Search results for "Melphalan"
showing 10 items of 29 documents
A 13 mer LNA-i-miR-221 Inhibitor Restores Drug Sensitivity in Melphalan-Refractory Multiple Myeloma Cells.
2016
Abstract Purpose: The onset of drug resistance is a major cause of treatment failure in multiple myeloma. Although increasing evidence is defining the role of miRNAs in mediating drug resistance, their potential activity as drug-sensitizing agents has not yet been investigated in multiple myeloma. Experimental Design: Here we studied the potential utility of miR-221/222 inhibition in sensitizing refractory multiple myeloma cells to melphalan. Results: miR-221/222 expression inversely correlated with melphalan sensitivity of multiple myeloma cells. Inhibition of miR-221/222 overcame melphalan resistance and triggered apoptosis of multiple myeloma cells in vitro, in the presence or absence of…
Pembrolizumab as Consolidation Strategy in Patients with Multiple Myeloma: Results of the GEM-Pembresid Clinical Trial
2020
PD1 expression in CD4+ and CD8+ T cells is increased after treatment in multiple myeloma patients with persistent disease. The GEM-Pembresid trial analyzed the efficacy and safety of pembrolizumab as consolidation in patients achieving at least very good partial response but with persistent measurable disease after first- or second-line treatment. Moreover, the characteristics of the immune system were investigated to identify potential biomarkers of response to pembrolizumab. One out of the 17 evaluable patients showed a decrease in the amount of M-protein, although a potential late effect of high-dose melphalan could not be ruled out. Fourteen adverse events were considered related to pem…
CD52‐negative T cells predict acute graft‐versus‐host disease after an alemtuzumab‐based conditioning regimen
2020
Allogeneic haematopoietic stem cell transplantation (HSCT) after a reduced-intensity conditioning (RIC) regimen with fludarabine, melphalan and alemtuzmab is an effective therapy for haematological malignancies. Alemtuzumab, a monoclonal antibody against CD52, a glycosylphosphatidylinositol-anchor-bound surface protein on lymphocytes, depletes T cells to prevent graft-versus-host disease (GVHD). Despite this, acute and chronic GVHD (a/cGVHD) remain life-threatening complications after HSCT. The aim of the present study was to identify parameters to predict GVHD. In 69 patients after HSCT, T-cell subsets were functionally analysed. Reconstitution of CD52neg T cells and CD52neg regulatory T c…
Intravenous injection of bortezomib, melphalan and dexamethasone in refractory and relapsed multiple myeloma
2013
Abstract Background A combination of bortezomib (1.3 mg/m2), melphalan (5 mg/m2), and dexamethasone (40 mg) (BMD), with all three drugs given as a contemporary intravenous administration, was retrospectively evaluated. Patients and methods Fifty previously treated (median 2 previous lines) patients with myeloma (33 relapsed and 17 refractory) were assessed. The first 19 patients were treated with a twice-a-week (days 1, 4, 8, 11, ‘base’ schedule) administration while, in the remaining 31 patients, the three drugs were administered once a week (days 1, 8, 15, 22, ‘weekly’ schedule). Results Side-effects were predictable and manageable, with prominent haematological toxicity, and a better tox…
Nonmyeloablative stem cell transplantation in adults with high-risk ALL may be effective in early but not in advanced disease
2002
The feasibility of nonmyeloablative stem cell transplantation (NST) was evaluated in 22 adults with high-risk ALL. 16/22 patients had advanced disease and 11/22 had Ph+ ALL. Eleven patients received NST as first stem cell transplantation (SCT). Eleven patients had relapses after allogeneic or autologous SCT and underwent a salvage NST. 18/22 patients (82%) engrafted after NST. 13/16 patients (81%) with active disease reached complete remission (CR). 11 of 13 patients developed GVHD. After first NST 10/11 patients (91%) engrafted. Six of seven patients with active disease reached CR. Three of five relapsing patients reached subsequent CR after donor lymphocyte infusions, termination of immun…
Qip-Mass Spectrometry in High Risk Smoldering Multiple Myeloma Patients Included in the GEM-CESAR Trial: Comparison with Conventional and Minimal Res…
2019
Introduction: The GEM-CESAR trial is a potentially curative strategy for high-risk smoldering multiple myeloma (HRsMM) patients in which the primary endpoint is the assessment of bone marrow minimal residual disease negativity by next generation flow (NGF). However, alternative methods of tumor burden evaluation in serum, like Quantitative Immunoprecipitation Mass Spectrometry (QIP-MS), a polyclonal antibody-based technology to identify intact immunoglobulins, have been also evaluated. Patients and Methods: Ninety HRsMM patients included in the GEM-CESAR trial received six 4-weeks cycles of carfilzomib, lenalidomide and dexamethasone followed by high dose melphalan and ASCT and 2 further cy…
Fatal neuroinvasion and SARS-CoV-2 tropism in K18-hACE2 mice is partially independent on hACE2 expression
2022
ABSTRACTAnimal models recapitulating distinctive features of severe COVID-19 are critical to enhance our understanding of SARS-CoV-2 pathogenesis. Transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) under the cytokeratin 18 promoter (K18-hACE2) represent a lethal model of SARS-CoV-2 infection. The precise mechanisms of lethality in this mouse model remain unclear. Here, we evaluated the spatiotemporal dynamics of SARS-CoV-2 infection for up to 14 days post-infection. Despite infection and moderate pneumonia, rapid clinical decline or death of mice was invariably associated with viral neuroinvasion and direct neuronal injury (including brain and spinal neurons). Neuroinv…
Initial chemotherapy with mitoxantrone, chlorambucil, prednisone impairs the collection of stem cells in patients with indolent lymphomas—results of …
2006
Myeloablative radio-chemotherapy with subsequent autologous stem cell transplantation (ASCT) significantly prolongs progression free and probably overall survival in follicular lymphoma (FL) in first remission. The current trial explored prospectively the rate of successful stem cell mobilization in patients with advanced stage FL after initial therapy with either Mitoxantrone, Chlorambucil, Prednisone (MCP) or Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (CHOP) as part of a prospective randomized comparison of both regimens. ASCT patients received Dexa-BEAM (Dexamethasone, BCNU, Melphalan, Etoposide, Cytarabine) for mobilization of stem cells. Stem cells were collected and a mini…
A Time-to-Event Model for Acute Kidney Injury after Reduced-Intensity Conditioning Stem Cell Transplantation Using a Tacrolimus- and Sirolimus-based …
2017
There is a paucity of data evaluating acute kidney injury (AKI) incidence and its relationship with the tacrolimus-sirolimus (Tac-Sir) concentrations in the setting of reduced-intensity conditioning (RIC) after allogeneic stem cell transplantation (allo-HSCT). This multicenter retrospective study evaluated risk factors of AKI defined by 2 classification systems, Kidney Disease Improving Global Outcome (KDIGO) score and "Grade 0-3 staging," in 186 consecutive RIC allo-HSCT recipients with Tac-Sir as graft-versus-host disease prophylaxis. Conditioning regimens consisted of fludarabine and busulfan (n = 53); melphalan (n = 83); or a combination of thiotepa, fludarabine, and busulfan (n = 50). …
Protective effect of O6-methylguanine-DNA methyltransferase (MGMT) on the cytotoxic and recombinogenic activity of different antineoplastic drugs
1996
The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) removes alkyl groups from the O6 position of guanine in DNA and thus may protect cells against genotoxic effects of agents inducing this lesion. To analyze quantitatively the level of protection mediated by MGMT against antineoplastic drugs, we determined the cytotoxic and recombinogenic (sister-chromatid exchange inducing) effects of various chemotherapeutic agents in a pair of isogenic Chinese hamster cell lines deficient and proficient for MGMT, generated upon transfection with human MGMT cDNA. Furthermore, we compared the responses of the human cell lines HeLa MR (MGMT deficient) and HeLa S3 (MGMT proficient) to the va…