Tamir Shragai, Moshe E Gatt, Adir Shaulov, Eirini Katodritou, Theodora Triantafyllou, Noa Lavi, Anastasia Pouli, Anastasia Sioni, Iuliana Vaxman, Miri Zektser, Chezi Ganzel, Noam Benyamini, Svetlana Trestman, Tomer Ziv-Baran, Yasmin Adam, Yael C Cohen, Irit Avivi
BACKGROUND: Multiple myeloma (MM) patients presenting with anaemia as their sole clinical manifestation are rare and not fully defined. METHODS: Retrospective multi-site study comparing the characteristics and outcome of MM patients with anaemia only with matched patients, presenting with multi-organ disease. RESULTS: Anaemia-only patients had a higher percentage of bone marrow monoclonal plasma cells group (median 60% [IQR 42-80%] vs. 37% [IQR 17-65%], respectively; p < 0...
December 31, 2020: Leukemia Research
Elifcan Aladag, Sude Hatun Aktimur, Öznur Aydın, Haluk Demiroglu, Yahya Buyukasik, Salih Aksu, Osman Ilhami Ozcebe, Ibrahim Celalettin Haznedaroglu, Nilgun Sayinalp, Mehmet Turgut, Hakan Goker
INTRODUCTION: Acute lymphoblastic leukemia (ALL) is a malign disease with poor prognosis in adults. After remission is achieved by induction therapy, administration of allogeneic hematopoietic stem-cell transplantation (AHSCT) is one of the standard treatment in adult ALL patients. Pediatric-inspired chemotherapy has been demonstrated to improve outcomes of adult ALL. The aim of this study was to compare the Berlin-Frankfurt-Münster-95 chemotherapy (BFM-95) regimen and AHSCT results in ALL patients with first complete remission...
January 12, 2021: Clinical Lymphoma, Myeloma & Leukemia
Jiri Minarik, Tomas Pika, Jakub Radocha, Alexandra Jungova, Jan Straub, Tomas Jelinek, Ludek Pour, Petr Pavlicek, Martin Mistrik, Lucie Brozova, Petra Krhovska, Katerina Machalkova, Pavel Jindra, Ivan Spicka, Hana Plonkova, Martin Stork, Jaroslav Bacovsky, Lenka Capkova, Michal Sykora, Petr Kessler, Lukas Stejskal, Adriana Heindorfer, Jana Ullrychova, Tomas Skacel, Vladimir Maisnar, Roman Hajek
BACKGROUND: We have performed a head to head comparison of all-oral triplet combination of ixazomib, lenalidomide and dexamethasone (IRD) versus lenalidomide and dexamethasone (RD) in patients with relapsed and refractory multiple myeloma (RRMM) in the routine clinical practice. METHODS: A total of 344 patients treated with IRD (N = 127) or RD (N = 217) were selected for analysis from the Czech Registry of Monoclonal Gammopathies (RMG). Descriptive statistics were used to assess patient's characteristics associated with the respective therapy...
January 15, 2021: BMC Cancer
Mariko Ishibashi, Rimpei Morita, Hideto Tamura
The signaling lymphocytic activation molecule (SLAM) family receptors are expressed on various immune cells and malignant plasma cells in multiple myeloma (MM) patients. In immune cells, most SLAM family molecules bind to themselves to transmit co-stimulatory signals through the recruiting adaptor proteins SLAM-associated protein (SAP) or Ewing's sarcoma-associated transcript 2 (EAT-2), which target immunoreceptor tyrosine-based switch motifs in the cytoplasmic regions of the receptors. Notably, SLAMF2, SLAMF3, SLAMF6, and SLAMF7 are strongly and constitutively expressed on MM cells that do not express the adaptor proteins SAP and EAT-2...
January 13, 2021: Cancers
Jifang Zhou, Karen Sweiss, Edith A Nutescu, Jin Han, Pritesh R Patel, Naomi Y Ko, Todd A Lee, Brian C-H Chiu, Gregory S Calip
PURPOSE: Intravenous (IV) bisphosphonates reduce the risk of skeletal-related events in patients with multiple myeloma (MM). However, data describing racial differences in IV bisphosphonate utilization outside of clinical trial settings are limited. We evaluated population-level IV bisphosphonate initiation and discontinuation among patients of age ≥ 65 years with MM. METHODS: We conducted a retrospective cohort study of patients of age ≥ 65 years diagnosed with first primary MM between 2001 and 2011...
January 15, 2021: JCO oncology practice
Youmei Zi, Yingzi Zhang, Yanwei Wu, Lina Zhang, Ru Yang, Yan Huang
Numerous studies have confirmed that microRNAs (miRNAs or miRs) have important roles in cancer biogenesis and development including multiple myeloma (MM). MicroRNA‑25‑3p (miR‑25‑3p) has been proven to promote cancer progression, whereas its functions in MM has not yet been reported, at least to the best of our knowledge. Therefore, the present study aimed to investigate the function of miR‑25‑3p in MM and to identify the potential underlying mechanistic pathway. Herein, it was found that miR‑25‑3p expression was significantly increased in MM tissues and cell lines...
March 2021: International Journal of Molecular Medicine
Ji Hyun Lee, Yong Park, Ka-Won Kang, Je-Jung Lee, Ho Sup Lee, Hyeon-Seok Eom, Young Rok Do, Jin Seok Kim, Sung-Soo Yoon, Dong-Yeop Shin, Youngil Koh, Ki-Hyun Kim, Won Sik Lee, Jae-Cheol Jo, Yoo Jin Lee, Ji Yun Lee, Dae Sik Kim, Hyeok Shim, Myung Hee Chang, Sung-Hyun Kim, Chang-Ki Min
Carfilzomib, lenalidomide, and dexamethasone (KRd) effectively improve survival in patients with relapsed and refractory multiple myeloma (RRMM). However, the outcome of KRd treatment in Asian patients reflecting a general RRMM population outside of a clinical trial has not been reported. Fifty-five RRMM patients who were treated with carfilzomib in combination with Rd from the time of the first approval of KRd in the Republic of Korea were analyzed. The median age was 61 years. The percentage of patients with an ECOG performance status ≥ 3, creatinine clearance < 50 mL/min, high-risk cytogenetics, and ≥ 4 lines of prior treatment were 9%, 22%, 31%, and 27%, respectively...
January 15, 2021: Annals of Hematology
Ichiro Hanamura
Multiple myeloma (MM), a plasma cell neoplasm, is an incurable hematological malignancy characterized by complex genetic and prognostic heterogeneity. Gain or amplification of chromosome arm 1q21 (1q21+) is the most frequent adverse chromosomal aberration in MM, occurring in 40% of patients at diagnosis. It occurs in a subclone of the tumor as a secondary genomic event and is more amplified as the tumor progresses and a risk factor for the progression from smoldering multiple myeloma to MM. It can be divided into either 1q21 gain (3 copies) or 1q21 amplification (≥4 copies), and it has been suggested that the prognosis is worse in cases of amplification than gain...
January 12, 2021: Cancers
Sarah Gooding, Naser Ansari-Pour, Fadi Towfic, María Ortiz Estévez, Philip P Chamberlain, Kao-Tai Tsai, Erin Flynt, Marissa Hirst, Dan Rozelle, Paula Dhiman, Paola Neri, Karthik Ramasamy, Nizar Bahlis, Paresh Vyas, Anjan Thakurta
Emergence of drug resistance to all available therapies is the major challenge to improving survival in myeloma. Cereblon (CRBN) is the essential binding protein of the widely used immunomodulatory drugs (IMiDs) and novel CRBN E3 ligase modulator drugs (CELMoDs) in myeloma, as well as certain proteolysis targeting chimeras (PROTACs), in development for a range of diseases. Using whole-genome sequencing (WGS) data from 455 patients and RNA sequencing (RNASeq) data from 655 patients, including newly diagnosed (WGS, n = 198; RNASeq, n = 437), lenalidomide (LEN)-refractory (WGS, n = 203; RNASeq, n = 176), and pomalidomide (POM)-refractory cohorts (WGS, n = 54; RNASeq, n = 42), we found incremental increases in the frequency of 3 CRBN aberrations, namely point mutations, copy losses/structural variations, and a specific variant transcript (exon 10 spliced), with progressive IMiD exposure, until almost one-third of patients had CBRN alterations by the time they were POM refractory...
January 14, 2021: Blood
Elizabeth B Lamont, Andrew J Yee, Stuart L Goldberg, David S Siegel, Andrew D Norden
Genomic biomarkers inform treatment in multiple myeloma (MM), making patient clinical data a potential window into MM biology. We evaluated de novo MM patients for associations between specific MM cytogenetic patterns and prior cancer history. Analyzing a MM real-world dataset, we identified a cohort of 1769 patients with fluorescent in situ hybridization cytogenetic testing at diagnosis. Of the patients, 241 (0.14) had histories of prior cancer(s). Amplification of the long arm of chromosome 1 [amp(1q)] varied by prior cancer history (0...
February 2021: JNCI Cancer Spectrum
Lauren Suarez, Ruipeng Wang, Scott Carmer, Daniel Bednarik, Han Myint, Kristi Jones, Mathias Oelke
Over the last decade, tremendous progress has been made in the field of adoptive cell therapy. The two prevailing modalities include endogenous non-engineered approaches and genetically engineered T-cell approaches. Endogenous non-engineered approaches include dendritic cell-based systems and tumor-infiltrating lymphocytes (TIL) that are used to produce multi-antigen-specific T-cell products. Genetically engineered approaches, such as T-cell receptor engineered cells and chimeric antigen receptor T cells are used to produce single antigen-specific T-cell products...
December 2020: Transfusion Medicine and Hemotherapy
Yanfang Liu, Chao-Hsiun Tang, Hong Qiu, Sarah Siggins, Hsin-An Hou
Limited real-world data are available regarding treatment practices and outcomes of multiple myeloma (MM) in Asia. We conducted a retrospective cohort study using the Taiwan National Healthcare Insurance Research database and Taiwan Death Registry and used a Markov model to describe disease progression and outcomes in 4092 patients newly diagnosed with MM from 01-Jan-2007 to 31-Dec-2015. We observed marked differences in the characteristics, length and outcome of the clinical journey between patients who did/did not receive autologous stem cell transplant, and between patients initiated on novel agents versus other treatment regimens...
January 13, 2021: Scientific Reports
Martina Recalde, Veronica Davila-Batista, Yesika Díaz, Michael Leitzmann, Isabelle Romieu, Heinz Freisling, Talita Duarte-Salles
BACKGROUND: A high body mass index (BMI) has been associated with increased risk of several cancers; however, whether BMI is related to a larger number of cancers than currently recognized is unclear. Moreover, whether waist circumference (WC) is more strongly associated with specific cancers than BMI is not well established. We aimed to investigate the associations between BMI and 26 cancers accounting for non-linearity and residual confounding by smoking status as well as to compare cancer risk estimates between BMI and WC...
January 14, 2021: BMC Medicine
Weimei Jin, Xiaoli Wang, Yuxiao Zeng, Yifen Lan, Xiaoqiu Wang
Multiple myeloma (MM) is incurable cancer in the blood system. Magnolol is an effective component against various cancers. This study tried to investigate the effect and mechanism of magnolol on MM via regulating miR-129. Human normal plasma cells (nPCs) and MM cells U266 and LP1 were used in this study, accompanied by treatment of magnolol. The miR-129 inhibitor was transfected into U266 and LP1 cells during experiments. Cell viability was detected by Cell Counting Kit-8 assay. Cell migration and invasion were tested by wound healing assay and Transwell assay...
January 14, 2021: Neoplasma
Michelle Kinder, Nizar J Bahlis, Fabio Malavasi, Bart De Goeij, Alexander Babich, Jocelyn Sendecki, Joshua Rusbuldt, Kevin Bellew, Colleen Kane, Niels W C J Van de Donk
Not available.
January 14, 2021: Haematologica
Frank Bridoux, Nelson Leung, Mohamed Belmouaz, Virginie Royal, Pierre Ronco, Samih H Nasr, Jean Paul Fermand
Symptomatic multiple myeloma (MM) is commonly complicated by acute kidney injury (AKI), through various mechanisms. The most frequent is the precipitation of monoclonal free light chains (FLC) with uromodulin in the distal tubules, defining light chain cast nephropathy (LCCN). Early diagnosis and identification of the cause of AKI are required for optimizing management and avoiding chronic kidney injury that strongly affects quality of life and patient survival. In LCCN, often manifesting with severe AKI, renal recovery requires urgent intervention based on vigorous rehydration, correction of precipitating factors and efficient anti-plasma cell chemotherapy to rapidly reduce the secretion of nephrotoxic FLC...
January 10, 2021: Kidney International
Mayako Uchida, Takehiro Kawashiri, Nami Maegawa, Aoi Takano, Keiko Hosohata, Yoshihiro Uesawa
PURPOSE: Bendamustine is used in hematologic malignancies such as non-Hodgkin lymphoma, chronic lymphocytic leukemia, and multiple myeloma. This study evaluated the association of bendamustine-related skin disorders using the Japanese Adverse Drug Event Report (JADER) database. METHODS: We identified and analyzed reports of skin disorders between April 2004 and November 2019 from the JADER database and calculated the reported odds ratios (RORs) using disproportionality analysis...
2021: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
Meng Liu, Jin Jin, Yanjie Ji, Huizhuang Shan, Zhihui Zou, Yang Cao, Li Yang, Ligen Liu, Li Zhou, Hu Lei, Yunzhao Wu, Hanzhang Xu, Yingli Wu
The stability of Ikaros family zinc finger protein 1 (Ikaros), a critical hematopoietic transcription factor, can be regulated by cereblon (CRBN) ubiquitin ligase stimulated by immunomodulatory drugs in multiple myeloma. However, other stabilization mechanisms of Ikaros have yet to be elucidated. In this study, we show that the pharmacologic inhibition or knockdown of Hsp90 downregulates Ikaros in acute myeloid leukemia (AML) cells. Proteasome inhibitor MG132 but not autophagy inhibitor chloroquine could suppress the Hsp90 inhibitor STA-9090-induced reduction of Ikaros, which is accompanied with the increased ubiquitination of Ikaros...
January 8, 2021: Science China. Life Sciences
Vassilis Koutoulidis, Evangelos Terpos, Ioanna Klapa, George Cheliotis, Ioannis Ntanasis-Stathopoulos, Andriani Boultadaki, Maria Gavriatopoulou, Efstathios Kastritis, Meletios A Dimopoulos, Lia A Moulopoulos
OBJECTIVE. The purpose of this article is to analyze whole-body low-dose CT-detected appendicular medullary patterns of attenuation in patients with newly diagnosed multiple myeloma and to determine the diagnostic performance of whole-body low-dose CT in detecting diffuse marrow infiltration. MATERIALS AND METHODS. A total of 76 patients with myeloma who underwent whole-body low-dose CT and spinal MRI at initial assessment were retrospectively analyzed. The medullary cavities of femurs and humeri were evaluated qualitatively and quantitatively on CT...
January 13, 2021: AJR. American Journal of Roentgenology
Felasfa M Wodajo
This chapter is largely drawn from the recently published (2019) clinical practice guideline on the treatment of metastatic carcinoma and myeloma of the femur jointly produced by the Musculoskeletal Tumor Society, American Society for Radiation Oncology, and American Society of Clinical Oncology. Previous clinical practice guidelines on this topic broadly addressed the potential benefits of bone-targeted agents (eg, diphosphonates) on skeletal-related events, a broad term that encompasses pathologic fractures of any bone, need for surgery or radiation, and hypercalcemia...
2021: Instructional Course Lectures
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