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Autologous bone marrow Th cells can support multiple myeloma cell proliferation in vitro and in xenografted mice.

Multiple myeloma (MM) is a plasma cell malignancy where MM cell growth is supported by the bone marrow (BM) microenvironment with poorly defined cellular and molecular mechanisms. MM cells express CD40, a receptor known to activate autocrine secretion of cytokines and elicit proliferation. Activated T helper (Th) cells express CD40 ligand (CD40L) and BM Th cells are significantly increased in MM patients. We hypothesized that activated BM Th cells could support MM cell growth. We here found that activated autologous BM Th cells supported MM cell growth in a contact- and CD40L-dependent manner …

Autoantibodies against β1-adrenergic receptor: response to induction therapy with bortezomib-containing regimens for multiple myeloma patients.

This study aims to investigate the predictive value of pre-chemotherapy β1R-AABs by evaluating the response of newly diagnosed symptomatic multiple myeloma (MM) patients to their treatment with a bortezomib-containing regimen. Forty-five de novo MM patients and 50 normal controls (NCs) were prospectively enrolled in this study. Serum titers of β1R-AABs were detected by ELISA. These 45 MM patients were divided into two groups (positive and negative groups) according to their β1R-AABs. Follow-up examinations were performed on these patients during chemotherapy induction. The final analysis cover…

Cost-Effectiveness of Novel Agents in Medicare Patients with Multiple Myeloma: Findings from a U.S. Payer's Perspective.

BackgroundSince multiple myeloma (MM) incurs a substantial economic burden in care management, more and more discussion has been generated in recent years about the costs of novel antimyeloma drugs and their associated value. Because of these costs, economic assessment that quantifies value of care over the long-term is essential.ObjectiveTo determine the cost-effectiveness (measured as cost per life-year saved) of front-line novel agent-based therapy use among a cohort of elderly patients with MM in a real-world setting.MethodsWe identified 2,551 elderly patients with advanced MM from 2000 to…

Relapsed Multiple Myeloma Presenting as Intracranial Plasmacytoma and Malignant Pericardial Effusion following Recent Allogeneic Stem Cell Transplantation.

Although rare, both central nervous system and pericardial involvement of myeloma have been well described in the literature. Their simultaneous occurrence in relapsed disease, however, has not been previously reported. This case describes a 54-year-old female who was treated for high-risk multiple myeloma with multiregimen chemotherapy and allogeneic hematopoietic stem cell transplantation. Four months after transplant, she was found to have relapsed disease manifesting as an extraosseous, intracranial plasmacytoma and simultaneous malignant pericardial effusion. Her disease characteristics, …

Concurrent multiple myeloma and mast cell neoplasia in a 13-year-old castrated male Maine Coon cat.

A 13-year-old, castrated male Maine Coon cat was presented to Oklahoma State University Boren Veterinary Medical Teaching Hospital for yearly echocardiographic examination monitoring hypertrophic cardiomyopathy (HCM) diagnosed in 2003. Physical examination revealed a heart murmur and premature beats, likely related to HCM, but was otherwise unremarkable. A biochemistry profile revealed a hyperglobulinemia (6.3 g/dL). Cytologic examination of fine-needle aspirates from liver and spleen revealed increased numbers of plasma cells and mast cells, confirmed with subsequent histologic examination. I

Multiple myeloma presenting with bilateral ankle pain (microangiopathy) and complicated by streptococcal meningitis and Pneumocystis carinii pneumonia.

Multiple myeloma is characterised by the neoplastic proliferation of a single clone of plasma cells producing a monoclonal immunoglobulin. This clone of plasma cells proliferates in the bone marrow, resulting in extensive skeletal destruction with osteolytic lesions, osteopenia and pathological fractures. Additional disease-related complications include hypercalcaemia, renal insufficiency, anaemia and infection. We present the case of a 64-year-old woman presenting with rapid onset, painful distal symmetrical lower limb weakness and an acute kidney injury. Owing to her IgG κ paraprotein (kappa…

Ischemic colitis diagnosed by magnetic resonance imaging during lenalidomide treatment in a patient with relapsed multiple myeloma.

INTRODUCTION: Multiple myeloma is the second most common hematological neoplasm that also affects young patients. The progression-free survival after autologous stem cell transplant has improved with the introduction of several novel agents such as lenalidomide, which may, however, increase the risk of adverse events. METHODS: We describe the case of a 54-year-old woman with relapse of multiple myeloma 3 years after myeloablative allogeneic stem cell transplant who developed abdominal pain and bloody diarrhea following 7 months of lenalidomide therapy. RESULTS: Abdominal plain x-ray and magn…

Lenalidomide and low-dose dexamethasone in Japanese patients with newly diagnosed multiple myeloma: A phase II study.

In the FIRST trial (MM-020), lenalidomide plus low-dose dexamethasone (Rd) reduced the risk of disease progression or death compared with combination melphalan-prednisone-thalidomide. As the FIRST trial did not include any Japanese patients, the efficacy and safety of continuous treatment with Rd was evaluated in 26 Japanese patients with newly diagnosed multiple myeloma (NDMM) in a single-arm, multicenter, open-label phase II trial (MM-025). Patients received lenalidomide on days 1-21 of each 28-day cycle, with a starting dose of 25 mg/day (dose adjusted for renal impairment), and 40 mg/day d…

Managing neutropenia by pegfilgrastim in patients affected by relapsed/refractory multiple myeloma treated with bendamustine-bortezomib-dexamethasone.

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… Multiple myeloma (MM) in advanced phases of disease may be managed by regimens combining agents not frequently employed in early phases of treatment (e.g., anthracyclines, alkylating agents, etc), which have significant myelotoxicity. … Bendamustine-bortezomib-dexamethasone is an active and well-tolerated regimen in patients with relapsed or refractory multiple myeloma. Blood. 2014;123(7):985–991. doi: 10.1182/blood-2013-08-521468. 10. …

Simplified response monitoring criteria for multiple myeloma in patients undergoing therapy with novel agents using computed tomography.

INTRODUCTION: Multiple myeloma is a malignant hematological disorder of the mature B-cell lymphocytes originating in the bone marrow. While therapy monitoring is still mainly based on laboratory biomarkers, the additional use of imaging has been advocated due to inaccuracies of serological biomarkers or in a-secretory myelomas. Non-enhanced CT and MRI have similar sensitivities for lesions in yellow marrow-rich bone marrow cavities with a favourable risk and cost-effectiveness profile of CT. Nevertheless, these methods are still limited by frequently high numbers of medullary lesions and its t…

Multiple Myeloma-Like Spinal MRI Findings in Skeletal Fluorosis: An Unusual Presentation of Fluoride Toxicity in Human.

Endemic fluorosis is a worldwide environmental problem due to excessive fluoride, commonly due to increased drinking water fluoride levels but sometimes due to other sources such as food with high fluoride content. In India, 21 of the 35 states are known to have health problems associated with fluoride toxicity. The present report is a case of a 50-year-old female who was seen with progressive spinal complications and a MRI of the spine suggestive of multiple myeloma. The MRI of the lumbosacral spine showed a diffuse and heterogeneous marrow signal of the lower dorsal and lumbosacral vertebrae…

Patients with multiple myeloma have excellent long-term outcomes after recovery from dialysis-dependent acute kidney injury.

OBJECTIVES: The aim of this study was to report the long-term outcomes in patients with multiple myeloma (MM) who receive dialysis treatment for acute kidney injury (AKI) due to myeloma cast nephropathy and subsequently recover renal function. METHODS: Patients presenting with dialysis-dependent AKI secondary to myeloma cast nephropathy and subsequently recovering independent renal function between January 2005 and December 2012 were included in this study. Both renal and haematological parameters were collected at multiple time points as part of routine clinic practice. Factors associated wi…

Utility of serum free light chain measurements in multiple myeloma patients not achieving complete response to therapy.

Normalization of the serum-free light-chain ratio (FLCr) with the absence of bone marrow monoclonal plasma cells following achievement of a complete response (CR) to therapy denotes a stringent CR in multiple myeloma (MM), and is associated with improved overall survival (OS). However, its value in patients achieving <CR is not clear. We hypothesized that patients achieving a normalization of FLCr with initial therapy of MM will have an improved outcome, even in the absence of a CR. We retrospectively evaluated 449 patients with newly diagnosed MM with measurable disease at baseline, who did n…

Extramedullary relapse of multiple myeloma defined as the highest risk group based on deregulated gene expression data.

BACKGROUND: Multiple myeloma (MM) is characterized by malignant proliferation of plasma cells (PC) which accumulate in the bone marrow (BM). The advent of new drugs has changed the course of the disease from incurable to treatable, but most patients eventually relapse. One group of MM patients (10-15%) is considered high-risk because they relapse within 24 months. Recently, extramedullary relapse of MM (EM) has been observed more frequently. Due to its aggressivity and shorter survival, EM is also considered high-risk. AIMS: The goal of this study was to determine if the so-called high-risk g…

MicroRNA-451 regulates stemness of side population cells via PI3K/Akt/mTOR signaling pathway in multiple myeloma.

OBJECTIVES: To describe the ultrastructure and relationship to nerves of the myofibroblast in the human bladder lamina propria, and discuss its possible role in bladder function, including sensing stretch, as the response of the bladder to stretch has been thoroughly investigated by afferent nerve recordings, but specialized stretch sensing organs have yet to be identified. MATERIALS AND METHODS: Flexible cystoscopic bladder biopsies were obtained from patients with detrusor hyper-reflexia and from controls. Systematic electron micrographs were obtained throughout the lamina propria, and the

Phase 1 study of twice-weekly ixazomib, an oral proteasome inhibitor, in relapsed/refractory multiple myeloma patients.

Ixazomib is the first investigational oral proteasome inhibitor to be studied clinically. In this phase 1 trial, 60 patients with relapsed/refractory multiple myeloma (median of 4 prior lines of therapy; bortezomib, lenalidomide, thalidomide, and carfilzomib/marizomib in 88%, 88%, 62%, and 5%, respectively) received single-agent ixazomib 0.24 to 2.23 mg/m(2) (days 1, 4, 8, 11; 21-day cycles). Two dose-limiting toxicities (grade 3 rash; grade 4 thrombocytopenia) occurred at 2.23 mg/m(2). The maximum tolerated dose was 2.0 mg/m(2), which 40 patients received in 4 expansion cohorts. Patients rece…

Inflammatory markers and development of symptom burden in patients with multiple myeloma during autologous stem cell transplantation.

PURPOSE: Increasing research suggests that inflammation mediates symptom development. In this longitudinal study, we examined inflammatory factors related to the development of high symptom burden during autologous hematopoietic stem cell transplant (AuSCT) for multiple myeloma. EXPERIMENTAL DESIGN: Patients (n = 63) repeatedly reported symptom severity on the MD Anderson Symptom Inventory multiple myeloma module (MDASI-MM) and contributed blood samples periodically for up to 100 days after AuSCT for inflammatory marker assays. The temporal associations between serum inflammatory marker conce…

Activity of 129 single-agent drugs in 228 phase I and II clinical trials in multiple myeloma.

BackgroundMore than 400 preclinical studies report ≥ 1 compound as cytotoxic to multiple myeloma (MM) cells; however, few of these agents became relevant in the clinic. Thus, the utility of such assays in predicting future clinical value is debatable.Patients and methodsWe examined the application of early-phase trial experiences to predict future clinical adoption. We identified 129 drugs explored as single agents in 228 trials involving 7421 patients between 1961 and 2013.ResultsAll drugs in common use in MM (melphalan, dexamethasone, prednisone, cyclophosphamide, bendamustine, thalidomide, …

Immunoglobulin Free Light Chains and GAGs Mediate Multiple Myeloma Extracellular Vesicles Uptake and Secondary NfκB Nuclear Translocation.

Multiple myeloma (MM) is a hematological malignancy caused by a microenviromentally aided persistence of plasma cells in the bone marrow. Monoclonal plasma cells often secrete high amounts of immunoglobulin free light chains (FLCs) that could induce tissue damage. Recently, we showed that FLCs are internalized in endothelial and myocardial cell lines and secreted in extracellular vesicles (EVs). MM serum derived EVs presented phenotypic differences if compared with monoclonal gammopathy of undetermined significance (MGUS) serum derived EVs suggesting their involvement in MM pathogenesis or pro…

Successful Treatment of Gastric Relapse in Multiple Myeloma with Bortezomib after Autologous Hematopoietic Stem Cell Transplantation (autoHSCT).

We report a case of 59-year-old Turkish man with history of mitral valve replacement (MVR) and chronic obstructive pulmonary disease (COPD) who was diagnosed with stage IIIA IgG lambda multiple myeloma (MM) in 1997. He underwent autologous hematopoietic stem cell transplantation after a conditioning regimen with melphalan 200mg per body area (m(2)) in February 2006. On February 2011, he was admitted to the emergency service of university hospital with complaints of hematemesis and melena. Pathological evaluation of gastric biopsy, obtained from a lesion of small gastric curvature, showed the g…