow failure, or certain solid malignancies. Some patients may be recognized due to exquisite sensitivity after exposure to cancer therapy. FA is diagnosed by increased chromosomal breakage after exposure to clastogenic agents. It follows autosomal recessive and X-linked inheritance depending on the underlying genomic alterations...
August 2018: Hematology/oncology Clinics of North America
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