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Paula Cramer, Barbara Eichhorst, Hans Christian Reinhardt, Michael Hallek
Given the current dynamics in the development of novel agents for CLL therapy, the task to find optimal, non-toxic combinations has become the primary goal. This article gives an update of the most interesting novel drugs. The strategy of the German CLL Study Group to use these agents in combinations is described in detail, highlighting the strategy and first results of a recently started series of phase II combination trials, the BXX series using agents such as bendamustine, idelalisib, ibrutinib, obinutuzumab, ofatumumab and venetoclax...
March 2016: Best Practice & Research. Clinical Haematology
H Móciková, J Marková, Ľ Gahérová, Z Král, A Sýkorová, D Belada, V Procházka, L Martinková, T Papajík, T Kozák
High-dose chemotherapy with autologous stem cell transplantation remains the current standard of treatment for young patients with Hodgkin lymphoma in first relapse or in those who are refractory to first-line treatment. The most important prognostic factors in relapses are clinical stage IV, poor performance status, bulky mass, and less than partial remission after salvage chemotherapy. Standard salvage chemotherapy in relapse before autologous transplantation has not been defined; however, DHAP and ICE are most frequently used in this setting...
2016: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
Anat Gafter-Gvili, Ronit Gurion, Pia Raanani, Ofer Shpilberg, Liat Vidal
Data in the literature are lacking regarding the infection-related adverse events of bendamustine-containing regimens. Therefore, we aimed to assess this risk. We conducted a systematic review and meta-analysis of all randomized controlled trials including bendamustine-containing regimens and those administered for any lymphoproliferative disorder or plasma cell dyscrasia compared with any other regimens. A comprehensive search was conducted until December 2015. Two reviewers appraised the quality of trials and extracted data...
October 13, 2016: Hematological Oncology
Masaoki Sasaki, Hiroaki Izumi, Takaaki Yokoyama, Motohiro Kojima, Ako Hosono
Follicular dendritic cell sarcoma (FDCS) is a very rare malignant tumor derived from follicular dendritic cells. Radical resection is the standard therapy for patients with local disease, but an optimal chemotherapy regimen has not been determined for unresectable disease. We report our experience of an FDCS patient with multiorgan involvement. In the present case, disease was only located in the pancreas initially and radical resection was performed. Multiple metastasis developed after the treatment and several factors that indicated a poor prognosis were observed...
October 13, 2016: Hematological Oncology
Seok Jin Kim, Soo-Mee Bang, Yoon Seok Choi, Deog-Yeon Jo, Jin Seok Kim, Hyewon Lee, Hyeon Seok Eom, Dok Hyun Yoon, Cheolwon Suh, Je-Jung Lee, Junshik Hong, Jae Hoon Lee, Youngil Koh, Kihyun Kim, Sung-Soo Yoon, Chang-Ki Min
BACKGROUND: Bendamustine may be a potential treatment option for patients with myeloma, but little is known about the utility of bendamustine as a salvage treatment, especially in Asian patients. METHODS: We performed a multicenter retrospective study of patients with relapsed or refractory myeloma who received bendamustine and prednisone. RESULTS: The records of 65 heavily pre-treated patients, who had undergone bortezomib and lenalidomide treatment (median number of previous treatments: 5), were analyzed...
September 2016: Blood Research
Benjamin Derman, Milli Jain, Elizabeth McAninch, Casey Gashti
A 59-year-old man presented with polyuria and polydipsia immediately following his sixth cycle of rituximab and bendamustine for chronic lymphocytic leukemia. He initially compensated by increasing his oral fluid intake at home, but later developed septic shock and was admitted with orders to be kept nil per os (NPO). This prompted an episode of acute hypernatremia during which he exhibited continued polyuria with inappropriately dilute urine. Desmopressin challenge yielded no response in the urine osmolality, indicating a nephrogenic source of his diabetes insipidus (DI)...
October 10, 2016: Clinical Nephrology
Sara E F Kost, Eric D J Bouchard, Élise LaBossière, Xibiao Ye, Michelle L Queau, William S Liang, Versha Banerji, Spencer B Gibson, Sachin Katyal, James B Johnston
Bendamustine (BEN) has structural similarities to an alkylating agent and a nucleoside analog, and effective against tumor cells that are resistant to standard therapy. In this study we compared the activities of BEN against that of the alkylating agent, chlorambucil (CLB), and the nucleoside analogs, fludarabine (FLU) and deoxyadenosine/pentostatin (dADO/PEN), in primary chronic lymphocytic leukemia (CLL) cells in vitro. Cross-resistance was observed between BEN, CLB and FLU, with previously treated patients or those with a deletion 17p being most resistant...
September 20, 2016: Leukemia Research
Kazuyo Nagashima, Hiroaki Tanaka, Yurie Nagai, Yasumasa Sugita
During treatment for malignant lymphoma, cytopenia can develop for several reasons. In the treatment of cytopenia, various possibilities should be considered because inadequate treatment causes exacerbation of cytopenia and can lead to fatal conditions, such as infection and bleeding. Herein, we describe immune pancytopenia 3 months after the last exposure to chemotherapy in a patient with diffuse large B-cell lymphoma (DLBCL). She suffered from severe pancytopenia after two courses of rituximab and bendamustine therapy for a second relapse of DLBCL...
September 20, 2016: BMJ Case Reports
Dena R Howard, Talha Munir, Anna Hockaday, Andy C Rawstron, Laura Collett, Jamie B Oughton, David Allsup, Adrian Bloor, David Phillips, Peter Hillmen
BACKGROUND: Chronic lymphocytic leukaemia (CLL) is the most common adult leukaemia. Combination immunochemotherapy such as fludarabine, cyclophosphamide and rituximab is the standard first line therapy in fit patients, but there is limited evidence regarding the optimal treatment of patients after relapse. Ofatumumab as monotherapy has been proven to be effective in the treatment of relapsed, refractory CLL, and as it is not myelotoxic, it is an ideal drug to combine with chemotherapy...
2016: Trials
Wataru Munakata, Kensei Tobinai
Non-Hodgkin lymphoma (NHL) is a heterogeneous group of lymphoid malignancies. The treatment strategy for patients with NHL had remained unchanged until the advent of the era of molecular targeting agents. Although rituximab-containing chemotherapy has improved the response rates and survival of patients with B-cell NHL (B-NHL), several subtypes of B-NHL, especially indolent B-NHL and mantle cell lymphoma (MCL), remain incurable. Therefore, novel treatment modalities for B-NHL, especially for indolent B-NHL and MCL, are needed...
November 2016: Expert Opinion on Drug Discovery
I F Khouri, D Sui, E J Jabbour, B I Samuels, F Turturro, G Alatrash, P Anderlini, S Ahmed, B Oran, S O Ciurea, D Marin, A Olson, K K Patel, U R Popat, C Ledesma, T M Kadia, A Ferrajoli, J A Burger, J L Jorgensen, L J Medeiros, R L Bassett, A M Gulbis
Bendamustine has shown a favorable safety profile when included in chemotherapy regimens for several types of lymphoma, including CLL. This study investigated the long-term effect of adding bendamustine to a conditioning regimen on survival, rate of engraftment, immune recovery and GvHD after allogeneic stem cell transplantation (alloSCT) in CLL patients. These outcomes were compared with the fludarabine, cyclophosphamide and rituximab (FCR) conditioning regimen. We reviewed the data for 89 CLL patients treated on three trials at our institution...
September 5, 2016: Bone Marrow Transplantation
Yoshiki Hiraki, Akira Kawano, Hirohisa Shigematsu, Koichiro Miki, Hideyuki Nomura, Shinji Shimoda
A 63-year-old female and a 63-year-old male with resolved HBV infection suffered a relapse of malignant lymphoma. After bendamustine hydrochloride monotherapy, HBV reactivation occurred. Entecavir treatment was commenced immediately, with tests for HBV DNA negative without development of hepatitis. Regular monitoring of HBV DNA based on the guidelines from the Japan Society of Hepatology was useful.
September 2016: Nihon Shokakibyo Gakkai Zasshi, the Japanese Journal of Gastro-enterology
Gabor Kovacs, Sandra Robrecht, Anna Maria Fink, Jasmin Bahlo, Paula Cramer, Julia von Tresckow, Christian Maurer, Petra Langerbeins, Günter Fingerle-Rowson, Matthias Ritgen, Michael Kneba, Hartmut Döhner, Stephan Stilgenbauer, Wolfram Klapper, Clemens-Martin Wendtner, Kirsten Fischer, Michael Hallek, Barbara Eichhorst, Sebastian Böttcher
PURPOSE: To determine the value of minimal residual disease (MRD) assessments, together with the evaluation of clinical response in chronic lymphocytic leukemia according to the 2008 International Workshop on Chronic Lymphocytic Leukemia criteria. PATIENTS AND METHODS: Progression-free survival (PFS) and overall survival of 554 patients from two randomized trials of the German CLL Study Group (CLL8: fludarabine and cyclophosphamide [FC] v FC plus rituximab; CLL10: FC plus rituximab v bendamustine plus rituximab) were analyzed according to MRD assessed in peripheral blood at a threshold of 10(-4) and clinical response...
August 29, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Nicolas Städler, Aijing Shang, Francesc Bosch, Andrew Briggs, Valentin Goede, Aurelien Berthier, Corinne Renaudin, Veronique Leblond
INTRODUCTION: Rituximab plus fludarabine and cyclophosphamide (RFC) is the standard of care for fit patients with untreated chronic lymphocytic leukemia (CLL); however, its use is limited in 'unfit' (co-morbid and/or full-dose F-ineligible) patients due to its toxicity profile. We conducted a systematic review and Bayesian network meta-analysis (NMA) to determine the relative efficacy of commercially available interventions for the first-line treatment of unfit CLL patients. METHODS: For inclusion in the NMA, studies had to be linked via common treatment comparators, report progression-free survival (PFS), and/or overall survival (OS), and meet at least one of the five inclusion criteria: median cumulative illness score >6, median creatinine clearance ≤70 mL/min, existing co-morbidities, median age ≥70 years, and no full-dose F in the comparator arm...
October 2016: Advances in Therapy
Iliyas Khan, Avinash Gothwal, Ashok Kumar Sharma, Arem Qayum, Shashank K Singh, Umesh Gupta
Bendamustine is a drug of choice for the treatment of several cancers including non- Hodgkin lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL). The unstable nature of the drug, however, offers a major obstacle in its effective formulation development. The present study was aimed to achieve improved stability and efficacy of bendamustine via co-polymeric PEG-PLGA nanoparticulate approach. PEG-PLGA co-polymeric conjugate was synthesized and characterized by FT-IR and (1)H NMR spectroscopy. Bendamustine loaded nanoparticles (PLGA and PEG-PLGA) were prepared, optimized and characterized for size, zeta and electron microscopy (SEM and TEM)...
November 2016: International Journal of Biological Macromolecules
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
Le Lu, Keiko Yoshimoto, Atsuho Morita, Hideto Kameda, Tsutomu Takeuchi
We investigated the effects of bendamustine on B cell functions and explored potential clinical applications of the drugs to autoimmune diseases. Proliferation of Ramos cells, a human B cell line, was significantly inhibited by 25-100μM of bendamustine in a dose-dependent manner. Concordantly, IgM secretion from Ramos cells was significantly inhibited at these concentrations by up to 70%. Interestingly, however, the production and secretion of interleukin-10 (IL-10) were dramatically (at least >10-fold) increased by bendamustine at growth inhibitory concentrations...
October 2016: International Immunopharmacology
Xiaojun Liu, Yingjun Jiang, Billie Nowak, Sarah Hargis, William Plunkett
CNDAC (2'-C-cyano-2'-deoxy-1-β-d-arabino-pentofuranosyl-cytosine, DFP10917) and its orally bioavailable prodrug, sapacitabine, are undergoing clinical trials for hematologic malignancies and solid tumors. The unique action mechanism of inducing DNA strand breaks distinguishes CNDAC from other deoxycytidine analogs. To optimize the clinical potentials of CNDAC, we explored multiple strategies combining CNDAC with chemotherapeutic agents targeting distinct DNA damage repair pathways that are currently in clinical use...
October 2016: Molecular Cancer Therapeutics
Adam J Olszewski, Steven P Treon, Jorge J Castillo
INTRODUCTION: Waldenström macroglobulinemia/lymphoplasmacytic lymphoma (WM) is a rare lymphoma affecting older patients. Its management largely relies on small phase II trials and it is unclear how their results translate into clinical practice in the community. METHOD: We evaluated changes in the presentation, management, and survival among 2,666 Medicare beneficiaries diagnosed with WM between 1994 and 2011, using Medicare claims linked to Surveillance, Epidemiology and End Results data...
July 29, 2016: Oncologist
Dominick Lamonica, Daniel A Graf, Mihaela C Munteanu, Myron S Czuczman
: In a single-arm, phase 2 clinical trial, bendamustine-rituximab (BR) demonstrated an overall response rate (ORR) of 82% among 45 patients with relapsed/refractory mantle cell lymphoma (MCL), with manageable tolerability. A prespecified (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) analysis was conducted to assess the predictive value of the metabolic response to BR compared with the response by International Working Group (IWG) criteria. METHODS: Adult patients with relapsed/refractory MCL underwent FDG-PET at screening and following 6 cycles of BR therapy...
July 28, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
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