Onset Of Myeloma Research Articles

Correlation of C-MYC Protein, MDSC and Th17 Cells with Pathogenesis of Myeloma in Different Clinical Stages

To investigate the correlation of C-MYC protein with MDSC, Th17 cells and the pathogenesis of myeloma in different clinical stages. A total of 65 patients with multiple myeloma treated in our hospital were selected as MM group, and 30 healthy subjects were selected as control group. The positive expression rate of C-MYC protein in bone marrow tissue, and the ratios of peripheral blood MDSC and Th17 cells were compared among the two groups, and the correlation of C-MYC protein, the ratio of MDSC, Th17 cells with onset of myeloma at different clinical stages, the relationship of the expression of C-MYC protein with the ratio of MDSC/Th17 cells and the clinical parameters of MM was analyzed. Also, the diagnostic value of single diagnosis and combined diagnosis was compared. The positive expression rate of C-MYC protein in bone marrow, the ratio of MDSC and Th17 cells in peripheral blood in MM group were significantly higher than those in normal control group(P＜0.05); the positive expression rate of C-MYC protein, MDSC and Th17 cells in patients at ISS stage Ⅰ, Ⅱ and Ⅲ MM showed an increasing trend (r=0.432, r=0.401, r=0.351); the correlation between the ratio of MDSC, Th17 cells and the positive expression rate of C-MYC protein in MM patients was positive (r=0.415, r=0.417); the area under ROC curve (AUC) of combined diagnosis was significantly larger than that of single index diagnosis (C-MYC protein, MDSC cells, Th17 cells)(P＜0.05). There was no correlation between the expression of C-MYC protein, the proportion of MDSC, Th17 cells and sex or age in MM patients (P＞0.05). The positive expression rate of C-MYC protein and the proportion of MDSC and Th17 cells in MM patients significantly increase, which positively correlates with clinical ISS stagin.

Correlation of C-MYC Protein, MDSC and Th17 Cells with Pathogenesis of Myeloma in Different Clinical Stages

To investigate the correlation of C-MYC protein with MDSC, Th17 cells and the pathogenesis of myeloma in different clinical stages. A total of 65 patients with multiple myeloma treated in our hospital were selected as MM group, and 30 healthy subjects were selected as control group. The positive expression rate of C-MYC protein in bone marrow tissue, and the ratios of peripheral blood MDSC and Th17 cells were compared among the two groups, and the correlation of C-MYC protein, the ratio of MDSC, Th17 cells with onset of myeloma at different clinical stages, the relationship of the expression of C-MYC protein with the ratio of MDSC/Th17 cells and the clinical parameters of MM was analyzed. Also, the diagnostic value of single diagnosis and combined diagnosis was compared. The positive expression rate of C-MYC protein in bone marrow, the ratio of MDSC and Th17 cells in peripheral blood in MM group were significantly higher than those in normal control group(P＜0.05); the positive expression rate of C-MYC protein, MDSC and Th17 cells in patients at ISS stage Ⅰ, Ⅱ and Ⅲ MM showed an increasing trend (r=0.432, r=0.401, r=0.351); the correlation between the ratio of MDSC, Th17 cells and the positive expression rate of C-MYC protein in MM patients was positive (r=0.415, r=0.417); the area under ROC curve (AUC) of combined diagnosis was significantly larger than that of single index diagnosis (C-MYC protein, MDSC cells, Th17 cells)(P＜0.05). There was no correlation between the expression of C-MYC protein, the proportion of MDSC, Th17 cells and sex or age in MM patients (P＞0.05). The positive expression rate of C-MYC protein and the proportion of MDSC and Th17 cells in MM patients significantly increase, which positively correlates with clinical ISS stagin.

New Bioaccumulations of Toxins in Resident Coastal Dolphins Signal Dangers of Human Myeloma.

Dolphins and humans are exposed to the same toxins in seafood. Over 2 billion people worldwide rely on seafood as their major source of protein and 60% of people live in coastal areas. Resident coastal dolphins are exposed to marine pollution in the same fashion as humans who frequently consume seafood, thus any indication of disease in dolphins has implications both for humans who eat regularly from the same areas and/or are otherwise exposed to the same toxins.Although ecotoxicologic studies of marine environments are very complex, (Irwin: Aquatic Mammals 31: 195–225, 2005), the bottlenose dolphin is a sentinel species for biomonitoring purposes. Tissue levels of many known carcinogens such as DDT, DDE, dioxins (e.g. PCDDs and 2,3,7,8 TCDD), BaP, PAHs, and more recently PFC and PBDEs (water repellants and fire retardants), reflect bioaccumulation in both dolphins and humans. Target sites where human and dolphin disease have been contrasted and compared are: North America (Alaska; Puget Sound; San Francisco Bay; Gulf Coast and Florida; St. Lawrence Seaway); Japan (Osaka Bay); Sweden; Coastal UK and Hong Kong (Pearl River estuary). For Alaska, Florida, Japan, Sweden and coastal UK, there are highly significant correlations between fish contamination/consumption and excess risk of human myeloma. In Alaska, Inuit men eat contaminated fish, have high organochloride (dioxins) levels in blood and tissues and an increased risk of myeloma. Likewise for Swedish fisherman comparing Baltic (more contamination) versus west coast levels of dioxins and myeloma. In Japan, a case control study provides a highly significant odds ratio of 5.89 for agriculture/fisheries as occupational factors. A separate study gives an annual age adjusted incidence of 7.03/100,000 for the Osaka Bay fishing region. Around Lake Okeechobee Florida an incidence rate of 6.52/100,000 correlates with both contamination and commercial fishing licenses.Although dolphins share most human mammalian genes, including CYP1A and CYP2B, they lack the ability to adequately catabolize type I and II dioxins, which therefore preferentially accumulate. Unfortunately, observed results of these bioaccumulations are suppressed immunity, infections and cancers particularly B-cell lymphomas and “myeloma-like” immunoblastic lymphomas (Bossart: J. Vet Diagn Invest 9: 454–458, 1997). This pattern of diseases in turn corresponds with the local and systemic effects exemplified in Balb/c mice during pristine-induced plasmacytogenesis and in humans exposed to toxins.Newly recognized persistent organic pollutants such as water repellants (PFCs) and flame-retardants (PBDEs) are a particular concern, both because of rapid recent bioaccumulation in dolphins with associated disease manifestations plus the potential for wide global dispersal and diverse routes of human exposure. Numerous consumer goods contain PBDEs, including electronics, carpets, furniture and textiles. Genetic studies help refine probability calculations to assess risk using the union rule for independent events. Studies are now underway to correlate recent bioaccumulations in dolphins and humans, genetic predisposition and myeloma onset. Probability calculations for risk of developing myeloma will support interventions to reduce both contamination of the marine environment and elimination of human toxin exposures.

Plasma Exchange for Acute Renal Failure of Myeloma-Logical, Yet Ineffective: Plasma Exchange When Myeloma Presents as Acute Renal Failure. A Randomized, Controlled Trial. Ann Int Medicine 143: 777-784, 2005.

Plasma Exchange for Acute Renal Failure of Myeloma-Logical, Yet Ineffective: Plasma Exchange When Myeloma Presents as Acute Renal Failure. A Randomized, Controlled Trial. Ann Int Medicine 143: 777-784, 2005.

Autologous stem cell transplantation for multiple myeloma in patients over 70 years: A matched comparison with patients under 65 years

Background: High dose therapy with autologous stem cell rescue has been shown to prolong survival in patients with multiple myeloma in randomized controlled trials. However, most of the prospective studies have included younger patients, usually 65 or less. It is important to have a better understanding of the outcome of transplantation in the older patients given the median age of onset of myeloma of 65 years. We retrospectively reviewed our institutions experience with high dose therapy for patients over 70 years. Methods: We identified 35 patients with multiple myeloma, from the transplant database, who were at or over the age of 70 at the time of their high dose therapy. We matched these patients to 70 patients (two matches for each patient), based on stage at transplant (primary refractory, plateau phase, relapse off therapy, or relapse on therapy), Durie Salmon stage, high or low labeling index, conventional cytogenetics (abnormal vs normal), presence or absence of circulating plasma cells at time of transplant, and whether cyclophosphamide was used as part of mobilization in that order of priority. Results: The median age of the two groups were 55.3 (Range 37.3–64.8) and 71.7 (Range 70–75.8) years at the time of transplant. The median time to transplant from diagnosis was similar (6.4 for the older patients compared to 6.9 months for the other, P = NS). Ten of the 35 older patients received reduced dose melphalan (140 mg/2)) compared to 3 patients in the control group; P Conclusions: High dose therapy and autologous stem cell transplantation is feasible in selected patients with multiple myeloma over 70 years. It is likely that these older patients were selected based on their overall performance status, a factor that is difficult to analyze in this retrospective review. Nearly 70% of the elderly patients received full dose melphalan for conditioning (200 mg/m2). The toxicity of transplant as well as the outcome appears to be very similar to the younger patients. Patients with multiple myeloma should not be excluded from high dose therapy solely on the basis of their chronological age.

Plasma exchange when myeloma presents as acute renal failure: a randomized, controlled trial.

Two small, randomized trials provide conflicting evidence about the benefits of plasma exchange for patients with acute renal failure at the onset of multiple myeloma. To assess the effect of 5 to 7 plasma exchanges on a composite outcome in patients with acute renal failure at the onset of multiple myeloma. Randomized, open, controlled trial, stratified by chemotherapy and dialysis dependence, conducted from 1998 to 2004. Hospital plasma exchange units in 14 Canadian medical centers. 104 patients between 18 and 81 years of age with acute renal failure at the onset of myeloma. Study participants were randomly assigned to conventional therapy plus 5 to 7 plasma exchanges of 50 mL per kg of body weight of 5% human serum albumin for 10 days or conventional therapy alone. Ninety-seven participants completed the 6-month follow-up. The primary outcome was a composite measure of death, dialysis dependence, or glomerular filtration rate less than 0.29 mL x s(-2) x m(-2) (<30 mL/min per 1.73 m2). At enrollment, the plasma exchange and control groups were similar for dialysis dependence, chemotherapy, sex, age, hypercalcemia, serum albumin level, 24-hour urine protein level, serum creatinine level, and Durie-Salmon staging. The primary composite end point occurred in 33 of 57 (57.9%) patients in the plasma exchange group and in 27 of 39 (69.2%) patients in the control group (difference between groups, 11.3% [95% CI, -8.3% to 29.1%]; P = 0.36). One third of patients in each group died. The study was small, used a composite outcome, and did not use renal biopsy as an inclusion criterion. Recruiting physicians were blinded to treatment allocation but not to treatment thereafter. In patients with acute renal failure at the onset of multiple myeloma, there is no conclusive evidence that 5 to 7 plasma exchanges substantially reduce a composite outcome of death, dialysis dependence, or glomerular filtration rate less than 0.29 mL.s(-2).m(-2) (<30 mL/min per 1.73 m2) at 6 months.

Light Chain Nephropathy: Histological and Clinical Aspects in 15 Cases

Fifteen patients aged 31-74 years (five male, ten female) on renal biopsy showed intense linear deposits of light chains along tubular basement membranes (TBM) by immunofluorescence, and/or granular dense deposits on electronmicroscopy. Multiple myeloma was diagnosed in ten patients. The onset of myeloma and nephropathy was simultaneous in six patients; nephropathy preceded or followed the diagnosis of myeloma in three and one patients respectively. The mode of onset of nephropathy was acute or rapidly progressive renal failure in five cases, chronic renal failure in seven, and heavy proteinuria in three. Only two patients had normal renal function at biopsy. Serum monoclonal component was kappa in five patients, IgG kappa in three, IgD kappa in one, IgG lambda in one, IgA lambda in one, absent in three, and not detected in one. On light microscopy eight cases had nodular glomerulosclerosis, three cast nephropathy and 14 TBM thickening. Immunofluorescence for monoclonal light chain(s) was positive in 11 of 13 cases. Electron microscopy showed finely granular deposits in the inner side of glomerular basement membranes (GBM) and the outer side of TBM in 11 of 11 tested cases. The evolution was towards chronic renal failure in 12 patients (six of whom required dialysis), death in two, unknown in one. Four patients died after a period of dialysis, from infections or cardiovascular complications.

Nucleolar size in benign and malignant plasma cell proliferation;.

Nucleolar and nuclear size of bone marrow plasma cells has been studied in 26 cases of myeloma, 19 of benign essential monoclonal gammapathy (BEMG) and 9 without an M-component. Bone marrow smears were Feulgen-stained to visualize nucleoli and nuclei. Nucleolar area, nuclear area and the ratio nucleolar area/nuclear area were calculated. The myeloma group differed from the other two groups in having plasma cells with larger nucleoli, larger nuclei and an increased ratio nucleolar area/nuclear area. No difference was found between the BEMG group and the cases without an M-component. In some cases--in which the absence of osteolytic lesions at X-ray examination, a low plasma cell percentage in bone marrow smears or a low M-component concentration initially made the diagnosis of myeloma uncertain--the observation of enlarged nucleoli could help to establish the diagnosis. Three cases were observed in which the onset of myeloma was preceded by a long period of essentially unchanged M-component concentration. In these cases a sudden increase of M-component concentration was accompanied by an increase of mean nucleolar size of bone marrow plasma cells.