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Allogeneic transplant in myeloma

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
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
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
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
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
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
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
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
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
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
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
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
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)
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
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
Annalisa Paviglianiti, Erick Xavier, Annalisa Ruggeri, Patrice Ceballos, Eric Deconinck, Jan J Cornelissen, Stephanie Nguyen-Quoc, Natacha Maillard, Guillermo Sanz, Pierre-Simon Rohrlich, Laurent Garderet, Fernanda Volt, Vanderson Rocha, Nicolaus Kroeger, Eliane Gluckman, Nathalie Fegueux, Mohamad Mohty
Although allogeneic stem cell transplantation is not a standard therapy for multiple myeloma, some patients can benefit from this intense therapy. There are few reports on outcomes after umbilical cord blood transplantation in multiple myeloma, and investigation of this procedure is warranted. We retrospectively analyzed 95 patients, 85 with multiple myeloma and 10 with plasma cell leukemia, receiving single or double umbilical cord blood transplantation from 2001 to 2013. Median follow up was 41 months. The majority of patients received a reduced intensity conditioning...
September 2016: Haematologica
Cristina Salvatierra Pérez, Sebastián Valverde Martínez, Óscar Heredero Zorzo, Alejandro Martín Parada
OBJECTIVE: We report two cases of patients with a previous diagnosis of hematologic tumor who present with testicular recurrence, and we carry out a review of the literature regarding the infrequency of this pathology. METHODS: We present a retrospective review of the medical records of two patients diagnosed with hematologic malignancies (acute myelogenous leukemia and multiple myeloma) with occurrence of relapse in the testicle. We reviewed the management and outcome after treatment with bilateral orchiectomy...
May 2016: Archivos Españoles de Urología
Binod Dhakal, Anita D'Souza, Michael Martens, Jonathan Kapke, Alexandra M Harrington, Marcelo Pasquini, Wael Saber, William R Drobyski, Mei Jie Zhang, Mehdi Hamadani, Parameswaran N Hari
BACKGROUND: Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative option for multiple myeloma (MM). We analyzed our experience of allo-HCT in MM and examined outcomes in 77 consecutive patients with MM receiving allo-HCT from matched sibling (n = 69) or unrelated donors (n = 8). The primary objectives were to assess overall survival (OS), progression-free survival (PFS), and non-relapse mortality in these patients. PATIENTS AND METHODS: Sixty-six patients received non-myeloablative/reduced-intensity conditioning regimens, while 11 received myeloablative regimens...
July 2016: Clinical Lymphoma, Myeloma & Leukemia
M Sobh, M Michallet, G Gahrton, S Iacobelli, A van Biezen, S Schönland, E Petersen, N Schaap, F Bonifazi, L Volin, E Meijer, D Niederwieser, J El-Cheikh, R Tabrizi, N Fegeux, J Finke, D Bunjes, J Cornelissen, H Einsele, B Bruno, M Potter, R Fanin, M Mohty, L Garderet, N Kröger
We describe the use and outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for multiple myeloma (MM) in Europe between January 1990 and December 2012. We identified 7333 patients, median age at allo-HSCT was 51 years (range: 18-78), of whom 4539 (62%) were males. We distinguished three groups: (1) allo-HSCT upfront (n=1924), (2) tandem auto-allo-HSCT (n=2004) and (3) allo-HSCT as a second line treatment and beyond (n=3405). Overall, there is a steady increase in numbers of allo-HSCT over the years...
May 20, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Céline Gregoire, Julien Guiot, Gaëlle Vertenoeil, Évelyne Willems, Kaoutar Hafraoui, Jean-Louis Corhay, Renaud Louis, Yves Beguin
OBJECTIVE AND IMPORTANCE: Yellow nail syndrome (YNS) is a rare disorder of unknown aetiology characterized by the triad of yellow nails, lymphoedema and respiratory manifestations. About 200 cases have been reported, but a lot of patients probably elude proper diagnosis because of both variability of symptoms and ignorance of this syndrome by many physicians. The pathogenesis remains unclear, and could involve functional lymphatic abnormalities, microvasculopathy or lymphocyte deficiency, but none of these hypotheses seems fully satisfactory...
February 6, 2016: Acta Clinica Belgica
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