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Allogeneic transplant in myeloma

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https://www.readbyqxmd.com/read/27913524/cellular-and-vaccine-immunotherapy-for-multiple-myeloma
#1
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/27913520/myeloma-management-of-the-newly-diagnosed-high-risk-patient
#2
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/27894207/when-to-recommend-a-second-autograft-in-patients-with-relapsed-myeloma
#3
Dimitrios C Ziogas, Evangelos Terpos, Meletios A Dimopoulos
In the current evolving landscape of myeloma therapies, no recommended salvage strategy exists for patients with relapsed multiple myeloma (MM) after initial successful autologous stem cell transplantation (ASCT) and therapeutic options extend from conventional chemotherapy and novel agents to second autologous and allogeneic transplants. In this article, we summarize the documented evidence about the utilization of second ASCT in patients with relapsed MM after a primary auto-graft and discuss the correct timing for such a salvage approach, the individual characteristics of patients who will benefit more, as well as the therapeutic role of second ASCT in the modern era of forthcoming anti-myeloma treatments...
November 28, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27825469/the-role-of-stem-cell-transplantation-in-waldenstrom-s-macroglobulinemia
#4
REVIEW
Rajshekhar Chakraborty, Eli Muchtar, Morie A Gertz
Waldenstrom's macroglobulinemia (WM) is an indolent B-cell lymphoma, which is highly chemosensitive, with an overall response rate over 90% to novel agents. However, most patients eventually relapse after response to first-line chemotherapy, necessitating further treatment. The possibility of long-lasting remission after high-dose cytotoxic chemotherapy followed by stem cell rescue is high in WM due to the chemosensitive nature of the disease and lower proliferative activity compared to multiple myeloma. In this paper, we have reviewed current evidence on autologous (auto-) and allogeneic (allo-) stem cell transplantation (SCT) in WM...
June 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27819687/impact-of-drug-development-on-the-use-of-stem-cell-transplantation-a-report-by-the-european-society-for-blood-and-marrow-transplantation-ebmt
#5
J R Passweg, H Baldomero, P Bader, C Bonini, S Cesaro, P Dreger, R F Duarte, C Dufour, J Kuball, D Farge-Bancel, A Gennery, N Kröger, F Lanza, A Nagler, A Sureda, M Mohty
Hematopoietic stem cell transplantation (HSCT) is used with increasing frequency in Europe with 40 000 transplants reported in 2014. Transplant-related mortality remains high in allogeneic HSCT (10-20%); high-dose chemotherapy is toxic and demanding for patients. Drug development is accelerating and with limited toxicity of some targeted drugs may replace HSCT, whereas others may function as a 'bridge to transplant'. We analyzed HSCT reported to the activity survey for selected diseases in which major advances in drug development have been made...
November 7, 2016: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/27759436/primary-plasma-cell-leukemia-2-0-advances-in-biology-and-clinical-management
#6
Antonino Neri, Katia Todoerti, Marta Lionetti, Vittorio Simeon, Marzia Barbieri, Filomena Nozza, Gabriella Vona, Alessandra Pompa, Luca Baldini, Pellegrino Musto
Primary plasma cell leukemia (PPCL) is a rare and aggressive variant of multiple myeloma. The introduction of novel agents and modern technologies has recently partially changed the clinical and biological scenario of this malignancy, allowing limited, but not negligible, progresses. Areas covered: We will discuss the complex landscape of genetic alterations in PPCL, derived from conventional and high-throughput technologies; the best available treatments for PPCL; the possible future therapeutic perspectives...
October 19, 2016: Expert Review of Hematology
https://www.readbyqxmd.com/read/27696266/transplantation-for-multiple-myeloma
#7
Yogesh S Jethava, Frits van Rhee
Multiple myeloma is a disorder characterized by accumulation of malignant plasma cells in the bone marrow, hypercalcemia, monoclonal protein, and end organ damage. Recently newer generation proteosome inhibitors, monoclonal antibodies and novel agents have been approved by FDA, which is undoubtedly increasing life expectancy of the patients. However, hematopoietic stem cell transplantation still remains the cornerstone of the treatment. In this chapter, we are discussing the autologous stem cell transplant, allogeneic stem cell transplant and total therapy trials with outcomes...
2016: Cancer Treatment and Research
https://www.readbyqxmd.com/read/27688610/newly-established-stem-cell-transplant-program-100-days-follow-up-of-patients-and-its-comparison-with-published-indian-literature
#8
Aseem Kumar Tiwari, Dinesh Arora, Ravi C Dara, Pranav Dorwal, Nitin Sood, Ruchira Misra, Sunil Kumar Gupta, Vimarsh Raina, Ashok Kumar Vaid
BACKGROUND: Hematopoietic progenitor stem cell transplantation (HPSCT) is used as a standard treatment option to improve outcome in hematological and nonhematological disorders. It is important for new HPSCT program to look at its patient outcome data and compare it with the published data to evaluate the efficacy of program. AIMS: The aim was to compile and collate the patient outcome data of HPSCT and compare with published reports. MATERIALS AND METHODS: Patient demographics, indications, stem cell harvest by apheresis, dose collected, infusion, engraftment, and follow-up data were collected from hospital information system from 2010 to 2013 in a tertiary care hospital...
July 2016: Indian Journal of Medical and Paediatric Oncology
https://www.readbyqxmd.com/read/27650125/treatment-options-for-relapse-after-autograft-in-multiple-myeloma-report-from-an-ebmt-educational-meeting
#9
Laurent Garderet, Gordon Cook, Holger W Auner, Benedetto Bruno, Henk Lokhorst, Jose Antonio Perez-Simon, Firoozeh Sahebi, Christof Scheid, Curly Morris, Anja van Biezen, Mohamad Sobh, Mauricette Michallet, Gösta Gahrton, Stefan Schönland, Nicolaus Kröger
Major improvements have been made in the treatment of myeloma. However, all patients, perhaps with some exceptions, eventually relapse, even after autologous stem cell transplantation (ASCT). In that setting, the combinations of new drugs, namely the IMiDs and the proteasome inhibitors along with steroids, give encouraging results in relapsed patients. The median progression-free survival (PFS) is 20 months with lenalidomide plus dexamethasone plus ixazomib and 26 months with lenalidomide plus dexamethasone plus carfilzomib...
September 21, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27646843/ricolinostat-plus-lenalidomide-and-dexamethasone-in-relapsed-or-refractory-multiple-myeloma-a-multicentre-phase-1b-trial
#10
Andrew J Yee, William I Bensinger, Jeffrey G Supko, Peter M Voorhees, Jesus G Berdeja, Paul G Richardson, Edward N Libby, Ellen E Wallace, Nicole E Birrer, Jill N Burke, David L Tamang, Min Yang, Simon S Jones, Catherine A Wheeler, Robert J Markelewicz, Noopur S Raje
BACKGROUND: Histone deacetylase (HDAC) inhibitors are an important new class of therapeutics for treating multiple myeloma. Ricolinostat (ACY-1215) is the first oral selective HDAC6 inhibitor with reduced class I HDAC activity to be studied clinically. Motivated by findings from preclinical studies showing potent synergistic activity with ricolinostat and lenalidomide, our goal was to assess the safety and preliminary activity of the combination of ricolinostat with lenalidomide and dexamethasone in relapsed or refractory multiple myeloma...
September 16, 2016: Lancet Oncology
https://www.readbyqxmd.com/read/27638367/chimeric-antigen-receptor-t-cells-and-hematopoietic-cell-transplantation-how-not-to-put-the-cart-before-the-horse
#11
Saad S Kenderian, David L Porter, Saar Gill
Hematopoietic cell transplantation (HCT) remains an important and potentially curative option for most hematologic malignancies. As a form of immunotherapy, allogeneic HCT (allo-HCT) offers the potential for durable remissions but is limited by transplantation- related morbidity and mortality owing to organ toxicity, infection, and graft-versus-host disease. The recent positive outcomes of chimeric antigen receptor T (CART) cell therapy in B cell malignancies may herald a paradigm shift in the management of these disorders and perhaps other hematologic malignancies as well...
September 13, 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27590108/allogeneic-hematopoietic-cell-transplantation-in-multiple-myeloma-focus-on-longitudinal-assessment-of-donor-chimerism-extramedullary-disease-and-high-risk-cytogenetic-features
#12
Leo Rasche, Christoph Röllig, Gernot Stuhler, Sophia Danhof, Stephan Mielke, Goetz Ulrich Grigoleit, Lea Dissen, Lea Schemmel, Jan Moritz Middeke, Viktoria Rücker, Martin Schreder, Johannes Schetelig, Martin Bornhäuser, Hermann Einsele, Christian Thiede, Stefan Knop
Although generally not applied as first-line treatment of multiple myeloma, allogeneic hematopoietic cell transplantation (allo-SCT) can still be chosen as ultimate escalation approach in high-risk patients, preferentially within the framework of clinical trials. In this study, we investigated whether decreasing donor chimerism (DC) is predictive for relapse. In addition, we comprehensively determined the impact of several other disease- and treatment-related factors on outcome. One hundred fifty-five multiple myeloma patients whose DC status was followed serially by the short tandem repeat-based techniques at a single lab were included in this retrospective study...
November 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27525143/a-case-of-undiagnosed-hiv-infection-in-a-57-year-old-woman-with-multiple-myeloma-consequences-on-chemotherapy-efficiency-and-safety
#13
I Poizot-Martin, S Brégigeon, C Tamalet, R Bouabdallah, O Zaegel-Faucher, V Obry-Roguet, A Ivanova, C E Cano, C Solas
Background. Non-AIDS-defining cancers represent a rising health issue among HIV-infected patients. Nevertheless, HIV testing is not systematic during the initial cancer staging. Here, we report a case of HIV infection diagnosed three years after chemotherapy initiation for multiple myeloma. Results. A 57-year-old woman diagnosed with multiple myeloma underwent a first round of chemotherapy by bortezomib/lenalidomide and then with bortezomib/liposomal-doxorubicine/dexamethasone, with partial remission, poor hematological tolerance, and multiple episodes of pneumococcal infection...
2016: Case Reports in Oncological Medicine
https://www.readbyqxmd.com/read/27509033/mobilization-of-autologous-and-allogeneic-peripheral-blood-stem-cells-for-transplantation-in-haematological-malignancies-using-biosimilar-g-csf
#14
M Schmitt, J-M Hoffmann, K Lorenz, A Publicover, A Schmitt, A Nagler
BACKGROUND AND OBJECTIVES: Biosimilars of the granulocyte colony stimulating factor (G-CSF) filgrastim were approved by the European Medicines Agency (EMA) for registered indications of the originator G-CSF, including prevention and treatment of neutropenia, as well as mobilization of peripheral blood stem cells in 2008. Nevertheless, there is still an ongoing debate regarding the quality, efficacy and safety of biosimilar G-CSF. MATERIALS AND METHODS: This article is a meta-analysis of clinical studies on the use of biosimilar G-CSF for mobilization and transplantation of haematopoietic stem cells as available in public databases...
August 2016: Vox Sanguinis
https://www.readbyqxmd.com/read/27447610/immunomodulation-induced-by-stem-cell-mobilization-and-harvesting-in-healthy-donors-increased-systemic-osteopontin-levels-after-treatment-with-granulocyte-colony-stimulating-factor
#15
Guro Kristin Melve, Elisabeth Ersvaer, Çiğdem Akalın Akkök, Aymen Bushra Ahmed, Einar K Kristoffersen, Tor Hervig, Øystein Bruserud
Peripheral blood stem cells from healthy donors mobilized by granulocyte colony-stimulating factor (G-CSF) and harvested by leukapheresis are commonly used for allogeneic stem cell transplantation. The frequency of severe graft versus host disease is similar for patients receiving peripheral blood and bone marrow allografts, even though the blood grafts contain more T cells, indicating mobilization-related immunoregulatory effects. The regulatory phosphoprotein osteopontin was quantified in plasma samples from healthy donors before G-CSF treatment, after four days of treatment immediately before and after leukapheresis, and 18-24 h after apheresis...
2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27427920/ykl-40-in-allogeneic-hematopoietic-cell-transplantation-after-aml-and-myelodysplastic-syndrome
#16
B Kornblit, T Wang, S J Lee, S R Spellman, X Zhu, K Fleischhauer, C Müller, M R Verneris, K Müller, J S Johansen, L Vindelov, P Garred
YKL-40, also called chitinase-3-like-1 protein, is an inflammatory biomarker that has been associated with disease severity in inflammatory and malignant diseases, including AML, multiple myeloma and lymphomas. The objective of the current study was to assess the prognostic value of pretransplant recipient and donor plasma YKL-40 concentrations in patients with AML (n=624) or myelodysplastic syndrome (n=157) treated with allogeneic hematopoietic cell transplantation (HCT). In recipients, the plasma YKL-40 concentrations were increased when the HCT-comorbidity index was ⩾5 (P=0...
July 18, 2016: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/27403738/sequential-ccr5-tropic-hiv-1-reactivation-from-distinct-cellular-reservoirs-following-perturbation-of-elite-control
#17
Sarah A Watters, Petra Mlcochova, Frank Maldarelli, Nilu Goonetilleke, Deenan Pillay, Ravindra K Gupta
BACKGROUND: HIV Elite Controllers may reveal insights into virus persistence given they harbour small reservoir sizes, akin to HIV non-controllers treated early with combination antiretroviral therapy. Both groups of patients represent the most promising candidates for interventions aimed at sustained remission or 'cure'. Analytic treatment interruption (ATI) in the latter group leads to stochastic rebound of virus, though it is unclear whether loss of elite control is also associated with similar rebound characteristics...
2016: PloS One
https://www.readbyqxmd.com/read/27311084/chronic-persistent-parvovirus-b19-bone-marrow-infection-resulting-in-transfusion-dependent-pure-red-cell-aplasia-in-multiple-myeloma-after-allogeneic-haematopoietic-stem-cell-transplantation-and-severe-graft-versus-host-disease
#18
Matthias Karrasch, Volker Schmidt, Andreas Hammer, Andreas Hochhaus, Paul La Rosée, Iver Petersen, Andreas Sauerbrei, Michael Baier, Herbert G Sayer, Beate Hermann
INTRODUCTION: We report a chronic persistent Parvovirus B19 (PVB19) infection despite long-term immunoglobulin substitution intravenous immunoglobulin (IVIG) and tapering of immune-suppressive therapy in a 41-year-old patient after allogeneic haematopoietic stem cell transplantation (alloHSCT) and long-term immune-suppressive therapy due to a steroid-refractory graft versus host disease (GvHD). CLINICAL COURSE: More than 18 month after alloHSCT the patient acquired a de novo transfusion-dependent pure red cell aplasia (PRCA) due to a PVB19 infection...
June 16, 2016: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/27307594/checkpoint-inhibition-of-kir2d-with-the-monoclonal-antibody-iph2101-induces-contraction-and-hyporesponsiveness-of-nk-cells-in-patients-with-myeloma
#19
Mattias Carlsten, Neha Korde, Ritesh Kotecha, Robert Reger, Simona Bor, Dickran Kazandjian, Ola Landgren, Richard W Childs
PURPOSE: Immune checkpoint inhibitors have recently revolutionized cancer immunotherapy. Based on data showing KIR-ligand mismatched NK-cells reduce the risk of leukemia and multiple myeloma (MM) relapse following allogeneic hematopoietic stem cell transplantation, investigators have developed a checkpoint inhibition antibody that blocks KIR on NK-cells. Although in vitro studies suggest the KIR2D-specific antibody IPH2101 induces KIR-ligand mismatched tumor killing by NK-cells, our single-arm phase II clinical trial in patients with smoldering MM was prematurely terminated due to lack of clinical efficacy...
June 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27249701/moving-beyond-autologous-transplantation-in-multiple-myeloma-consolidation-maintenance-allogeneic-transplant-and-immune-therapy
#20
Amrita Krishnan, Ravi Vij, Jesse Keller, Binod Dhakal, Parameswaran Hari
For multiple myeloma, introduction of novel agents as part of the front-line treatment followed by high-dose chemotherapy and autologous hematopoietic stem cell transplantation (ASCT) induces deep responses in a majority of patients with this disease. However, disease relapse is inevitable, and, with each relapse, the remission duration becomes shorter, ultimately leading to a refractory disease. Consolidation and maintenance strategy after ASCT is one route to provide sustained disease control and prevent repeated relapses...
2016: American Society of Clinical Oncology Educational Book
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