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1.
Ann Oncol ; 28(2): 228-245, 2017 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-27864218

RESUMEN

Background: Therapeutic advancements following the introduction of autologous stem cell transplantation and 'novel' agents have significantly improved clinical outcomes for patients with multiple myeloma (MM). Increased life expectancy, however, has led to renewed concerns about the long-term risk of second primary malignancies (SPMs). This review outlines the most up-to-date knowledge of possible host-, disease-, and treatment-related risk factors for the development of SPMs in patients with MM, and provides practical recommendations to assist physicians. Design: A Panel of International Myeloma Working Group members reviewed the most relevant data published in the literature as full papers, or presented at meetings of the American Society of Clinical Oncology, American Society of Hematology, European Hematology Association, or International Myeloma Workshops, up to June 2016. Here, we present the recommendations of the Panel, based on this literature review. Results: Overall, the risk of SPMs in MM is low, multifactorial, and partially related to the length of patients' survival and MM intrinsic susceptibility. Studies suggest a significantly increased incidence of SPMs when lenalidomide is administered either following, or concurrently with, oral melphalan. Increased SPM incidence has also been reported with lenalidomide maintenance following high-dose melphalan, albeit to a lesser degree. In both cases, the risk of death from MM was significantly higher than the risk of death from SPMs, with lenalidomide possibly providing a survival benefit. No increase in SPM incidence was reported with lenalidomide plus dexamethasone (without melphalan), or with bortezomib plus oral melphalan, dexamethasone, or thalidomide. Conclusion: In general, the risk of SPMs should not alter the current therapeutic decision-making process in MM. However, regimens such as lenalidomide plus dexamethasone should be preferred to prolonged exposure to lenalidomide plus oral melphalan. SPM risk should be carefully discussed with the patient in the context of benefits and risks of different treatment options.


Asunto(s)
Mieloma Múltiple/terapia , Neoplasias Primarias Secundarias/etiología , Humanos , Incidencia , Mieloma Múltiple/epidemiología , Mieloma Múltiple/patología , Neoplasias Primarias Secundarias/epidemiología , Factores de Riesgo
2.
J Intern Med ; 281(6): 611-619, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-28439924

RESUMEN

BACKGROUND: Data on the effect of systemic immunoglobulin light chain amyloidosis (AL amyloidosis) on thyroid function are limited. OBJECTIVE: To assess the prevalence of hypothyroidism in AL amyloidosis patients and determine its predictors. METHODS: 1142 newly diagnosed AL amyloidosis patients were grouped based on the thyroid-stimulating hormone (TSH) measurement at diagnosis: hypothyroid group (TSH above upper normal reference; >5 mIU L-1 ; n = 217, 19% of study participants) and euthyroid group (n = 925, 81%). Predictors for hypothyroidism were assessed in a binary multivariate model. Survival between groups was compared using the log-rank test and a multivariate analysis. RESULTS: Patients with hypothyroidism were older, more likely to present with renal and hepatic involvement and had a higher light chain burden compared to patients in the euthyroid group. Higher proteinuria in patients with renal involvement and lower albumin in patients with hepatic involvement were associated with hypothyroidism. In a binary logistic regression model, age ≥65 years, female sex, renal involvement, hepatic involvement, kappa light chain restriction and amiodarone use were independently associated with hypothyroidism. Ninety-three per cent of patients in the hypothyroid group with free thyroxine measurement had normal values, consistent with subclinical hypothyroidism. Patients in the hypothyroid group had a shorter survival compared to patients in the euthyroid group (4-year survival 36% vs 43%; P = 0.008), a difference that was maintained in a multivariate analysis. CONCLUSION: A significant proportion of patients with AL amyloidosis present with hypothyroidism, predominantly subclinical, which carries a survival disadvantage. Routine assessment of TSH in these patients is warranted.


Asunto(s)
Amiloidosis/epidemiología , Hipotiroidismo/epidemiología , Anciano , Amiloidosis/mortalidad , Anticuerpos/sangre , Comorbilidad , Femenino , Terapia de Reemplazo de Hormonas , Humanos , Hipotiroidismo/sangre , Hipotiroidismo/tratamiento farmacológico , Hipotiroidismo/etiología , Yoduro Peroxidasa/inmunología , Enfermedades Renales/epidemiología , Hepatopatías/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Análisis de Supervivencia , Hormonas Tiroideas/uso terapéutico , Tirotropina/sangre , Tiroxina/sangre
4.
Blood Cancer J ; 11(6): 120, 2021 06 24.
Artículo en Inglés | MEDLINE | ID: mdl-34168119

RESUMEN

Soluble BCMA (sBCMA) levels are elevated in monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). However, the association between sBCMA levels and prognosis in MGUS and SMM has not been studied. We retrospectively analyzed sBCMA levels in stored samples from 99 MGUS and 184 SMM patients. Baseline sBCMA levels were significantly higher in MGUS and SMM patients progressing to MM during clinical follow up. When stratified according to the median baseline sBCMA level for each cohort, higher levels were associated with a shorter PFS for MGUS (HR 3.44 comparing sBCMA ≥77 vs <77 ng/mL [95% CI 2.07-5.73, p < 0.001] and SMM (HR 2.0 comparing sBCMA ≥128 vs <128 ng/mL, 95% 1.45-2.76, p < 0.001) patients. The effect of sBCMA on PFS was similar even after adjusting for the baseline MGUS or SMM risk stratification. We evaluated paired serum samples and found that sBCMA increased significantly in MGUS and SMM patients who eventually progressed to MM, whereas among MGUS non-progressors the sBCMA level remained stable. While our results require independent validation, they suggest that sBCMA may be a useful biomarker to identify MGUS and SMM patients at increased risk of progression to MM independent of the established risk models.


Asunto(s)
Antígeno de Maduración de Linfocitos B/sangre , Gammopatía Monoclonal de Relevancia Indeterminada , Proteínas de Neoplasias/sangre , Mieloma Múltiple Quiescente , Anciano , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Gammopatía Monoclonal de Relevancia Indeterminada/sangre , Gammopatía Monoclonal de Relevancia Indeterminada/mortalidad , Valor Predictivo de las Pruebas , Mieloma Múltiple Quiescente/sangre , Mieloma Múltiple Quiescente/mortalidad , Tasa de Supervivencia
5.
Blood Cancer J ; 11(12): 196, 2021 12 07.
Artículo en Inglés | MEDLINE | ID: mdl-34876555

RESUMEN

Belantamab mafodotin is a highly selective targeted therapy for multiple myeloma. It targets the B cell maturation antigen (BCMA) on plasma cells and showed promising results in several randomized clinical trials. We report the outcomes of 36 patients treated at Mayo Clinic. Our cohort received a median of eight prior lines of therapy. Six patients received belantamab in combination with other medications (pomalidomide, cyclophosphamide, thalidomide), 13 patients (36%) were 70 years or older, two patients had a creatinine of >2.5 mg/dL, and one patient was on dialysis. All three patients with renal failure received full dose belantamab. Chimeric antigen receptor (CAR-T) therapy was used prior to belantamab in seven patients and none of them responded to belantamab therapy. The overall response rate (ORR) was 33% (CR 6%, VGPR 8%, PR 19%), like the ORR reported in the DREAMM-2 trial. Keratopathy developed in 16 patients (43%), grade 1 in six patients, grade 2 in seven patients, and grade 3 in three patients. Eight percent discontinued therapy due to keratopathy. The median PFS and OS was 2 months and 6.5 months, respectively.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/efectos adversos , Antineoplásicos Inmunológicos/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento
6.
Leukemia ; 34(10): 2749-2753, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32594098

RESUMEN

Our group previously demonstrated that M-protein light chain (LC) glycosylation can be detected on routine MASS-FIX testing. Glycosylation is increased in patients with immunoglobulin LC amyloidosis (AL) and rarely changes over the course of a patient's lifetime. To determine the rates of progression to AL and other plasma cell disorders (PCDs), we used residual serum samples from the Olmsted monoclonal gammopathy of undetermined significance (MGUS) screening cohort. Four-hundred and fourteen patients with known MGUS were tested by MASS-FIX, and 25 (6%) were found to have glycosylated LCs. With a median follow-up of surviving patients of 22.2 years, the 20-year progression rates to a malignant PCD were 67% (95% CI 29%, 84%) and 13% (95% CI 9%, 18%) for patients with and without glycosylated LCs, respectively. The risk of progression was independent of Mayo MGUS risk score. The respective rates of progression to AL at 20 years were 21% (95% CI 0.0%, 38%) and 3% (95% CI 0.6%, 5.5%). In summary, monoclonal LC glycosylation is a potent risk factor for progression to AL, myeloma, and other PCDs, an observation which could lead to earlier diagnoses and potentially reduced morbidity and mortality.


Asunto(s)
Biomarcadores , Cadenas Ligeras de Inmunoglobulina/metabolismo , Gammopatía Monoclonal de Relevancia Indeterminada/diagnóstico , Gammopatía Monoclonal de Relevancia Indeterminada/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Glicosilación , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Gammopatía Monoclonal de Relevancia Indeterminada/sangre , Proteínas de Mieloma/metabolismo , Pronóstico
8.
Kidney Int ; 73(11): 1282-8, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18385667

RESUMEN

Cast nephropathy is the most common cause of renal disease in multiple myeloma, however, treatment with plasma exchange remains controversial even after 3 randomized controlled studies. We sought to determine the importance of diagnostic confirmation and goal directed therapy in the treatment of cast nephropathy in forty patients with confirmed multiple myeloma and renal failure who underwent plasma exchange. A positive renal response was defined as a decrease by half in the presenting serum creatinine and dialysis independence. No baseline differences were noted between eventual renal responders and non-responders. Three quarters of the patients with biopsy proven cast nephropathy resolved their renal disease when the free light chains present in the serum were reduced by half or more but there was no significant response when the reduction was less. The median time to a response was about 2 months. In patients without cast nephropathy, renal recovery occurred despite reductions in free light chain levels of the serum. No association was found between free light chains in the serum, urinary monoclonal proteins, overall proteinuria and cast nephropathy. We found that the relationship between renal recovery and free light chain reduction was present only in patients with biopsy proven cast nephropathy showing the importance of extracorporeal light chain removal in this disease.


Asunto(s)
Cadenas Ligeras de Inmunoglobulina/sangre , Neoplasias Renales/complicaciones , Mieloma Múltiple/complicaciones , Intercambio Plasmático , Insuficiencia Renal/diagnóstico , Insuficiencia Renal/terapia , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales/orina , Femenino , Humanos , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Mieloma Múltiple/patología , Insuficiencia Renal/etiología , Estudios Retrospectivos , Resultado del Tratamiento
9.
Leukemia ; 21(1): 169-74, 2007 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-17051241

RESUMEN

CD307 is a differentiation antigen expressed in B-lineage cells. One soluble and two membrane-bound forms have been predicted and an enzyme-linked immunosorbent assay (ELISA) for soluble CD307 established. Our goal was to determine if CD307 is expressed on the surface of cells from patients with multiple myeloma (MM), chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL) and other B-cell malignancies and if soluble CD307 levels are elevated in the blood of patients with these B-cell malignancies. Cells and blood were collected from patients. Expression of CD307 was measured by flow cytometry and blood levels of soluble CD307 by ELISA. High soluble CD307 levels were detected in 21/43 (49%) of patients with MM, 36/46 (78%) with CLL and 9/24 (38%) with MCL. Soluble CD307 levels correlated with plasma cell percentages in bone marrow aspirates in MM and total white blood cells in CLL. CD307 on the cell membrane was detected by flow cytometry in 8/8 MM, 23/29 CLL and 4/5 MCL samples. Because CD307 is present on malignant cells from patients with MM, CLL and MCL, CD307 may be a useful therapeutic target for the treatment of these diseases.


Asunto(s)
Biomarcadores de Tumor , Leucemia Linfocítica Crónica de Células B/sangre , Linfoma de Células del Manto/sangre , Mieloma Múltiple/sangre , Receptores de Superficie Celular/metabolismo , Adolescente , Adulto , Anciano , Linfocitos B/metabolismo , Linfocitos B/patología , Femenino , Citometría de Flujo , Humanos , Masculino , Persona de Mediana Edad , Receptores Fc
10.
Leukemia ; 21(3): 529-34, 2007 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-17230230

RESUMEN

Clinical outcomes for multiple myeloma (MM) are highly heterogeneous and it is now clear that pivotal genetic events are the primary harbingers of such variation. These findings have broad implications for counseling, choice of therapy and the design and interpretation of clinical investigation. Indeed, as in acute leukemias and non-hodgkins lymphoma, we believe it is no longer acceptable to consider MM a single disease entity. As such, the accurate diagnosis of MM subtypes and the adoption of common criteria for the identification and stratification of MM patients has become critical. Herein, we provide a consensus high-risk definition and offer practical guidelines for the adoption of routine diagnostic testing. Although acknowledging that more refined classifications will continue to be developed, we propose that the definition of high-risk disease (any of the t(4;14), t(14;16), t(14;20), deletion 17q13, aneuploidy or deletion chromosome 13 by metaphase cytogenetics, or plasma cell labeling index >3.0) be adopted. This classification will identify most of the 25% of MM patients for whom current therapies are inadequate and for whom investigational regimens should be vigorously pursued. Conversely, the 75% of patients remaining have more favorable outcomes using existing - albeit non-curative - therapeutic options.


Asunto(s)
Ensayos Clínicos como Asunto/normas , Mieloma Múltiple/clasificación , Antineoplásicos/uso terapéutico , Cromosomas Humanos/genética , Cromosomas Humanos/ultraestructura , Consejo , Toma de Decisiones , Pruebas Diagnósticas de Rutina , Diseño de Fármacos , Marcación de Gen , Terapia Genética , Genotipo , Humanos , Mieloma Múltiple/genética , Mieloma Múltiple/terapia , Células Plasmáticas/patología , Pronóstico , Riesgo , Medición de Riesgo , Translocación Genética , Resultado del Tratamiento , Carga Tumoral
12.
Leukemia ; 32(1): 131-138, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-28655925

RESUMEN

Translocation (11;14) on interphase fluorescent in situ hybridization in plasma cells is regarded as a standard risk prognostic marker in multiple myeloma based on studies conducted before introduction of current therapies. We identified 365 patients with t(11;14), and 730 matched controls:132 patients with non-(11;14) translocations and 598 patients with no chromosomal translocation. The median progression-free survival for the three groups were 23.0 (95% confidence interval (CI), 20.8-27.6), 19.0 (95% CI, 15.8-22.7) and 28.3 (95% CI, 25.7-30.6) months, respectively (P<0.01). The median overall survival (OS) for t(11;14), non-(11;14) translocation and no-translocation groups were 74.4 (95% CI, 64.8-89.3), 49.8 (95% CI, 40.0-60.6) and 103.6 (95% CI, 85.2-112.3) months, respectively (P<0.01). Excluding those with 17p abnormality, the median OS in the three groups were 81.7 (95% CI, 67.0-90.7), 58.2 (95% CI, 47.0-76.4) and 108.3 (95% CI, 92.4-140.1) months, respectively (P<0.01). The above relationship held true in patients with age <65 years, international staging system (ISS) I/II stage or those who received novel agent-based induction. Advanced age (hazard ratio (HR): 1.98), 17p abnormality (HR: 2.2) and ISS III stage (HR: 1.59) at diagnosis predicted reduced OS in patients with t(11;14). These results suggest that outcomes of t(11;14) MM are inferior to other standard risk patients.


Asunto(s)
Cromosomas Humanos/genética , Mieloma Múltiple/genética , Mieloma Múltiple/patología , Adulto , Anciano , Anciano de 80 o más Años , Aberraciones Cromosómicas , Femenino , Humanos , Hibridación Fluorescente in Situ/métodos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias/métodos , Pronóstico , Supervivencia sin Progresión , Translocación Genética/genética , Adulto Joven
13.
Leukemia ; 32(3): 719-728, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-28860655

RESUMEN

Despite therapeutic advances, multiple myeloma remains incurable, with limited options for patients with refractory disease. We conducted a large, multi-cohort clinical trial testing various doses and treatment schedules of pomalidomide and dexamethasone (Pom/dex) in patients with refractory multiple myeloma. Overall, 345 patients were enrolled to six cohorts based on number and type of prior lines of therapy, pomalidomide dose and schedule. Median prior lines of therapy were three with near universal prior exposure to proteasome inhibitors and/or immunomodulatory drugs. A confirmed response rate of 35% was noted for all cohorts (range 23-65%) with higher responses in cohorts with fewer prior lines of therapy. Median time to confirmed response was ⩽2 months and the longest progression-free survival and overall survival seen in any cohort were 13.1 and 47.9 months, respectively. Observed adverse reactions were as expected, with myelosuppression and fatigue being the most common hematologic and non-hematologic adverse events (AEs), respectively. Longer durations of treatment and response, higher response rates and fewer AEs were noted with the 2 mg pomalidomide dose. This is the longest follow-up data for Pom/dex in refractory multiple myeloma and will help shape the real-world utilization of this regimen.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resistencia a Antineoplásicos , Mieloma Múltiple/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Biomarcadores de Tumor , Dexametasona/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/genética , Mieloma Múltiple/mortalidad , Retratamiento , Análisis de Supervivencia , Talidomida/administración & dosificación , Talidomida/análogos & derivados , Resultado del Tratamiento
14.
Leukemia ; 32(3): 729-735, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-28919633

RESUMEN

Hematologic response criteria in light chain (AL) amyloidosis require the difference in involved and uninvolved free light chains (dFLC) to be at least 5 mg/dl. We describe the clinical presentation and outcomes of newly diagnosed amyloidosis patients with dFLC <5 mg/dl (non-evaluable dFLC; 14%, n=165) compared with patients with dFLC ⩾5 mg/dl (evaluable dFLC; 86%, n=975). Patients with non-evaluable dFLC had less cardiac involvement (40% vs 80%, P<0.001), less liver involvement (11% vs 17%, P=0.04) and a trend toward less gastrointestinal involvement (18% vs 25%, P=0.08). However, significantly higher renal involvement (72% vs 56%, P=0.0002) was observed in the non-evaluable dFLC cohort. Differences in treatment patterns were observed, with 51% of treated patients undergoing upfront stem cell transplantation in the non-evaluable cohort compared with 28% in the evaluable dFLC group (P<0.001). Progression-free survival (61 vs 13 months, P<0.001) and overall survival (OS; 101 vs 29 months, P<0.001) were significantly longer in the non-evaluable dFLC cohort. Normalization of involved light chain levels and decrease in dFLC <1 mg/dl (baseline at least 2 mg/dl) were predictive of OS and associated with better dialysis-free survival and may be used for response assessment in patients with non-evaluable FLC levels.


Asunto(s)
Cadenas Ligeras de Inmunoglobulina/sangre , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/sangre , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/diagnóstico , Fenotipo , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores , Terapia Combinada , Femenino , Humanos , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/mortalidad , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/terapia , Masculino , Persona de Mediana Edad , Especificidad de Órganos , Pronóstico , Modelos de Riesgos Proporcionales , Evaluación de Síntomas , Resultado del Tratamiento
15.
Bone Marrow Transplant ; 40(12): 1115-21, 2007 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-17680019

RESUMEN

Multiple myeloma (MM) is a disease of the elderly with a median age at diagnosis of 67 years in a referral population. High-dose chemotherapy (HDT) and autologous stem cell transplantation has been shown to improve survival in patients with MM in randomized trials and remains the preferred option for eligible patients. However, the randomized clinical trials demonstrating an advantage for HDT included only patients younger than 65 years and evidence supporting its role for the elderly patients has been based on retrospective reviews. The introduction of thalidomide, lenalidomide and bortezomib has changed the paradigm for treatment of myeloma and improved the outcome for these patients. Several ongoing clinical trials are evaluating the role of these novel agents in this population, specifically comparing these to HDT-based approaches. Other trials are examining the role of maintenance therapy post-HDT with these novel drugs with or without steroids. The role of HDT will be further redefined in the coming years with improvements in other therapies.


Asunto(s)
Antineoplásicos/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Factores de Edad , Anciano , Ensayos Clínicos como Asunto/métodos , Humanos , Trasplante Autólogo , Resultado del Tratamiento
16.
Leukemia ; 20(5): 807-13, 2006 May.
Artículo en Inglés | MEDLINE | ID: mdl-16511510

RESUMEN

Chromosomal hyperdiploidy is the defining genetic signature in 40-50% of myeloma (MM) patients. We characterize hyperdiploid-MM (H-MM) in terms of its clinical and prognostic features in a cohort of 220 H-MM patients entered into clinical trials. Hyperdiploid-myeloma is associated with male sex, kappa immunoglobulin subtype, symptomatic bone disease and better survival compared to nonhyperdiploid-MM (median overall survival 48 vs 35 months, log-rank P = 0.023), despite similar response to treatment. Among 108 H-MM cases with FISH studies for common genetic abnormalities, survival is negatively affected by the existence of immunoglobulin heavy chain (IgH) translocations, especially those involving unknown partners, while the presence of chromosome 13 deletion by FISH did not significantly affect survival (median overall survival 50 vs 47 months, log-rank P = 0.47). Hyperdiploid-myeloma is therefore a unique genetic subtype of MM associated with improved outcome with distinct clinical features. The existence of IgH translocations but not chromosome 13 deletion by FISH negatively impacts survival and may allow further risk stratification of this population of MM patients.


Asunto(s)
Deleción Cromosómica , Cromosomas Humanos Par 13/genética , Cromosomas Humanos Par 17/genética , Cadenas Pesadas de Inmunoglobulina/genética , Mieloma Múltiple/genética , Poliploidía , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Aberraciones Cromosómicas , Femenino , Estudios de Seguimiento , Genes p53/genética , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/tratamiento farmacológico , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Estudios Retrospectivos , Tasa de Supervivencia , Translocación Genética , Resultado del Tratamiento
17.
Leukemia ; 31(1): 92-99, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27211265

RESUMEN

Immunoparesis is an adverse prognostic marker in plasma cell proliferative disorders. Its impact in AL amyloidosis has not been explored in depth. Newly diagnosed AL amyloidosis patients (n=998) were evaluated for immunoparesis by two methods. The first method was qualitative, considering the number of suppressed uninvolved immunoglobulins below the lower limit of normal (LLN) (none, partial, all). The second method was quantitative, assessing the average relative difference (ARD) of the uninvolved immunoglobulins from the LLN. Patients with suppression of all the uninvolved immunoglobulins were less likely to achieve very good partial response (VGPR) or better to first-line treatment (44%) compared with patients with partial suppression (68%) or preserved uninvolved immunoglobulins (64%; P<0.0001). In addition, patients with suppression of all the uninvolved immunoglobulins had a shorter survival compared with the respective comparators (median 18 vs 54 vs 52 months; P<0.0001). In the quantitative method, patients with a negative ARD were less likely to achieve VGPR or better (48%) and had a shorter survival (median 24 months) compared with patients with a positive ARD (69%, 57 months, respectively; P<0.0001). In a multivariate analysis for survival, both assessment methods retained an independent impact. Significant immunoparesis has a negative impact on response and survival in newly diagnosed AL amyloidosis.


Asunto(s)
Amiloidosis/inmunología , Tolerancia Inmunológica , Anciano , Amiloidosis/mortalidad , Biomarcadores , Femenino , Humanos , Inmunoglobulinas , Masculino , Persona de Mediana Edad , Pronóstico , Tasa de Supervivencia
18.
Blood Cancer J ; 7(6): e569, 2017 06 16.
Artículo en Inglés | MEDLINE | ID: mdl-28622306

RESUMEN

Little is known about the impact of multiple myeloma (MM) treatment on uninvolved immunoglobulins (Ig). We identified 448 patients who received high-dose dexamethasone (HD-DEX), lenalidomide and dexamethasone (RD), bortezomib and dexamethasone (VD), bortezomib, cyclophosphamide and dexamethasone (VCD) or bortezomib, lenalidomide and dexamethasone (VRD) for newly diagnosed MM at our institution between 2000 and 2013, and who had available data on absolute lymphocyte count (ALC) and quantitative uninvolved Ig at baseline and at the end of four cycles of therapy. Changes in ALC and uninvolved Ig were significantly different across treatments, with VCD and HD-DEX producing reductions in uninvolved Ig, and RD, VD and VRD leading to increases in uninvolved Ig. In addition, treatment with RD, VD and VRD was independently associated with higher odds of achieving a ⩾25% increase in or normalization of the primary uninvolved Ig on multivariate analysis. Although achievement of a humoral response in the primary uninvolved Ig was associated with a higher odds of achieving VGPR or better after four cycles of therapy, it was not associated with improved overall survival. These data highlight the different mechanisms of action of MM drugs and point toward a possible role for the use of VCD in treating antibody-mediated autoimmune disease.


Asunto(s)
Mieloma Múltiple/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Mieloma Múltiple/patología , Inducción de Remisión , Resultado del Tratamiento
19.
Blood Cancer J ; 7(10): e618, 2017 10 20.
Artículo en Inglés | MEDLINE | ID: mdl-29053158

RESUMEN

We studied the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in younger individuals, age 10-49 years, using samples from the National Health and Nutritional Examination Survey (NHANES) III. NHANES prevalence rates were standardized to the 2000 US total population. Among 12 372 individuals (4073 blacks, 4146 Mexican-Americans, 3595 whites, and 558 others), MGUS was identified in 63 persons (0.34%, 95% CI 0.23-0.50). The prevalence of MGUS was significantly higher in blacks (0.88%, 95% CI 0.62-1.26) compared with whites (0.22%, 95% CI 0.11-0.45), P=0.001. The prevalence of MGUS in Mexican-Americans was at an intermediate level (0.41%, 95% CI 0.23-0.73). The disparity in prevalence of MGUS between blacks and whites was most striking in the 40-49 age-group; 3.26% (95% CI 2.04-5.18) versus 0.53% (95% CI 0.20-1.37), P=0.0013. There was a trend to earlier age of onset of MGUS in blacks compared with whites. MGUS was seen in only two persons in the 10-19 age-group (both Mexican-American), and in three persons in the 20-29-year age-group (all of whom were black). In persons less than 50 years of age, MGUS is significantly more prevalent, with up to 10 years earlier age of onset, in blacks compared with whites.


Asunto(s)
Gammopatía Monoclonal de Relevancia Indeterminada/diagnóstico , Mieloma Múltiple/diagnóstico , Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Gammopatía Monoclonal de Relevancia Indeterminada/patología , Mieloma Múltiple/patología , Encuestas Nutricionales , Prevalencia , Factores de Riesgo , Adulto Joven
20.
Leukemia ; 31(1): 130-135, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27457702

RESUMEN

The presence of high numbers of circulating clonal plasma cells (cPCs) in patients with smoldering multiple myeloma (SMM), detected by a slide-based immunofluorescence assay, has been associated with a shorter time to progression (TTP) to MM. The significance of quantifying cPCs via multiparameter flow cytometry, a much more readily available diagnostic modality, in patients with SMM has not been evaluated. This study evaluated 100 patients with a known or new diagnosis of SMM who were seen at the Mayo Clinic, Rochester from January 2008 until December 2013. Patients with ⩾150 cPCs (N=9) were considered to have high number of cPCs based on the 97% specificity and 78% PPV of progression to MM within 2 years of cPC assessment. The median TTP of patients with ⩾150 cPCs was 9 months compared with not reached for patients with <150 cPCs (P<0.001). Thus, quantification of cPCs via multiparametric flow cytometry identifies patients with SMM at very high risk of progression to MM within 2 years and warrants confirmation in larger studies. In the future, this may allow reclassification of such patients as having MM requiring therapy prior to them enduring end-organ damage.


Asunto(s)
Mieloma Múltiple/diagnóstico , Células Neoplásicas Circulantes/patología , Células Plasmáticas/patología , Adulto , Anciano , Anciano de 80 o más Años , Recuento de Células , Células Clonales/patología , Progresión de la Enfermedad , Diagnóstico Precoz , Femenino , Citometría de Flujo/métodos , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/patología
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