Prognostic factors of multiple myeloma

Multiple myeloma is a heterogeneous disease with survival ranging from a few months to many years. Several clinical parameters (S beta 2-M) are a direct expression of the tumor burden and have been shown by univariate analysis to be related to patient survival. Durie and Salmon developed a myeloma staging system that analyzed the presenting clinical features, response to treatment and survival duration. But this classification is not related to the intrinsic malignancy (labeling index). Many new parameters (genetic alterations, plasma cell evaluation; serum marqueurs, immune dysregulation) related to patient response to chemotherapy and survival duration have been identified. However, they have not yet been included in standard staging and compared with the recognized prognostic parameters in multivariate analysis. There is a need to create a new international myeloma staging system based on biological features of the disease.     

The prognostic value of soluble interleukin-6 receptor in patients with multiple myeloma

BACKGROUND: The effect of interleukin-6 (IL-6), the major growth factor for myeloma cells, may be enhanced by soluble IL-6 receptor (sIL-6R). Therefore, the current study investigated the clinical significance of serum sIL-6R in patients with multiple myeloma (MM). METHODS: Serum levels of sIL-6R were determined by enzyme-linked immunoassay in 55 normal controls, 81 individuals with monoclonal gammopathy of undetermined significance (MGUS), and 164 patients with MM in various phases of the disease. RESULTS: sIL-6R concentrations were higher in MM patients (162.0 +/- 134.6 ng/mL) than in individuals with MGUS (58.9 +/- 36.7 ng/mL) or in controls (45.6 +/- 22.3 ng/mL) (P = 0.0000). sIL-6R was not found to have a significant linear correlation with any other parameter, including IL-6, beta2-microglobulin (beta2-m), and neopterin, either in newly diagnosed cases or during the course of the disease. In addition, there were no statistically significant differences in sIL-6R concentrations between the clinical stages at the time of diagnosis. In univariate logistic regression analysis sIL-6R was a significant but weak prognostic indicator (P = 0.000000). Kaplan-Meier analysis showed that elevated levels of sIL-6R were associated with shorter survival (P = 0.00282). Patients also were stratified according to their serum beta2-m and sIL-6R levels. Patients with low levels of both parameters had a clear survival benefit over the other groups (P = 0.000000). CONCLUSIONS: The correlation between sIL-6R levels and survival is significant but weak, making it unlikely to be of much value in predicting the outcome of patients with MM alone. The results of the current study support the role of sIL-6R levels in improving the prognostic value of beta2-m and in discriminating patients with MM from individuals with MGUS.     

Kappa and lambda light chain proteins--clinical and prognostic significance in patients with multiple myeloma

In 76 patients with multiple myeloma an independent or combined light chain production at a ratio of kappa (kappa) to lambda (lambda) chains of 43:33 was proved. Two groups of patients were formed depending on the type of the light chain production. They were compared by a number of biological, clinical and biochemical parameters, which demonstrate the frequency and pathogenetic participation of the two light chains in the main syndromes of the disease. The therapeutic response and prognostic value were also estimated. Bence Jones (lambda) chains prevail in men, in the III clinical stage of the disease, in patients with tubular proteinuria and in syndromes indicating an advanced stage of evolution of the main process, in non-reversible azotaemia, hypercalcaemia and hypoalbuminemia. The survival rate in thus group of patients is an average of 7 months shorter in comparison with the BJ (kappa) group (the difference is non-significant). The median survival of patients with BJ (kappa) is 30 months and 21 months for BJ (lambda).     

Leptospirosis: prognostic factors associated with mortality

To determine the prognostic factors for leptospirosis, we conducted a retrospective study of data collected in the emergency department of our hospital between 1989 and 1993. Sixty-eight patients, for whom the diagnosis of leptospirosis was based on pertinent clinical and epidemiological data and positive serology, were included in this study. Fifty-six patients (82%) were discharged from the hospital, and 12 (18%) died. Multivariate logistic regression demonstrated that five factors were independently associated with mortality: dyspnea (odds ratio [OR], 11.7; 95% confidence interval [CI], 2.8-48.5; P < .05), oliguria (OR, 9; CI, 2.1-37.9; P < .05); white blood cell count, >12,900/mm3 (OR, 2.5; CI, 1.8-3.5; P < or = .01), repolarization abnormalities on electrocardiograms (OR, 5.9; CI, 1.4-24.8; P < or = .01), and alveolar infiltrates on chest radiographs (OR, 7.3; CI, 1.7-31.7; P < or = .01). Identification of these factors on admission might provide useful selection criteria for patients who need early transfer to the intensive care unit.     

Nitrosoureas in multiple myeloma

A number of cooperative-group and single-institution studies have shown that BCNU used in combination with prednisone alone or with melphalan,cyclophosphamide, and prednisone is useful for remission induction in patients with previously untreated multiple myeloma. In this setting, results with BCNU (and probably CCNU) are as good as (but not superior to)the results obtained to the frequency of remission induction, duration of remission, and survival. BCNU plus prednisone also appears to be equal to melphalan plus prednisone for remission-maintenance therapy, although it is still unclear whether maintenance therapy is superior to discontinuation of therapy during remission. At the present time, the major use of the nitrosoureas in multiple myeloma appears to be for patients who enter remission with conventional alkylating-agent therapy and later relapse. BCNU and CCNU are occasionally effective when used as single agents or in combination with other alkylating agents for relapsing patients. Results of a pilot study at the University of Arizona with low doses of BCNU and adriamycin for patients relapsing on alkylating-agent therapy have been encouraging, with a 54% (seven of 13 patients) incidence of CRs and PRs. The use of this combination in conjunction with vincristine and prednisone for relapsing patients is under investigation by the Southwest Oncology Group.     

Primary hyperparathyroidism associated with multiple myeloma

A 73-year-old woman was diagnosed as primary hyperparathyroidism. Hypercalcemia recurred after parathyroidectomy, though serum calcium concentration temporarily resumed to normal. Hypercalcemia was eventually shown to be due to multiple myeloma. In spite of the frequent association of hypercalcemia with malignant disease and the relative frequency of primary hyperparathyroidism as a cause of hypercalcemia, primary hyperparathyroidism accompanied by multiple myeloma has been considered in only a limited number of reports. Here, the cases in the literature are reviewed and discussed.     

Serum enzymes in heat stroke: prognostic implication

We measured serum creatine kinase (CK), lactate dehydrogenase (LD), aspartate aminotransferase (AST), and serum alanine aminotransferase (ALT) in 26 heat stroke (HS) victims and 10 control (non-heat-exhausted) subjects during annual Hajj in Makkah, Saudi Arabia. On admission to the HS treatment unit, serum CK, AST, ALT, and LD were higher in HS victims than controls (P < 0.05), and at 6, 12, and 24 h were higher than baseline concentration. The patient group was divided into three groups, (a) those who had a quick recovery, (b) those who were critically ill until the end of the Hajj period (7 days), and (c) those who died. Serum enzymes at the time of admission were significantly higher (P < 0.05) in the nonsurviving group (n = 6) and the severely ill (n = 9) than in those who had a quick recovery (n = 11). ROC curves were plotted for each enzyme. The most useful indicator was LD, as it could distinguish significantly between the groups who died and those who had a quick recovery (area under the curve = 0.991 +/- 0.0286). It was followed by CK and AST as useful prognostic factors. When compared with ROC curves for body temperature, anion gap, and serum potassium, the enzyme results were superior prognostic indicators.     

Immunochemical studies in multiple myeloma

Many hospitals are converting to electronic records and allied health professionals are required to modify their traditional documentation practices to accommodate this new technology. This paper discusses a study conducted to determine the computer anxiety and attitudes of physical, occupational, and speech therapists in a large urban teaching hospital before and after the implementation of a computerized documentation system. Fifty-three therapists surveyed with a preinstallation questionnaire reported mild computer anxiety and generally good attitudes about the planned computer system. A greater amount of previous computer use and better self-related computer skills were consistent with less computer anxiety. Seven of the original sample became the first to use the computer system. After their six month trial period, surveys revealed a reduction in computer anxieties. Manual time logs completed before and after the system implementation revealed a significant decrease in total documentation time when using computers.     

Glomerular lesions in multiple myeloma

An autopsy case of multiple myeloma (IgG, lambda type), clinically characterized by decreased glomerular filtration rate, is reported with particular emphasis on changes in the glomeruli of kidneys. Histologically, the glomeruli revealed slight increase in mesangial matrix and focal thickening of tuft capillary wall. Electron-microscopically, deposits were observed in a subendothelial location in the glomerular capillary walls, and inclusions were noted in the cytoplasm of the visceral epithelial cells. Histoimmunofluorescent study of the kidney demonstrated intense focal and slight diffuse positivity against labelled antisera of anti-IgG and anti-lambda type of light chain on the capillary wall of the glomerular tufts. Other immunoglobulins were not demonstrable in capillary walls. These findings represent the intraglomerular deposition of paraprotein of multiple myeloma without amyloidosis.     

Hyperammonemic encephalopathy in multiple myeloma

We report two cases of hyperammonemic encephalopathy in patients with multiple myeloma. This rare complication, whose pathophysiology remains unknown, is associated with disease progression and so with a very bad prognosis. We believe that this complication should be included in the differential diagnosis of encephalopathy occurring in multiple myeloma.     

Immunoregulatory mechanisms in multiple myeloma

This review presents current experimental data regarding immunologic changes associated with multiple myeloma (Table 1). It is becoming increasingly clear that some of the immunologic changes are host responses to the malignant plasma cell clone and monoclonal immunoglobulin. In the last 2 to 3 years an anti-idiotypic response has been clearly documented, and cells expressing CD16 and soluble CD16 have been identified as modulators of myeloma cell growth and differentiation. Abnormalities in B- and T-cell differentiation have been observed, most consistently the deficiency of T4 helper cells. Differences in the immunologic changes point to the provocative hypothesis that, in MGUS and the initial stages of myeloma, immunologic responses play an important role in controlling proliferation of the malignant clone, and at some point the system is overwhelmed or fails, leading to an overt or more aggressive disease. The quest is to understand the genesis of the autoregulatory circuits operative in myeloma. Novel strategies for immunotherapy in management of myeloma will arise through improved understanding of host immune response and its cause-and-effect relationship with myeloma cell growth.     

Magnetic resonance imaging patterns in patients with multiple myeloma

Genetic sensitivity to 6-n-propylthiouracil (PROP) has been reported to predict hedonic response to sweet taste in both women and men. This study was based on a sample of 159 women of different ethnic backgrounds, mean age 27.0 years, and mean body mass index (BMI) 23.2. The women were classified as nontasters (n = 43), regular tasters (n = 70), or supertasters (n = 46) of PROP on the basis of their PROP detection thresholds and the scaling of 5 suprathreshold solutions of PROP and NaCl. Nontasters had thresholds > 1.8 x 10(-4) mol/L PROP and PROP/NaCl ratios < 1.60. Supertasters had thresholds < 3.2 x 10(-5) mol/L PROP and PROP/NaCl ratios > 1.60. Genetic sensitivity to PROP failed to predict sweetness intensity ratings or hedonic response profiles for sucrose solutions. Separating subjects into sucrose "likers" and "dislikers" failed to reveal any significant links to PROP nontaster, taster, or supertaster status in this all-female sample.