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Multiple myeloma, young patient

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https://www.readbyqxmd.com/read/29920189/oncogenic-trk-fusions-are-amenable-to-inhibition-in-hematologic-malignancies
#1
Justin Taylor, Dean Pavlick, Akihide Yoshimi, Christina Marcelus, Stephen S Chung, Jaclyn F Hechtman, Ryma Benayed, Emiliano Cocco, Benjamin H Durham, Lillian Bitner, Daichi Inoue, Young Rock Chung, Kerry Mullaney, Justin M Watts, Eli L Diamond, Lee A Albacker, Tariq I Mughal, Kevin Ebata, Brian B Tuch, Nora Ku, Maurizio Scaltriti, Mikhail Roshal, Maria Arcila, Siraj Ali, David M Hyman, Jae H Park, Omar Abdel-Wahab
Rearrangements involving the neurotrophic receptor kinase genes (NTRK1, NTRK2, and NTRK3; hereafter referred to as TRK) produce oncogenic fusions in a wide variety of cancers in adults and children. Although TRK fusions occur in <1% of all solid tumors, inhibition of TRK results in profound therapeutic responses resulting in breakthrough FDA-approval of the TRK inhibitor larotrectinib for adult and pediatric solid tumor patients regardless of histology. In contrast to solid tumors, the frequency of TRK fusions and clinical effects of targeting TRK in hematologic malignancies is unknown...
June 19, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29899820/pre-clinical-validation-of-b-cell-maturation-antigen-bcma-as-a-target-for-t-cell-immunotherapy-of-multiple-myeloma
#2
De-Xiu Bu, Reshma Singh, Eugene E Choi, Marco Ruella, Selene Nunez-Cruz, Keith G Mansfield, Paul Bennett, Nathanial Barton, Qilong Wu, Jiquan Zhang, Yongqiang Wang, Lai Wei, Shawn Cogan, Tucker Ezell, Shree Joshi, Kellie J Latimer, Brian Granda, William R Tschantz, Regina M Young, Heather A Huet, Celeste J Richardson, Michael C Milone
Multiple myeloma has a continued need for more effective and durable therapies. B cell maturation antigen (BCMA), a plasma cell surface antigen and member of the tumor necrosis factor (TNF) receptor superfamily, is an attractive target for immunotherapy of multiple myeloma due to its high prevalence on malignant plasma cells. The current work details the pre-clinical evaluation of BCMA expression and development of a chimeric antigen receptor (CAR) targeting this antigen using a fully human single chain variable fragment (scFv)...
May 25, 2018: Oncotarget
https://www.readbyqxmd.com/read/29794540/closing-knowledge-gaps-to-optimize-patient-outcomes-and-advance-precision-medicine
#3
Kathy Giusti, Anne Quinn Young, Kerri Lehrhaupt
Realizing the promise of precision medicine requires patient engagement at the key decision points throughout the cancer journey. Previous research has shown that patients who make the "right" decisions, such as being treated at a high-volume academic medical center, for example, have better outcomes. An online survey was conducted to understand awareness of and barriers to these decision points among patients with multiple myeloma and pancreatic, lung, prostate, and metastatic breast cancers. Survey respondents were identified by 5 participating foundations (multiple myeloma: n = 86, pancreatic: n = 108, lung: n = 56, prostate: n = 50, metastatic breast: n = 86) and recruited by an e-mail or social media invitation...
May 2018: Cancer Journal
https://www.readbyqxmd.com/read/29746513/role-of-18f-fdg-pet-ct-in-patients-without-known-primary-malignancy-with-skeletal-lesions-suspicious-for-cancer-metastasis
#4
Soo Bin Park, Jung Mi Park, Seung Hwan Moon, Young Seok Cho, Jong-Mu Sun, Byung-Tae Kim, Kyung-Han Lee
BACKGROUND: When subjects without a known malignancy present with suspicious skeletal lesions, differential diagnosis and primary cancer identification is important. Here, we investigated the role of FDG PET/CT in this clinical situation. METHODS: We enrolled 103 patients with no known malignancies who were referred for FDG PET/CT because of bone lesions that were suspicious for cancer metastasis. Each extra-skeletal FDG lesion was categorized as consistent with primary cancer or with metastasis based on the distribution and pattern of all abnormal lesions in the individual...
2018: PloS One
https://www.readbyqxmd.com/read/29713226/prognostic-value-of-baseline-18-f-fluorodeoxyglucose-pet-ct-in-patients-with-multiple-myeloma-a-multicenter-cohort-study
#5
Seung Hwan Moon, Woo Hee Choi, Ie Ryung Yoo, Soo Jin Lee, Jin Chul Paeng, Shin Young Jeong, Sang-Woo Lee, Kihyun Kim, Joon Young Choi
Objective: We investigated the prognostic value of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG PET/CT) in patients with multiple myeloma (MM). Materials and Methods: Subjects were 76 patients with newly diagnosed myeloma and pretreatment with 18 F-FDG PET/CT from four hospitals. The PET/CT features were evaluated and the clinical characteristics were reviewed. Prognostic factors related to poor progression-free survival (PFS) and overall survival (OS) were identified using a Cox proportional hazards regression model and a prediction scale was developed based on the identified factors...
May 2018: Korean Journal of Radiology: Official Journal of the Korean Radiological Society
https://www.readbyqxmd.com/read/29706650/innovative-strategies-minimize-engraftment-syndrome-in-multiple-myeloma-patients-with-novel-induction-therapy-following-autologous-hematopoietic-stem-cell-transplantation
#6
Gonzalo Gutiérrez-García, Montserrat Rovira, Laura Magnano, Laura Rosiñol, Alex Bataller, María Suárez-Lledó, María Teresa Cibeira, Carlos Fernández de Larrea, Marta Garrote, Sofia Jorge, Ana Moreno, Luis Gerardo Rodríguez-Lobato, Enric Carreras, Maribel Díaz-Ricart, Marta Palomo, Carmen Martínez, Alvaro Urbano-Ispizua, Joan Bladé, Francesc Fernández-Avilés
Autologous stem cell transplantation (PBSCT) is standard for young patients in MM and its TRM has decreased after the 2000s. Bortezomib and immunomodulatory agents (IMiDs) in MM have improved the outcome. However, they seem to boost pro-inflammatory stage increasing the incidence of engraftment syndrome (ES). Favorable factors in PBSCT such as G-CSF could increase inflammatory stage during transplant. Corticosteroids have shown an excellent response of ES and some authors propose them as prophylaxis for ES...
April 29, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29661776/targeting-the-leukemia-antigen-pr1-with-immunotherapy-for-the-treatment-of-multiple-myeloma
#7
Gheath Alatrash, Alexander A Perakis, Celine Kerros, Haley L Peters, Pariya Sukhumalchandra, Mao Zhang, Haroon Jakher, Madhushree Zope, Rebecca Patenia, Anna Sergeeva, Shuhua Yi, Ken H Young, Anne V Philips, Amanda M Cernosek, Haven R Garber, Na Qiao, Jinsheng Weng, Lisa S St John, Sijie Lu, Karen Clise-Dwyer, Elizabeth A Mittendorf, Qing Ma, Jeffrey J Molldrem
Purpose: PR1 is a human leukocyte antigen (HLA)-A2 nonameric peptide derived from neutrophil elastase (NE) and proteinase 3 (P3). We have previously shown that PR1 is cross-presented by solid tumors, leukemia, and antigen-presenting cells, including B cells. We have also shown that cross-presentation of PR1 by solid tumors renders them susceptible to killing by PR1-targeting immunotherapies. As multiple myeloma is derived from B cells, we investigated whether multiple myeloma is also capable of PR1 cross-presentation and subsequently capable of being targeted by using PR1 immunotherapies...
April 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29616647/epidemiology-of-malignant-hemopathies-recorded-in-hospitals-in-cameroon
#8
P T Moueleu Ngalagou, E Ngouadjeu Dongho Tsakeu, F Ngo Sack, E C Eboumbou Moukoko, Y Konn Jolly, H Luma
Data about malignant blood diseases are sparse in Cameroon. Their epidemiology was studied in patients at the General Hospital of Douala (GHD) and the Yaoundé Central Hospital (CHY) from 2004 through 2014. The variables we studied were social and demographic (age, sex, occupation, marital status), clinical (reasons for consultation, clinical signs, year of diagnosis), and biological (blood count, myelogram and blood smear, immunophenotyping, biopsy, and cytogenetics). In all, 4409 files were reviewed and 454 cases identified, documented and confirmed (248 in GHD and 206 in CHY)...
February 1, 2018: Médecine et Santé Tropicales
https://www.readbyqxmd.com/read/29555314/the-role-of-allogeneic-transplantation-for-multiple-myeloma-in-the-era-of-novel-agents-a-study-from-the-japanese-society-of-myeloma
#9
Koji Kawamura, Nobuhiro Tsukada, Yoshinobu Kanda, Takashi Ikeda, Akiyo Yoshida, Yasunori Ueda, Tadao Ishida, Kenshi Suzuki, Hirokazu Murakami
Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered a potentially curative therapy for patients with multiple myeloma, the role of allo-HSCT remains unclear in the novel agent era. We conducted a retrospective study of 65 patients with multiple myeloma who underwent allo-HSCT at 19 institutions from 2009 to 2016. Patients received a median of 3 (range, 1 to 7) lines of prior therapy, including at least 1 novel agent, except for autologous HSCT. The 3-year progression-free survival (PFS) and overall survival (OS) rates were 18...
March 16, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29531285/defining-cure-in-multiple-myeloma-a-comparative-study-of-outcomes-of-young-individuals-with-myeloma-and-curable-hematologic-malignancies
#10
Praful Ravi, Shaji K Kumar, James R Cerhan, Matthew J Maurer, David Dingli, Stephen M Ansell, S Vincent Rajkumar
Advances in therapy in recent years have led investigators to challenge the dogma that multiple myeloma (MM) is incurable. We assessed overall (OS) and progression-free survival (PFS) of young patients ( ≤ 50 years) with MM and compared outcomes with follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and Hodgkin lymphoma (HL). All patients ≤ 50 years with newly diagnosed MM (n = 212), FL (n = 168), DLBCL (n = 195), and HL (n = 233) between 1 January 2005 and 31 December 2015 were included...
February 28, 2018: Blood Cancer Journal
https://www.readbyqxmd.com/read/29518205/the-combination-of-ionizing-radiation-and-proteasomal-inhibition-by-bortezomib-enhances-the-expression-of-nkg2d-ligands-in-multiple-myeloma-cells
#11
Young Shin Lee, Woong Heo, Jiho Nam, Young Hwa Jeung, Jaeho Bae
Bortezomib, which is a potent proteasome inhibitor, has been used as a first-line drugs to treat multiple myeloma for a few decades, and radiotherapy has frequently been applied to manage acute bone lesions in the patients. Therefore, it was necessary to investigate what the benefits might be if the two therapies were applied simultaneously in the treatment of multiple myeloma. Since it was known that radiotherapy and proteasome inhibitors could increase the expression of NKG2D ligands through induction of protein synthesis and suppression of protein degradation of NKG2D ligands, respectively, we supposed that the combined treatment might further enhance the expression of NKG2D ligands...
March 6, 2018: Journal of Radiation Research
https://www.readbyqxmd.com/read/29511683/circulating-cd3-cd4-cd161-cells-are-associated-with-early-complications-after-autologous-stem-cell-transplantation-in-multiple-myeloma
#12
Sung-Eun Lee, Ji-Young Lim, Da-Bin Ryu, Tae Woo Kim, Young-Woo Jeon, Jae-Ho Yoon, Byung-Sik Cho, Ki-Seong Eom, Yoo-Jin Kim, Hee-Je Kim, Seok Lee, Seok-Goo Cho, Dong-Wook Kim, Jong Wook Lee, Woo-Sung Min, Chang-Ki Min
The aim of this study was to explore if measurement of pretransplant circulating CD161-expressing cells, in addition to clinical risk factors, could predict mucositis and infections in patients with multiple myeloma (MM) undergoing autologous stem cell transplantation (ASCT). To determine if CD161-expressing cells are likely to predict early complications, namely, mucositis (≥grade 3), infections, and cytomegalovirus (CMV) reactivation, we prospectively examined CD161-expressing cells (CD3+ CD4+ CD161+ and CD3+ CD8+ CD161+ ) in peripheral blood samples from 108 patients with MM undergoing ASCT...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29414597/young-female-patients-with-multiple-myeloma-have-low-occurrence-of-osteolytic-lesion
#13
Danfeng Zhang, Jingcao Huang, Wenyan Zhang, Ling Pan, Dan Zhang, Pan Zhao, Fangfang Wang, Hongmei Luo, Jin He, Yu Qin, Ying Qu, Tingting Guo, Ting Niu, Yuhuan Zheng
OBJECTIVE: Osteolytic lesion (OL) and bone damage are common complications in multiple myeloma (MM). This study aimed to analyze the occurrence of OL in MM patient groups of different ages and genders. PATIENTS AND METHODS: We performed a retrospective study of 762 MM patients admitted to West China Hospital from 2009 to 2014 to investigate the association between OL occurrence with patients' ages and genders. The presence or absence of OL was confirmed by X-ray, computed tomography (CT) or magnetic resonance imaging (MRI) examination...
May 2018: Bone
https://www.readbyqxmd.com/read/29339269/phase-2-study-of-an-intravenous-busulfan-and-melphalan-conditioning-regimen-for-autologous-stem-cell-transplantation-in-patients-with-multiple-myeloma-kmm150
#14
Sung-Hoon Jung, Je-Jung Lee, Jin Seok Kim, Chang-Ki Min, Kihyun Kim, Yunsuk Choi, Hyeon-Seok Eom, Young Don Joo, Sung-Hyun Kim, Jae-Yong Kwak, Hye Jin Kang, Jae Hoon Lee, Ho Sup Lee, Yeung-Chul Mun, Joon Ho Moon, Sang Kyun Sohn, Seong Kyu Park, Yong Park, Ho-Jin Shin, Sung-Soo Yoon
This prospective study evaluated the efficacy and toxicity of intravenous busulfan and melphalan as a conditioning regimen for autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM). A total of 99 patients with MM, enrolled between January 2013 and March 2016, received intravenous busulfan (9.6 mg/kg) and melphalan (140 mg/m2 ) before ASCT. The median time to transplant was 6.2 months, and 90 (90.9%) patients underwent ASCT within 12 months of the diagnosis. The overall response rate after ASCT was 94...
May 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29326807/heavy-chain-diseases-and-myeloma-associated-fanconi-syndrome-an-update
#15
REVIEW
Roberto Ria, Franco Dammacco, Angelo Vacca
The heavy chain diseases (HCDs) are rare B-cell malignancies characterized by the production of a monoclonal immunoglobulin heavy chain without an associated light chain. There are three types of HCD, defined by the class of immunoglobulin heavy chain produced: IgA (α-HCD), IgG (γ-HCD), and IgM (μ-HCD). Alpha-HCD is the most common and usually occurs as intestinal malabsorption in a young adult from a country of the Mediterranean area. Gamma- and μ-HCDs are rarer and associated with a B-cell non-Hodgkin lymphoma that produces an abnormal Ig heavy chain...
2018: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/29301755/copper-64-labeled-daratumumab-as-a-pet-ct-imaging-tracer-for-multiple-myeloma
#16
Enrico Caserta, Junie Chea, Megan Minnix, Domenico Viola, Steven Vonderfecht, Paul Yazaki, Desiree Crow, Jihane Khalife, James F Sanchez, Joycelynne M Palmer, Susanta Hui, Nadia Carlesso, Jonathan Keats, Young Kim, Ralf Buettner, Guido Marcucci, Steven Rosen, John Shively, David Colcher, Amrita Krishnan, Flavia Pichiorri
As a growing number of patients with multiple myeloma (MM) respond to upfront therapies while eventually relapsing in a time frame that is often unpredictable, attention has increasingly focused on developing novel diagnostic criteria to also account for disease dissemination. Positron emission tomography/computed tomography (PET/CT) is often used as a noninvasive monitoring strategy to assess cancer cell dissemination, but because the uptake of the currently used radiotracer 18fluorodeoxyglucose (18 F-FDG) is a function of the metabolic activity of both malignant and nonmalignant cells, the results frequently lack sufficient specificity...
February 15, 2018: Blood
https://www.readbyqxmd.com/read/29259965/clinical-characteristics-causes-and-survival-in-115-cancer-patients-with-parathyroid-hormone-related-protein-mediated-hypercalcemia
#17
Joon Jin, Jin Ook Chung, Min Young Chung, Dong Hyeok Cho, Dong Jin Chung
Background: The aim of this study is to determine the proportion of cancers presenting with parathyroid hormone (PTH) related protein (PTHrP)-mediated hypercalcemia, examine the clinical and biochemical characteristics, identify predictive factors for survival. And we also compared those characteristics between solid organ and hematologic malignancy groups. Methods: Cancer patients with PTHrP-mediated hypercalcemia who were treated at Chonnam National University Hospital in Korea from January 2005 to January 2015 were retrospectively reviewed...
November 2017: Journal of Bone Metabolism
https://www.readbyqxmd.com/read/29244706/streptococcus-pneumoniae-osteomyelitis-in-a-25-year-old-man-as-the-initial-presentation-of-multiple-myeloma-a-case-report
#18
Tracy Webber, Michael Lawlor, Tessa Balach
CASE: We report the case of a 25-year-old man with femoral Streptococcus pneumoniae pyomyositis as well as hypercalcemia, mild anemia, and elevated inflammatory markers; he subsequently was diagnosed with immunoglobulin G (IgG) kappa multiple myeloma. CONCLUSION: Multiple myeloma most commonly affects patients who are >60 years of age, and causes clinical symptoms from anemia, lytic bone lesions, hypercalcemia, and renal failure. These findings and a monoclonal protein spike serve as initial diagnostic and treatment criteria...
July 2017: JBJS Case Connector
https://www.readbyqxmd.com/read/29222298/management-of-multiple-myeloma-in-the-newly-diagnosed-patient
#19
REVIEW
María-Victoria Mateos, Jesús F San Miguel
Multiple myeloma is the second most frequent hematological disease. The introduction of melphalan as high-dose therapy followed by autologous hematopoietic cell transplantation (HDT/ASCT) for young patients and the availability of novel agents for young and elderly patients with multiple myeloma have dramatically changed the perspective of treatment. However, further research is necessary if we want definitively to cure the disease. Treatment goals for transplant-eligible and non-transplant-eligible patients should be to prolong survival by achieving the best possible response while ensuring quality of life...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222258/fixed-duration-vs-continuous-therapy-in-multiple-myeloma
#20
REVIEW
Heinz Ludwig, Niklas Zojer
The introduction of new drugs with less severe toxicity profiles than those of conventional antimyeloma agents allowed the evaluation of continuous therapy compared with fixed duration therapy. In transplant-eligible patients, consolidation therapy with bortezomib or bortezomib-based regimens showed significant progression-free survival (PFS) benefit in cytogenetic standard-risk patients and to a lesser extent, high-risk patients. Continuous therapy with lenalidomide maintenance treatment after autologous stem cell transplantation resulted in a significant survival gain...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
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