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Treatment of myeloma

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https://www.readbyqxmd.com/read/27923223/intestinal-pneumatosis-associated-with-tuberculosis-after-allogeneic-hematopoietic-stem-cell-transplantation
#1
Vivek Venkataramani, Ali Seif Amir Hosseini, Marco H Schulze, Lorenz Trümper, Gerald Wulf, Ulrike Bacher, Wolfram Jung
Pneumatosis intestinalis (PI), defined as intestinal intra- and extramural gas accumulation, is a rare radiographic finding in conditions of intestinal wall damage of varied etiology. Here, we report on a 56-year-old female with multiple myeloma who presented with undulating fever, fluctuating abdominal symptoms, and a distended abdomen 5 months after allogeneic hematopoietic stem cell transplantation (HSCT). Abdominal X-ray and CT scan documented PI with gas accumulation both in the intestinal and colonic bowel walls...
December 7, 2016: Acta Haematologica
https://www.readbyqxmd.com/read/27917682/the-preclinical-discovery-and-development-of-bortezomib-for-the-treatment-of-mantle-cell-lymphoma
#2
Richard Arkwright, Tri Minh Pham, Jeffrey A Zonder, Q Ping Dou
Introduction- Mantle cell lymphoma (MCL) is an incurable, often aggressive B-cell malignancy. Bortezomib (BTZ), the 20S proteasome inhibitor was originally developed and approved for treatment of relapsed refractory multiple myeloma, and subsequently approved for treatment of MCL. BTZ's single-agent activity induces clinical responses in approximately one-third of relapsed MCL patients. BTZ-containing combination therapies have further improved the quality and duration of clinical responses compared to standard chemotherapies in previously untreated MCL patients...
December 3, 2016: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/27917369/management-of-multiple-myeloma-and-usage-of-bortezomib-perspective-from-india-and-ukraine
#3
Amit Garg, Mykhaylo Morgunskyy, Yogesh Belagali, Namita Gupta, Shyam Prasad Akku
Novel treatment strategies have remarkably improved the multiple myeloma (MM) patients' survival, with associated increased costs. A joint panel meet of international experts from India and Ukraine was held in New Delhi on May 19, 2016 focusing on MM management, bortezomib role, unmet medical needs, and current challenges. The health-care system for oncology in India is majorly private vs. government-based in Ukraine. In India, electrophoresis, serum-free light chain assays, bone marrow tests, and X-rays are available modes of diagnosis...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27916918/subchronic-toxicities-of-hz1006-a-hydroxamate-based-histone-deacetylase-inhibitor-in-beagle-dogs-and-sprague-dawley-rats
#4
Xiaofang Zhang, Xiaodong Zhang, Bojun Yuan, Lijun Ren, Tianbao Zhang, Guocai Lu
Histone deacetylase inhibitors (HDACIs), such as vorinostat and panobinostat, have been shown to have active effects on many hematologic malignancies, including multiple myeloma and cutaneous T-cell lymphoma. Hydroxamate-based (Hb) HDACIs have very good toxicity profiles and are currently being tested in phases I and II clinical trials with promising results in selected neoplasms, such as bladder carcinoma. One of the Hb-HDACIs, HZ1006, has been demonstrated to be a promising drug for clinical use. The aim of our study was to determine the possible target of toxicity and to identify a non-toxic dose of HZ1006 for clinical use...
November 30, 2016: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/27916892/molecular-mechanisms-of-p53-deregulation-in-cancer-an-overview-in-multiple-myeloma
#5
REVIEW
Ana B Herrero, Elizabeta A Rojas, Irena Misiewicz-Krzeminska, Patryk Krzeminski, Norma C Gutiérrez
The p53 pathway is inactivated in the majority of human cancers. Although this perturbation frequently occurs through the mutation or deletion of p53 itself, there are other mechanisms that can attenuate the pathway and contribute to tumorigenesis. For example, overexpression of important p53 negative regulators, such as murine double minute 2 (MDM2) or murine double minute 4 (MDM4), epigenetic deregulation, or even alterations in TP53 mRNA splicing. In this work, we will review the different mechanisms of p53 pathway inhibition in cancer with special focus on multiple myeloma (MM), the second most common hematological malignancy, with low incidence of p53 mutations/deletions but growing evidence of indirect p53 pathway deregulation...
November 30, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27916078/-effects-of-ifosfamide-in-combination-with-pegylated-liposomal-doxorubicin-and-dexamethasone-in-the-treatment-of-relapsed-refractory-multiple-myeloma
#6
N An, M Shen, X Li, Z X Huang, S L Chen
Objective: To investigate the efficacy and adverse effects of ifosfamide in combination with pegylated liposomal doxorubicin and dexamethasone (CDD) in treating patients with relapsed/refractory multiple myeloma (MM). Methods: The clinical data of 30 relapsed/refractory MM patients treated with CDD regimen in Department of Hematology and Oncology of Beijing Chaoyang Hospital from November 2012 to November 2015 were retrospectively analyzed. The CDD treatment included ifosfamide 0.5-1.0 g/d on d1-4, pegylated liposomal doxorubicin 40-60 mg/d on d1, and dexamethasone 10-20 mg/d on d1-4...
November 29, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/27913860/improved-clinical-outcomes-for-multiple-myeloma-patients-treated-at-a-single-specialty-clinic
#7
Ariana Berenson, Suzie Vardanyan, Michael David, James Wang, Nika Manik Harutyunyan, Jillian Gottlieb, Ran Halleluyan, Tanya M Spektor, Kyle A Udd, Shahrooz Eshaghian, Youram Nassir, Benjamin Eades, Regina Swift, James R Berenson
Despite recent advances made in its treatment, multiple myeloma (MM) remains an incurable B cell malignancy. Thus, the objective for treating these patients is to prolong overall survival (OS) and preserve patients' quality of life. We have analyzed data from 264 consecutive MM patients who had their initial visit between July 1, 2004 and December 1, 2014 and have received treatment in a single clinic specializing in MM. We determined their progression-free survival (PFS, OS, and 5-year OS). The PFS for frontline (n = 165 treatments), salvage (n = 980), and all treatments (n = 1145) were 13...
December 2, 2016: Annals of Hematology
https://www.readbyqxmd.com/read/27913524/cellular-and-vaccine-immunotherapy-for-multiple-myeloma
#8
Alfred L Garfall, Edward A Stadtmauer
Allogeneic hematopoietic cell transplantation and donor lymphocyte infusion for multiple myeloma (MM) can induce graft-versus-myeloma immunity and long-term survivorship, but limited efficacy and associated toxicities have prevented its widespread use. Cellular immunotherapies and vaccines seek to induce more specific, reliable, and potent antimyeloma immune responses with less treatment-related risk than is possible with allogeneic transplantation. Advances in molecular biology, and basic and applied immunology, have led to promising approaches such as genetically engineered T cells with chimeric antigen receptors and T-cell receptors targeting myeloma-specific epitopes, vaccine primed ex vivo expanded autologous T cells, expanded marrow-infiltrating lymphocytes, and plasma cell/dendritic cell fusion vaccines...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913523/advances-and-practical-use-of-monoclonal-antibodies-in-multiple-myeloma-therapy
#9
Hans C Lee, Donna M Weber
The use of proteasome inhibitors and immunomodulatory agents in the treatment of myeloma have resulted in significant improvements in patient outcomes over the last decade. Although these agents now form the backbone of current myeloma treatment regimens both in the frontline and in a relapsed setting, drug resistance remains an inevitable challenge that most patients will encounter during their disease course. Hence, new treatment strategies continue to be explored, and the recent regulatory approvals of the monoclonal antibodies (mAbs) daratumumab (DARA) and elotuzumab (ELO), which target the plasma cell surface proteins CD38 and signaling lymphocytic activation molecule F7 (SLAMF7), respectively, have heralded the long-awaited era of antibody-based approaches in the treatment of myeloma...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913522/role-of-stem-cell-transplant-and-maintenance-therapy-in-plasma-cell-disorders
#10
Philip L McCarthy, Sarah A Holstein
Autologous stem cell transplant (ASCT) has been an important component of therapy for myeloma patients eligible for high-dose chemotherapy. Recent studies comparing early transplant to low-dose chemotherapy support the continued use of ASCT as consolidation following induction therapy, even in the era of immunomodulatory drugs, proteasome inhibitors, and other novel agents. Despite the marked improvements in outcomes with this approach, most patients will eventually experience disease progression. Thus, inclusion of post-ASCT consolidation/maintenance strategies is used to improve long-term disease control...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913521/sequencing-of-nontransplant-treatments-in-multiple-myeloma-patients-with-active-disease
#11
Andrew J Yee, Noopur S Raje
The approval of several different classes of drugs in recent years has resulted in a dramatic expansion of treatment options for multiple myeloma patients, improving both survival and quality of life. Lenalidomide and bortezomib are now core components of treatment both at time of diagnosis and at relapse. Next-generation immunomodulatory drugs, like pomalidomide, and newer proteasome inhibitors like carfilzomib and ixazomib are available for use at relapse. Drugs with novel mechanisms of action such as the histone deacetylase inhibitor panobinostat and the monoclonal antibodies targeting SLAMF7 (elotuzumab) and CD38 (daratumumab) are significant steps forward...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913520/myeloma-management-of-the-newly-diagnosed-high-risk-patient
#12
Angela Dispenzieri
Although there have been many definitions for high-risk (HR) myeloma, most recent consensus for classifying risk in patients with newly diagnosed multiple myeloma (NMM) comes from the International Myeloma Working Group. This recently published revised International Staging System includes del(17p) or t(4;14) by fluorescence in situ hybridization, β-2 microglobulin, albumin, and lactate dehydrogenase. These elements should be captured in all NMM patients. The optimal treatments for HR myeloma have not been fully worked out; therefore, these patients should be considered for clinical trials...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27912846/new-insights-and-evolving-role-of-pegylated-liposomal-doxorubicin-in-cancer-therapy
#13
REVIEW
Alberto A Gabizon, Yogita Patil, Ninh M La-Beck
We herein review various pharmacological and clinical aspects of pegylated liposomal doxorubicin (PLD), the first nanomedicine to be approved for cancer therapy, and discuss the gap between its potent antitumor activity in preclinical studies and its comparatively modest achievements in clinical studies and limited use in clinical practice. PLD is a complex formulation of doxorubicin based on pharmaceutical nanotechnology with unique pharmacokinetic and pharmacodynamic properties. Its long circulation time with stable retention of the payload and its accumulation in tumors with high vascular permeability both result in important advantages over conventional chemotherapy...
November 2016: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/27912844/heparanase-from-basic-research-to-therapeutic-applications-in-cancer-and-inflammation
#14
Israel Vlodavsky, Preeti Singh, Ilanit Boyango, Lilach Gutter-Kapon, Michael Elkin, Ralph D Sanderson, Neta Ilan
Heparanase, the sole heparan sulfate degrading endoglycosidase, regulates multiple biological activities that enhance tumor growth, angiogenesis and metastasis. Heparanase expression is enhanced in almost all cancers examined including various carcinomas, sarcomas and hematological malignancies. Numerous clinical association studies have consistently demonstrated that upregulation of heparanase expression correlates with increased tumor size, tumor angiogenesis, enhanced metastasis and poor prognosis. In contrast, knockdown of heparanase or treatments of tumor-bearing mice with heparanase-inhibiting compounds, markedly attenuate tumor progression further underscoring the potential of anti-heparanase therapy for multiple types of cancer...
November 2016: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/27911437/the-role-of-the-proteasome-in-aml
#15
REVIEW
C M Csizmar, D-H Kim, Z Sachs
Acute myeloid leukemia (AML) is deadly hematologic malignancy. Despite a well-characterized genetic and molecular landscape, targeted therapies for AML have failed to significantly improve clinical outcomes. Over the past decade, proteasome inhibition has been demonstrated to be an effective therapeutic strategy in several hematologic malignancies. Proteasome inhibitors, such as bortezomib and carfilzomib, have become mainstays of treatment for multiple myeloma and mantle cell lymphoma. In light of this success, there has been a surge of literature exploring both the role of the proteasome and the effects of proteasome inhibition in AML...
December 2, 2016: Blood Cancer Journal
https://www.readbyqxmd.com/read/27910963/daratumumab-monoclonal-antibody-therapy-to-treat-multiple-myeloma
#16
C Xia, M Ribeiro, S Scott, S Lonial
Daratumumab (Darzalex[TM]) is a human monoclonal antibody (MAb) that targets CD38; a surface protein highly expressed across multiple myeloma (MM) cells. Preclinical studies have shown daratumumab induces MM cell death through several mechanisms, including complement-dependent cytotoxicity (CDC) antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), apoptosis upon secondary crosslinking and immunomodulatory effects via a decrease in immune suppressive cells. Daratumumab has a favorable toxicity profile and encouraging clinical activity as a single agent and in combination with lenalidomide in heavily pretreated, relapsed patients in whom other novel agents (such as bortezomib, thalidomide and lenalidomide) and stem cell transplant have already failed...
October 2016: Drugs of Today
https://www.readbyqxmd.com/read/27910767/immunostimulatory-effects-of-melphalan-and-usefulness-in-adoptive-cell-therapy-with-antitumor-cd4-t-cells
#17
Michal Kuczma, Zhi-Chun Ding, Gang Zhou
The alkylating agent melphalan is used in the treatment of hematological malignancies, especially multiple myeloma. In the past, the usefulness of melphalan has been solely attributed to its cytotoxicity on fastgrowing cancerous cells. Although the immunomodulatory effects of melphalan were suggested many years ago, only recently has this aspect of melphalan's activity begun to be elucidated at the molecular level. Emerging evidence indicates that melphalan can foster an immunogenic microenvironment by inducing immunogenic cell death (ICD) as characterized by membrane translocation of endoplasmic reticulum protein calreticulin (CRT) and by release of chromatin-binding protein high-mobility group box 1 (HMGB1)...
2016: Critical Reviews in Immunology
https://www.readbyqxmd.com/read/27909306/rpl5-on-1p22-1-is-recurrently-deleted-in-multiple-myeloma-and-its-expression-is-linked-to-bortezomib-response
#18
I J F Hofman, M Van Duin, E De Bruyne, L Fancello, G Mulligan, E Geerdens, E Garelli, C Mancini, H Lemmens, M Delforge, P Vandenberghe, I Wlodarska, A Aspesi, L Michaux, K Vanderkerken, P Sonneveld, K De Keersmaecker
Chromosomal region 1p22 is deleted in ⩾20% of multiple myeloma (MM) patients, suggesting the presence of an unidentified tumor suppressor. Using high-resolution genomic profiling, we delimit a 58 kb minimal deleted region (MDR) on 1p22.1 encompassing two genes: ectopic viral integration site 5 (EVI5) and ribosomal protein L5 (RPL5). Low mRNA expression of EVI5 and RPL5 was associated with worse survival in diagnostic cases. Patients with 1p22 deletion had lower mRNA expression of EVI5 and RPL5, however, 1p22 deletion status is a bad predictor of RPL5 expression in some cases, suggesting that other mechanisms downregulate RPL5 expression...
December 2, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27907052/prevalence-and-mortality-related-factors-of-multiple-myeloma-in-taiwan
#19
Jia-Hong Chen, Chi-Hsiang Chung, Yung-Chih Wang, Shun-Neng Hsu, Wen-Yen Huang, Wu-Chien Chien
In this retrospective cohort study based in Taiwan, we reported the current epidemiology of patients with multiple myeloma and analyzed the factors affecting mortality. We identified 7285 patients with newly diagnosed multiple myeloma (MM) between 1997 and 2013 in Taiwan. Privileges data from the National Health Institute Research Database was used, as it is made readily available to the public in electronic format for research purposes. From 1997 to 2013, the average incidence of MM per 100,000 people was 1...
2016: PloS One
https://www.readbyqxmd.com/read/27905203/efficacy-and-toxicity-of-the-combination-chemotherapy-of-thalidomide-alkylating-agent-and-steroid-for-relapsed-refractory-myeloma-patients-a-report-from-the-korean-multiple-myeloma-working-party-kmmwp-retrospective-study
#20
Jihyun Kwon, Chang-Ki Min, Kihyun Kim, Jae-Joon Han, Joon Ho Moon, Hye Jin Kang, Hyeon-Seok Eom, Min Kyoung Kim, Hyo Jung Kim, Dok Hyun Yoon, Jeong-Ok Lee, Won Sik Lee, Jae Hoon Lee, Je-Jung Lee, Yoon-Seok Choi, Sung Hyun Kim, Sung-Soo Yoon
We analyzed the treatment responses, toxicities, and survival outcomes of patients with relapsed or refractory multiple myeloma who received daily thalidomide, cyclophosphamide, and dexamethasone (CTD) or daily thalidomide, melphalan, and prednisolone (MTP) at 17 medical centers in Korea. Three-hundred and seventy-six patients were enrolled. The combined chemotherapy of thalidomide, corticosteroid, and an alkylating agent (TAS) was second-line chemotherapy in 142 (37.8%) patients, and third-line chemotherapy in 135 (35...
December 1, 2016: Cancer Medicine
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