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Angela Dispenzieri

Publications and source records attributed to Angela Dispenzieri.

At least 37 records · Page 2Linked to original sources
PubMed2006

Autologous stem cell transplantation and IgM amyloidosis.

High dose chemotherapy (HDC) followed by autologous stem cell transplant (ASCT) is an accepted form of treatment for patients with AL amyloidosis. The purpose of the current study is to review the outcomes of IgM AL amyloidosis patients treated with high dose chemotherapy and autologous stem cell transplant and compare them to the outcomes of all AL amyloidosis subtypes treated similarly. We retrospectively reviewed the pretransplant characteristics, conditioning regimens and response to transplant of all twelve IgM AL amyloidosis patients who were transplanted at the Mayo Clinic between May 1999 and August 2005. Transplant related mortality was low at 8%. The overall hematologic response rate was 89%. The organ response rate was 67%. Overall median survival has not been reached as eleven patients are still alive. IgM AL amyloidosis patients appear to have similar outcomes after HDC and ASCT as other subtypes of AL amyloidosis suggesting that this therapy is an acceptable form of treatment for patients with IgM amyloidosis, and should be considered as a first line treatment option.

Aged↗
PubMed2006

Natural history of thromboembolism in AL amyloidosis.

To determine the natural history of thromboembolism in patients with biopsy-proven AL amyloidosis, medical records of 2,132 patients evaluated at Mayo Clinic between 1975 and 2000 were reviewed. Forty patients (21 male) were found to have objectively documented thromboembolism. The median age was 65 years. Four patients had a monoclonal gammopathy of undetermined significance, 20 had an unspecified plasma cell proliferative disorder, 11 had multiple myeloma, and 1 had Waldenström macroglobulinemia. Twelve patients had cardiac amyloid, and 20 had renal amyloid. Neither the extent of the amyloid nor the type of monoclonal protein was predictive of the development of thromboembolic events. Thromboembolism preceded the diagnosis of AL amyloidosis in 11 patients, occurred at the time of diagnosis or within 1 month after diagnosis in 11 patients, and occurred 1 month or more after diagnosis in 18 patients. Twenty-nine patients (73%) had venous thrombosis and 11 (28%) had arterial thrombosis. Eight patients (20%) died within 1 month after the thrombotic event, and 18 (45%) died within 1 year. The development of thrombosis in patients with AL amyloidosis appears to predict significant mortality within the first month and year after the event.

Aged↗
PubMed2006

Identification of two groups of smoldering multiple myeloma patients who are either high or low producers of interleukin-1.

Interleukin-1beta (IL-1beta) is abnormally expressed by the plasma cells obtained from myeloma patients, and it is a potent inducer of the important myeloma growth factor, IL-6. We investigated whether levels of IL-1beta biologic activity might distinguish different groups of patients with smoldering multiple myeloma (SMM). We measured the ability of IL-6 production by bone marrow stromal cells to serve as a surrogate marker for IL-1beta biologic activity. Using this IL-1beta bioassay, we found that it is sensitive at < 1 pg/ml of recombinant IL-1beta and that IL-1beta biologic activity is detectable with either mature or pro-IL-1beta-transduced myeloma cell lines. Patients with active myeloma induced quantitatively higher levels of stromal cell IL-6 production when compared with those with monoclonal gammopathy of undetermined significance (MGUS). The bioassay distinguished two groups of SMM patients, those who were high producers, similar to patients with active MM, and those who were low producers, comparable to MGUS patients. IL-1 antagonists inhibited the paracrine IL-6 production by > or = 90% in the majority of patients with an elevated IL-6 level. Based on such studies, it may be possible to predict patients that will progress to active MM and to delay or prevent this progression with IL-1 antagonists.

Bone Marrow Cells↗
PubMed2006

Prognostic model for disease-specific and overall mortality in newly diagnosed symptomatic patients with Waldenstrom macroglobulinaemia.

We sought to define prognostic factors for survival in Waldenstrom macroglobulinaemia (WM). Of 585 patients diagnosed with WM and seen at Mayo Clinic between 1960 and 2001, 337 symptomatic patients met the inclusion criteria and were analysed for overall and disease-specific survival. The median survival from the time of diagnosis was 6.4 years. The median disease-specific survival was 11.2 years. Univariate analysis for overall survival identified the following adverse prognostic factors: age >65 years (P < 0.001), organomegaly (P < 0.001), elevated beta2-microglobulin (<0.001), anaemia (Hb < 10.0 g/dl) (P = 0.01), leucopenia (<4.0 x 10(9)/l) (P = 0.03), thrombocytopenia (<150 x 10(9)/l) (P = 0.01), serum albumin <40 g/l (P = 0.001), and quantitative IgM < 0.4 g/l (P = 0.04). On multivariate analysis, age >65 years and organomegaly were associated with poor prognosis. A prognostic model was built based on these two variables. Patients at high risk (1-2 risk factors, median survival 4.2 years) experienced worse survival than patients at low risk (0 risk factors, median survival 10.6 years), P < 0.001. The prognostic model was validated in 204 patients who were not included in the analysis cohort. Beta2-microglobulin > or =4 mg/l was associated with a threefold increase in the risk of death when added to the prognostic model. We describe a simple prognostic model for overall survival for newly diagnosed patients with WM.

Adult↗
PubMed2006

High-dose chemotherapy with autologous hematopoietic stem cell transplantation in patients with multiple myeloma.

Multiple myeloma, for all practical purposes, remains an incurable malignancy; however, 5-year survival has improved substantially during the past 30 years. A major contribution to improved outcome is the use of high-dose chemotherapy and stem cell transplantation. This multifaceted approach to therapy requires an understanding of appropriate induction therapy, techniques for stem cell mobilization, appropriate conditioning and supportive care. Also of importance are prognosis, features that predict outcome, the suitability of transplant candidates, and post-transplantation maintenance therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Cyclophosphamide mobilization does not improve outcome in patients receiving stem cell transplantation for multiple myeloma.

PURPOSE: Patients with multiple myeloma who undergo autologous stem cell transplantation (ASCT) and exhibit a complete response (CR) have a superior overall survival and time to progression (TTP). High-dose cyclophosphamide is often used before ASCT for mobilization of hematopoietic stem cells. We hypothesized that cyclophosphamide might further improve CR rates in patients undergoing ASCT. We searched the Mayo Clinic myeloma transplantation database for patients who had stem cell mobilization with hematopoietic growth factor alone or cyclophosphamide and growth factor. The impact of cyclophosphamide on CR rates and TTP was evaluated. PATIENTS AND METHODS: A cohort of 201 patients was identified: 127 mobilized with cyclophosphamide and growth factor and 74 with growth factor alone. There were no statistically significant differences between the 2 cohorts in regard to age, sex, b2-microglobulin level, plasma cell labeling index, cytogenetics, conditioning regimen, or disease status at time of transplantation. RESULTS: Complete response rates were 37.4% and 41.3% (P = 0.6115) for patients mobilized with cyclophosphamide combined with growth factor and growth factor alone, respectively, and TTPs were 19.9 months and 20.9 months (P = 0.59). In a multivariate analysis for TTP, cytogenetics and CR rates were the only independent variables (P = 0.0012 and P < 0.0001, respectively). CONCLUSION: We conclude that high-dose cyclophosphamide does not increase overall CR rates or improve TTP for patients with myeloma undergoing ASCT.

Adult↗
PubMed2006

Response to rituximab in patients with type II cryoglobulinemia.

Type II cryoglobulinemia (CG) is a heterogeneous, generally indolent disorder caused by a monoclonal antibody with activity against polyclonal antibodies and is commonly associated with hepatitis C, lymphoproliferative disorders (LPDs), or autoimmune diseases. It can lead to substantial morbidity, including renal failure, cutaneous ulcers, or neuropathy. Medical records were reviewed for 8 patients with previously treated symptomatic CG who were part of a prospectively held dysproteinemia database. Patients subsequently received 14 total courses of rituximab treatment (standard infusion, 375 mg/m2 for 4 or 8 doses) between February 1999 and March 2005. One patient had essential CG, and 1 had Gaucher disease with hypersplenism. Six patients had an LPD, and 4 of them had concomitant disorders (2 with hepatitis C and 2 with Sjogren syndrome). Treatment indications included purpura, LPD, cutaneous ulcers, and renal failure. Clinical improvement was evaluated by improved cryocrit, total complement, C4, and rheumatoid factor. Six patients had some clinical improvement. Cutaneous manifestations were the most responsive; renal disease and lymphoma were more refractory. Laboratory values showed improvement after 7 of 12 available treatment courses. No adverse reactions were noted. Overall, rituximab appears to be a safe and effective therapy.

Antibodies, Monoclonal↗
PubMed2006

Elimination of the need for urine studies in the screening algorithm for monoclonal gammopathies by using serum immunofixation and free light chain assays.

OBJECTIVE: To determine the relative diagnostic contribution of urine assays as part of the screening algorithm for monoclonal gammopathies. PATIENTS AND METHODS: We identified 428 patients with a monoclonal gammopathy and monoclonal urinary protein at initial diagnosis of plasma cell dyscrasia who had also undergone serum immunofixation and serum free light chain quantitation within 30 days of diagnosis. The laboratory results for serum protein electrophoresis, serum immunofixation, serum free light chain, urine protein electrophoresis, and urine immunofixation were reviewed. RESULTS: The patients had diagnoses of multiple myeloma, primary amyloid, monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, solitary plasmacytomas, and other less frequently detected monoclonal gammopathies. All 428 had a monoclonal urine protein, 85.7% had an abnormal serum free light chain kappa/lambda ratio, 80.8% had an abnormal serum protein electrophoresis, and 93.5% had an abnormal serum immunofixation result. All 3 serum assays were normal in only 2 patients, 1 of whom had monoclonal gammopathy of undetermined significance (idiopathic Bence Jones proteinuria) and 1 whose urine sample contained an intact monoclonal immunoglobulin but whose serum and subsequent urine samples showed no evidence of a monoclonal gammopathy. CONCLUSION: Discontinuation of urine studies and reliance on a diagnostic algorithm using only serum studies (protein electrophoresis, immunofixation, and free light chain quantitation) missed 2 (0.5%) of the 428 monoclonal gammopathies with urinary monoclonal proteins, and these 2 cases required no medical intervention.

Algorithms↗
PubMed2006

Monoclonal gammopathy of undetermined significance, Waldenström macroglobulinemia, AL amyloidosis, and related plasma cell disorders: diagnosis and treatment.

The spectrum of plasma cell disorders is broad. Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma are asymptomatic disorders characterized by monoclonal plasma cell proliferation in the bone marrow in the absence of end-organ damage. Waldenström macroglobulinemia typically involves an ontogenically less mature lymphoplasmacytic bone marrow cell and is characterized by secretion of a monoclonal IgM protein. Solitary plasmacytoma is the only known potentially curable plasma cell disorder. Finally, AL (immunoglobulin light chain) amyloidosis and POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome are disorders characterized by low tumor burden but profound multisystemic disease. Updated diagnostic criteria for these disorders, risk stratification models to determine prognosis, and the current management of these diverse entitles are discussed in this review.

Amyloidosis↗
PubMed2006

Mayo clinic consensus statement for the use of bisphosphonates in multiple myeloma.

Bisphosphonates are effective in the prevention and treatment of bone disease in multiple myeloma (MM). Osteonecrosis of the jaw is Increasingly recognized as a serious complication of long-term bisphosphonate therapy. Issues such as the choice of bisphosphonate and duration of therapy have become the subject of intense debate given patient safety concerns. We reviewed available data concerning the use of bisphosphonates in MM. Guidelines for the use of bisphosphonates in MM were developed by a multidisciplinary panel consisting of hematologists, dental specialists, and nurses specializing in the treatment of MM. We conclude that intravenous pamidronate and intravenous zoledronic acid are equally effective and superior to placebo in reducing skeletal complications. Pamidronate is favored over zoledronic acid until more data are available on the risk of complications (osteonecrosis of the jaw). We recommend discontinuing bisphosphonates after 2 years of therapy for patients who achieve complete response and/or plateau phase. For patients whose disease is active, who have not achieved a response, or who have threatening bone disease beyond 2 years, therapy can be decreased to every 3 months. These guidelines were developed in the Interest of patient safety and will be reexamined as new data emerge regarding risks and benefits.

Bone Density Conservation Agents↗
PubMed2005

Clinical implication of centrosome amplification in plasma cell neoplasm.

The mechanisms underlying aneuploidy in multiple myeloma (MM) are unclear. Centrosome amplification has been implicated as the cause of chromosomal instability in a variety of tumors and is a potential mechanism causing aneuploidy in MM. Using immunofluorescent (IF) staining, centrosome amplification was detected in 67% of monoclonal gammopathies, including monoclonal gammopathy of undetermined significance (MGUS). We also investigated the gene expression of centrosome proteins. Overall, gene expression data correlated well with IF-detected centrosome amplification, allowing us to derive a gene expression-based centrosome index (CI) as a surrogate for centrosome amplification. Clinically, MM patients with high CI (> 4) are associated with poor prognostic genetic and clinical subtypes (chromosome 13 deletion, t(4; 14), t(14;16), and PCLI > 1%, P < .05) and are shown here to have short survival (11.1 months versus 39.1 months, P < .001). On multivariate regression, a high CI is an independent prognostic factor. Given that centrosome amplification is already observed in MGUS and probably integral to early chromosomal instability and myeloma genesis, and patients with more extensive centrosome amplification have shorter survival, the mechanisms leading to centrosome amplification should be investigated because these may offer new avenues for therapeutic intervention.

Adult↗
PubMed2005

Flow cytometric detection of circulating myeloma cells before transplantation in patients with multiple myeloma: a simple risk stratification system.

Detection of circulating myeloma cells (CMCs) by flow cytometry in patients with multiple myeloma (MM) indicates active disease. We hypothesized that detection of CMCs at the time of stem-cell collection prior to autologous stem-cell transplantation (ASCT) identifies patients at high risk of rapid progression. A cohort of patients undergoing ASCT was identified. CMCs were determined by gating on CD38+/CD45- cells using flow cytometry. The impact of CMCs on overall survival (OS) and time to progression (TTP) was evaluated in univariate and multivariate analyses. Of 246 patients undergoing ASCT, 95 had CMCs. Complete response (CR) rates after transplantation were 32% and 36% for patients with and without CMCs, respectively (P = .50). OSs were 33.2 and 58.6 months (P = .01) whereas TTPs were 14.1 and 22 months, respectively (P = .001). On multivariate analysis, CMCs remained independent of cytogenetics and disease status at time of transplantation (P = .03). CMCs and cytogenetics were combined in a new scoring system. Patients with neither, one, or both parameters had a median OS of 55, 48, and 21.5 months and a median TTP of 22, 15.4, and 6.5 months, respectively. CMCs at the time of ASCT is an independent prognostic factor and in combination with cytogenetics provides a powerful scoring system that stratifies patients and guides management.

Adult↗
PubMed2005

Two-dimensional acoustic pattern derived strain parameters closely correlate with one-dimensional tissue Doppler derived strain measurements.

BACKGROUND: Two-dimensional strain echocardiography (2D-SE) calculates tissue velocities via frame-to-frame tracking of unique acoustic markers within the image and provides strain parameters in two dimensions. Novel 2D-SE software allows semi-automated strain measurements and increased averaging capabilities optimizing signal-noise ratio. AIM: We tested whether 2D-SE and the currently used and well-validated tissue Doppler derived strain echocardiography (TD-SE) yield similar information in the clinical setting. METHODS AND RESULTS: We performed 2D-SE and TD-SE on 17 patients with amyloid cardiomyopathy and 10 age-matched healthy volunteers. Single walls from standard apical views (2- and 4-chamber) were acquired at high frame rates ( approximately 200fps). Offline analysis was performed by observers blinded to clinical data using the EchoPAC program with custom 2D-SE software. Longitudinal strain rate and strain from the basal, mid and apical segments of the septal and lateral walls were determined by each method (TD-SE and 2D-SE). Ejection fraction was >0.55 in healthy volunteers and ranged from 0.30 to 0.80 in cardiomyopathy group. A total of 54 walls (162 segments) were examined. Acceptable quality strain data was available in 92% and 85% segments by 2D-SE and TD-SE, respectively. Two-dimensional strain echocardiography values correlated closely with TD-SE values (r=0.94 and 0.96 for strain rate and strain, respectively). CONCLUSIONS: Deformation analysis by 2D-SE is feasible in a clinical setting and 2D-SE values correlate closely with TD-SE measurements over a wide range of global systolic function. Two-dimensional strain echocardiography may help to facilitate the routine clinical implementation of deformation analysis.

Acoustics↗
PubMed2005

Combination therapy with lenalidomide plus dexamethasone (Rev/Dex) for newly diagnosed myeloma.

We report the results of a phase 2 trial using lenalidomide plus dexamethasone (Rev/Dex) as initial therapy for myeloma. Thirty-four patients were enrolled. Lenalidomide was given orally 25 mg daily on days 1 to 21 of a 28-day cycle. Dexamethasone was given orally 40 mg daily on days 1 to 4, 9 to 12, and 17 to 20 of each cycle. Objective response was defined as a decrease in serum monoclonal protein level by 50% or greater and a decrease in urine M protein level by at least 90% or to a level less than 200 mg/24 hours, confirmed by 2 consecutive determinations at least 4 weeks apart. Thirty-one of 34 patients achieved an objective response, including 2 (6%) achieving complete response (CR) and 11 (32%) meeting criteria for both very good partial response and near complete response, resulting in an overall objective response rate of 91%. Of the 3 remaining patients not achieving an objective response, 2 had minor response (MR) and one had stable disease. Forty-seven percent of patients experienced grade III or higher nonhematologic toxicity, most commonly fatigue (15%), muscle weakness (6%), anxiety (6%), pneumonitis (6%), and rash (6%). Rev/Dex is a highly active regimen with manageable side effects in the treatment of newly diagnosed myeloma.

Adult↗
PubMed2005

Prognostic value of circulating plasma cells in monoclonal gammopathy of undetermined significance.

PURPOSE: Monoclonal gammopathy of undetermined significance (MGUS) progresses to multiple myeloma or another related plasma cell disorder (PCD) at a rate of approximately 1% per year. Identification of patients with MGUS at high risk of progression will allow development of preventive strategies. We studied the prognostic value of circulating plasma cells (PCs) in patients with MGUS to predict progression. PATIENTS AND METHODS: Patients were eligible for this retrospective analysis if they were seen at the Mayo Clinic between 1984 and 1997, were diagnosed with MGUS, and had an analysis of the peripheral blood for circulating PCs by the slide-based immunofluorescence method. Patients were observed for progression to another PCD. RESULTS: Three hundred twenty-five patients were eligible and 63 (19%) had circulating PCs. Patients with circulating PCs were twice as likely (hazard ratio, 2.1) to experience progression to another PCD (most commonly myeloma), compared with those without circulating PCs (95% CI, 1.1 to 4.3; P = .03). In patients with circulating PCs, the median progression-free survival was 138 months compared with a median not yet reached for those without circulating PCs (P = .028). The median overall survival also was shorter for those with circulating PCs. Other factors with prognostic value were high levels of M protein and non-immunoglobulin G heavy-chain type. CONCLUSION: The presence of circulating PCs, especially when combined with other known prognostic factors such as M protein concentration and immunoglobulin isotype, identify a group of individuals with MGUS at higher risk of progression to overt multiple myeloma.

Adolescent↗
PubMed2005

Excessive fluid accumulation during stem cell mobilization: a novel prognostic factor of first-year survival after stem cell transplantation in AL amyloidosis patients.

High-dose melphalan followed by stem cell transplantation (HDM-SCT) has become the treatment of choice for patients with immunoglobulin light chain amyloidosis (AL). Unfortunately, treatment mortality can be excessive in certain subpopulations. We have noted that patients who gained more than 2% body weight during mobilization had a poorer outcome following HDM-SCT. Excluding 2 patients for lack of weight record and denial of consent, 126 patients between July 1997 and June 2003 were retrospectively studied. Weight increased more than 2.0% during mobilization in 51.6% of the patients. Patients who accumulated more than 2.0% tended to have more proteinuria, more organs involved, lower serum albumin, more diuretic use, and dosage adjustment during mobilization. First-year mortality was significantly higher in those with more than 2% weight gain (33.9% versus 9.8%, P = .002). Multivariate analysis showed weight gain, glomerular filtration rate, and septal thickness to be independent predictors of first-year mortality. The increase in mortality was noted even after the excess weight was diuresed prior to conditioning. The impact on mortality dissipated after the first year. Weight gain during mobilization appears to be a new marker of adverse outcome following HDM-SCT. Better prognostication may improve the treatment mortality rate of these patients.

Adult↗
PubMed2005

Clinical implications of t(11;14)(q13;q32), t(4;14)(p16.3;q32), and -17p13 in myeloma patients treated with high-dose therapy.

Fluorescence in situ hybridization (FISH) is more sensitive than conventional cytogenetics for recognizing chromosomal changes. Several FISH-detected abnormalities have been associated with inferior prognosis, including deletion of chromosomes 17 and 13 (Delta13) and t(4;14)(p16.3;q32). We analyzed the prognostic value of FISH testing in 238 patients who received high-dose therapy between January 1990 and September 2001. All patients had pretransplantation cytoplasmic immunoglobulin FISH done on cytospin slides from bone marrow aspirates for t(11;14), t(4;14), and -17(p13.1) (TP53). Time to progression and overall survival were significantly shorter for patients with t(4;14) and those with -17(p13.1) but were not affected by t(11;14). Overall survival was significantly shorter for patients with both t(4;14) and Delta13 abnormalities than for those with Delta13 alone (26.8 vs 18.8 months). In a multivariable analysis of the effect of Delta13 and t(4;14), the risk ratio for t(4;14) was greater than for Delta13 (2.6 vs 1.5). For high-dose therapy patients, -17(p13) and t(4;14) have clinical importance for estimating time to progression and overall survival. The presence of t(4;14) identifies a subset of patients whose time to progression is only 8.2 months. These patients receive minimal benefit from autologous stem cell transplantation and are candidates for novel therapeutic approaches.

Adult↗