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S Vincent Rajkumar

Publications and source records attributed to S Vincent Rajkumar.

At least 55 records · Page 3Linked to original sources
PubMed2005

Monoclonal gammopathies of undetermined significance.

The monoclonal gammopathies include multiple myeloma (MM), monoclonal gammopathy of undetermined significance (MGUS), primary systemic amyloidosis (AL), and Waldenström's macroglobulinemia (WM). At Mayo Clinic, almost 60% of patients with a monoclonal gammopathy have MGUS. MGUS is characterized by the presence of a serum monoclonal protein value <3 g/dL, fewer than 10% plasma cells in the bone marrow, no or a small amount of monoclonal protein in the urine, and absence of lytic bone lesions, anemia, hypercalcemia, or renal insufficiency related to the plasma-cell proliferative process. During long-term follow-up of 241 patients with MGUS seen at Mayo Clinic from 1956 to 1970, MM, WM, AL, or a related disorder developed in 64. To confirm the findings, we conducted a population-based study on MGUS in the 11 counties of southeastern Minnesota from 1960 to 1994. The risk of progression to a malignant plasma-cell disorder was 1% per year.

Cell Transformation, Neoplastic↗
PubMed2005

MGUS and smoldering multiple myeloma: update on pathogenesis, natural history, and management.

Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) are asymptomatic, pre-malignant disorders characterized by monoclonal plasma cell proliferation in the bone marrow and absence of end-organ damage. Recent advances in the pathogenesis, natural history, and prognosis of MGUS and SMM are reviewed. A new risk stratification system to determine the prognosis of MGUS using the size and type of M protein, and the serum free light chain assay is discussed.

Chromosomes, Human, Pair 14↗
PubMed2005

Thalidomide and dexamethasone: therapy for multiple myeloma.

Multiple myeloma is a plasma cell malignancy that remains incurable with current treatment approaches including high-dose therapy and autologous stem cell transplantation. Thalidomide represents a major advance in the treatment of this disorder, having demonstrated significant activity in all phases of the disease. Thalidomide exerts its antimyeloma effect through multiple mechanisms including antiangiogenesis, immunomodulation and induction of apoptosis in tumor cells, as well as its effect on the tumor microenvironment. Corticosteroids have formed the mainstay of myeloma therapy for decades along with the alkylating agents and have demonstrated synergy when used in combination with thalidomide. The combination of thalidomide and dexamethasone has demonstrated remarkable activity in the treatment of both newly diagnosed as well as relapsed myeloma, and has become an important addition to the armamentarium of myeloma therapies. Overall responses of approximately 70% have been seen with this combination in patients with newly diagnosed myeloma. The combination is associated with an increased risk of deep vein thrombosis necessitating routine prophylactic anticoagulation. Other drugs have been added to this combination that also result in improved response rates. Currently, this combination is used in newly diagnosed patients as an induction therapy prior to stem cell transplant, for those who fail to achieve adequate response to dexamethasone alone or in whom a relatively rapid response is desired based on clinical presentation. Thalidomide analogs with a better safety profile are currently undergoing evaluation in the clinic.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Prognostic factors and predictors of outcome of immunoglobulin M monoclonal gammopathy of undetermined significance.

Monoclonal gammopathy of undetermined significance (MGUS) of the immunoglobulin M (IgM) class was diagnosed at our institution in 213 patients who resided in the 11 counties of southeastern Minnesota from 1960 to 1994. The median age at diagnosis was 74 years and the median concentration of serum M-protein was 1.2 g/dL. The 213 patients were monitored for 1567 person-years (median, 6.3 years), during which 71% died. During follow-up, non-Hodgkin's lymphoma (n = 17), Waldenstrom's macroglobulinemia (n = 6), primary amyloidosis (n = 3), and chronic lymphocytic leukemia (n = 3) developed in 29 patients (14%). The number of patients with progression to lymphoid neoplasms was 15.9 times that expected in the general population. The cumulative probabilities of progression to one of these disorders were 10% at 5 years, 18% at 10 years, and 24% at 15 years. The overall average risks for progression were approximately 1.5% per year. Rates of death resulting from other diseases (cardiovascular, cerebrovascular, etc.) were 31% at 5 years, 52% at 10 years, and 65% at 15 years. Multivariate analysis revealed that only the concentration of serum M-protein at diagnosis and the serum albumin value were independent predictors of progression. It was concluded that the patients with IgM MGUS should be followed indefinitely.

Adult↗
PubMed2005

Monoclonal gammopathy of undetermined significance.

Monoclonal gammopathy of undetermined significance (MGUS) is characterized by the presence of a monoclonal protein (M-protein) without evidence of multiple myeloma (MM), Waldenstrom's macroglobulinemia (WM), amyloidosis (AL), or a related plasma cell proliferative disorder. Agarose gel electrophoresis followed by immunofixation is recommended for recognition of an M-protein. Monoclonal gammopathy of undetermined significance is found in approximately 3% of persons > 70 years of age and in about 1% of those > 50 years old. In a series of 1384 patients from Southeastern Minnesota in whom MGUS was diagnosed at Mayo Clinic from 1960 through 1994, the risk of progression was 1% per year. This risk of progression continued even after > or = 25 years of a stable M-protein. The risk for developing MM, WM, or AL was increased 25-fold, 46-fold, and 8.4-fold, respectively. The concentration of the serum M-protein, abnormal serum free light-chain ratio, and the presence an immunoglobulin (Ig)M or an IgA M-protein were risk factors for progression. The presence of a urine M-protein or the reduction of > or = 1 uninvolved immunoglobulins was not a risk factor for disease progression. Patients must be monitored for progressive disease throughout their lives. Variants of MGUS consist of IgM MGUS, biclonal gammopathies, triclonal gammopathies, idiopathic Bence Jones (light-chain) proteinuria, and IgD MGUS. Monoclonal gammopathy of undetermined significance may be associated with many disorders, including lymphoproliferative diseases, leukemia, von Willebrand's disease, connective tissue diseases, and neurologic disorders. Epidemiologic and statistical methods must be used to evaluate these associations.

Aged↗
PubMed2005

Multiple myeloma: diagnosis and treatment.

Major advances have occurred in our understanding of the biology of multiple myeloma (MM) and in its treatment in the past decade. New diagnostic criteria have been developed, and an international Staging System has replaced the Durle-Salmon Staging System. It is now possible to classify MM as standard risk or high risk on the basis of specific Independent prognostic factors. The role of single and double autologous stem cell transplantation has been clarified by randomized trials. Most importantly, thalidomide, bortezomib, and lenalidomide have emerged as new active agents and are being incorporated rapidly into the treatment of both newly diagnosed and relapsed MM. The current approach to the diagnosis, prognosis, and management of MM is reviewed.

Algorithms↗
PubMed2005

Novel approaches to the management of myeloma.

Standard therapy for multiple myeloma, which accounts for 10% of all hematologic malignancies, has been autologous stem cell transplantation (ASCT), alkylator-based chemotherapy, and corticosteroids. Several advances have been made in the treatment of multiple myeloma over the past decade, especially the arrival of new, active agents such as thalidomide (Thalomid), bortezomib (Velcade), and lenalidomide (Revlimid). These have shown significant clinical activity as single agents. Trials are ongoing to incorporate these new agents into the various stages of treatment and to combine them with other effective treatment modalities, including ASCT.

Angiogenesis Inhibitors↗
PubMed2005

Combination therapy with thalidomide and dexamethasone in patients with newly diagnosed multiple myeloma not undergoing upfront autologous stem cell transplantation: a phase II trial.

BACKGROUND AND OBJECTIVES: Thalidomide plus dexamethasone (Thal/Dex) has emerged as an effective alternative to vincristine, doxorubicin and dexamethasone as a pre-transplant induction therapy for newly diagnosed multiple myeloma. However, many patients treated initially with Thal/Dex do not proceed to autologous stem cell transplantation (ASCT) and the time to progression and other outcome measures with Thal/Dex as primary therapy for multiple myeloma are not known. We present the first data on the outcome of patients with newly diagnosed multiple myeloma treated with Thal/Dex who did not undergo upfront ASCT. DESIGN AND METHODS: We identified 21 patients with newly diagnosed multiple myeloma treated with Thal/Dex on a phase II clinical trial who did not undergo ASCT due to age, comorbidity or the patient's refusal. Patients received thalidomide at a dose of 200 mg/day orally and dexamethasone 40 mg daily on days 1-4, 9-12, 17-20 (odd months) and days 1-4 (even months). Cycles were repeated every 28 days. RESULTS: The median age was 66 years (range 36-78). The median duration of follow-up was 21 months (range 1-52). One (5%) patient achieved a complete response, and 9 (43%) had a partial response, so the overall response rate was 48%. Of the remaining patients, 7 (33.3%) had stable disease, one patient did not respond, and three died while on therapy prior to response assessment. The median overall survival and time to progression were 21 months and 18 months, respectively. INTERPRETATION AND CONCLUSIONS: The median time to disease progression in patients with multiple myeloma who receive initial therapy with Thal/Dex and who do not undergo ASCT is 18 months.

Adult↗
PubMed2004

Incidence of multiple myeloma in Olmsted County, Minnesota: Trend over 6 decades.

BACKGROUND: Previous studies have indicated that the incidence and mortality rates for multiple myeloma have increased in the United States. The authors reported on the incidence of multiple myeloma in Olmsted County, Minnesota, between 1991 and 2001 and on trends in multiple myeloma incidence over the last 56 years. METHODS: Using the files of the Mayo Clinic and the Olmsted Medical Center (Rochester, MN), the authors identified all residents of Olmsted County who had multiple myeloma, suspected myeloma, or a related disorder. Reports of all laboratory determinations, in addition to autopsy findings and death certificates, were obtained. The criteria for the diagnosis of multiple myeloma have not changed during the last 6 decades. RESULTS: All but 1 of the 47 residents with multiple myeloma first diagnosed between 1991 and 2001 were recognized antemortem. Fifty-five percent had a previous monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, or solitary plasmacytoma before multiple myeloma was diagnosed. From 1991 to 2001, the overall annual incidence rate, age-adjusted to the 2000 U.S. population, was 4.3 per 100,000 (95% confidence interval, 3.0-5.5 per 100,000). Poisson regression analysis showed no statistically significant trend in Olmsted County incidence rates over 56 years. In similar fashion, the authors adjusted multiple myeloma incidence rates from nine other studies worldwide for which adequate data were available and documented similar findings in each case, except for one study that included patients with smoldering multiple myeloma. CONCLUSIONS: The overall incidence of multiple myeloma in Olmsted County, Minnesota, has not changed in almost 6 decades. The apparent increase in incidence elsewhere is unexplained but probably is attributable to improvements in diagnostic techniques, particularly in older patients.

Adolescent↗
PubMed2004

Fracture risk with multiple myeloma: a population-based study.

UNLABELLED: Pathologic fractures, especially of the axial skeleton, are extremely common in patients with multiple myeloma and cluster around the time of diagnosis. Osteoporotic fractures seem to be less of a problem in these patients. INTRODUCTION: It is generally believed that fractures are common in patients with multiple myeloma as a result of lytic bone lesions, generalized bone loss, and/or elevated bone turnover from excessive cytokine production, but the actual risk of pathologic versus osteoporotic fractures has not been quantified. MATERIALS AND METHODS: In a population-based retrospective cohort study, 165 Olmsted County, MN, residents with myeloma diagnosed from 1945 to 2001 (55% men; mean age, 70.7 +/- 11.1 years) were followed for 537 person-years. The relative risk of fractures was assessed by standardized incidence ratios (SIRs), and risk factors were evaluated in proportional hazards models. RESULTS: Altogether, 134 patients experienced 463 fractures. In the year before diagnosis, 16 times more fractures were observed than expected, mostly pathologic fractures of the vertebrae and ribs. Subsequently, there was a 9-fold increase in fracture risk. However, 69% of these fractures were pathologic, and another 11% were found incidentally on myeloma monitoring. With the latter two groups excluded, subsequent fracture risk was elevated 3-fold, with a 2-fold increase in the risk of an osteoporotic fracture. In multivariate analyses, the predictors of overall fracture risk were oral corticosteroid use and elevated serum calcium levels, whereas pathologic fractures were additionally predicted by use of chemotherapy. CONCLUSION: There is a dramatic increase in fractures around the time of diagnosis of myeloma, most of which are pathologic fractures. The most important predictor of overall fracture risk is oral corticosteroid use.

Adrenal Cortex Hormones↗
PubMed2004

Multiple myeloma.

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Antineoplastic Agents↗
PubMed2004

Serum cardiac troponins and N-terminal pro-brain natriuretic peptide: a staging system for primary systemic amyloidosis.

PURPOSE: Primary systemic amyloidosis (AL) is a multisystemic disorder resulting from an underlying plasma cell dyscrasia. There is no formal staging system for AL, making comparisons between studies and treatment centers difficult. Our group previously identified elevated serum cardiac troponin T (cTnT) as the most powerful predictor of overall survival. Others have reported that N-terminal pro-brain natriuretic peptide (NT-proBNP) is a valuable prognostic marker. We sought to develop a staging system for patients with AL. PATIENTS AND METHODS: Two hundred forty-two patients with newly diagnosed AL who were seen at the Mayo Clinic between April 1979 and November 2000, and who had echocardiograms and stored serum samples at presentation were eligible for this retrospective review. NT-proBNP measurements were performed on 242 patients in whom cTnT and cardiac troponin I (cTnI) had been previously run. Two prognostic models were designed using threshold values of NT-proBNP and either cTnT or cTnI (NT-proBNP < 332 ng/L, cTnT < 0.035 microg/L, and cTnI < 0.1 microg/L). Depending on whether NT-proBNP and troponin levels were both low, were high for only one level, or were both high, patients were classified as stage I, II, or III, respectively. RESULTS: Using the cTnT+NT-proBNP model 33%, 30%, and 37% of patients were stages I, II, and III, respectively, with median survivals of 26.4, 10.5, and 3.5 months, respectively. The alternate cTnI+NT-proBNP model predicted median survivals of 27.2, 11.1, and 4.1 months, respectively. CONCLUSION: Stratification of AL patients into three stages is possible with two readily available and reproducible tests setting the stage for more consistent and reliable cross comparisons of therapeutic outcomes.

Adult↗
PubMed2004

Thalidomid: current role in the treatment of non-plasma cell malignancies.

Thalidomide, initially introduced as a sedative, was withdrawn from the market in the early 1960s after it was found to be a teratogen. However, it later found use as an investigational agent in the treatment of erythema nodosum leprosum, oral ulcers, graft versus host disease, and wasting associated with the human immunodeficiency syndrome. Its antiangiogenic properties were recognized in the early 1990s during a period where the importance of angiogenesis became increasingly apparent as a critical step in the in the proliferation and spread of malignant neoplasms. This led to the evaluation of thalidomide as an antiangiogenic agent in the treatment of several cancers. Thalidomide has already become part of standard therapy for the treatment of patients with relapsed and refractory multiple myeloma. It has also been found to have varying degree of benefit in various other malignancies. Although more clinical trials are needed, Kaposi' s sarcoma and myelofibrosis represent other malignancies in which thalidomide has already demonstrated promising activity. The mechanism of action of thalidomide in cancer is still unclear, but do appear to be mediated by several other mechanisms in addition to its anti-angiogenic properties. This article reviews the current status of thalidomide for the treatment of non-plasma-cell malignancies.

Angiogenesis Inhibitors↗
PubMed2004

Bone marrow angiogenic ability and expression of angiogenic cytokines in myeloma: evidence favoring loss of marrow angiogenesis inhibitory activity with disease progression.

We compared the angiogenic potential of bone marrow plasma and the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and their receptors on plasma cells from patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), and newly diagnosed multiple myeloma (NMM). Cytokine and cytokine-receptor expression was studied by bone marrow immunohistochemistry, quantitative reverse transcription-polymerase chain reaction (RT-PCR) on sorted plasma cells, and quantitative Western blot analysis. Bone marrow angiogenic potential was studied using a human in vitro angiogenesis assay. The expression levels of VEGF, bFGF, and their receptors were similar among MGUS, SMM, and NMM. Sixty-one percent of NMM samples stimulated angiogenesis in the in vitro angiogenesis assay compared with SMM (0%) and MGUS (7%) (P <.001). Importantly, 63% of MGUS samples inhibited angiogenesis compared with SMM (43%) and NMM (4%) (P <.001). The inhibitory activity was heat stable, not overcome by the addition of VEGF, and corresponded to a molecular weight below 10 kd by size-exclusion chromatography. Our results suggest that increasing angiogenesis from MGUS to NMM is, at least in part, explained by increasing tumor burden rather than increased expression of VEGF/bFGF by individual plasma cells. The active inhibition of angiogenesis in MGUS is lost with progression, and the angiogenic switch from MGUS to NMM may involve a loss of inhibitory activity.

Bone Marrow↗
PubMed2004

Prognostication of survival using cardiac troponins and N-terminal pro-brain natriuretic peptide in patients with primary systemic amyloidosis undergoing peripheral blood stem cell transplantation.

Primary systemic amyloidosis (AL) is a fatal plasma cell disorder. Pilot data suggest survival is better in patients undergoing peripheral blood stem cell transplantation (PBSCT), but the selection process makes the apparent benefit suspect. We have reported that circulating cardiac biomarkers are the best predictors of survival outside of the transplantation setting. We now test whether cardiac troponins (cTnT and cTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are prognostic in transplant recipients. In 98 patients with AL undergoing PBSCT, serum cardiac biomarkers were measured (cTnT, 98 patients; cTnI, 65 patients; and NT-proBNP, 63 patients). Elevated levels of cTnT, cTnI, and NT-proBNP were present in 14%, 43%, and 48% of patients, respectively. At 20 months median follow-up, median survival has not been reached for patients with values below the thresholds; in patients with values above the thresholds, median survival is 26.1 months, 66.1 months, and 66.1 months, respectively. Our previously reported risk systems incorporating these markers were also prognostic, notably the cTnT/NT-proBNP staging. Using this system, 49%, 38%, and 13% of patients were in stage I, stage II, and stage III, respectively. Determining levels of circulating biomarkers may be the most powerful tool for staging patients with AL undergoing PBSCT.

Adult↗