RESUMEN
BACKGROUND: Erdheim-Chester disease (ECD) is a rare condition and there is limited information available regarding its cutaneous manifestations. OBJECTIVES: To describe the clinical and histopathological features of cutaneous involvement in ECD. METHODS: This study is a single-centre retrospective analysis of patients 18 years old and older with biopsy-proven diagnosis of ECD between 1 January 1990 and 1 April 2017. Patients from this cohort were screened for cutaneous manifestations, and BRAF c.1799T>A (p.V600E) mutational analysis was conducted in novel skin manifestations. Primary outcomes included cutaneous manifestations (morphology and topography of lesions) and BRAF mutation status in novel cutaneous findings. RESULTS: Of 71 patients with ECD, 15 patients (21%; median age 52 years) presented with cutaneous manifestations. The most common finding was the presence of xanthelasma-like lesions (n = 8). Two patients had nonfacial cutaneous xanthomas. Seven patients presented with nonxanthomatous cutaneous involvement, with the most common finding being subcutaneous nodules (n = 5). A single patient presented with granuloma annulare-like lesions. Another patient with mixed ECD and Langerhans cell histiocytosis presented with lightly scaling, pink-red macules. In three patients, the appearance of skin lesions was the first manifestation of the disease. Most patients presented with bone/extremity pain, weight loss and other constitutional symptoms at the time of diagnosis. The BRAF V600E mutation was not found in patients with panniculitis-like and granuloma annulare-like lesions. CONCLUSIONS: The most common presentation in ECD is the presence of periorbital xanthelasma-like lesions. Other presentations include nonfacial cutaneous xanthomas, panniculitis-like lesions and granuloma annulare-like lesions. Associated symptoms at presentation include bone/extremity pain and weight loss. What's already known about this topic? Erdheim-Chester disease is a rare form of non-Langerhans cell histiocytosis characterized by lipid-laden macrophage infiltration of tissue and subsequent fibrosis. Cutaneous involvement is found in approximately 25% of patients, with the majority presenting with periorbital xanthelasma-like lesions. What does this study add? We report two novel cutaneous findings: panniculitis-like lesions and granuloma annulare-like lesions. Associated bone/extremity pain and weight loss should raise suspicion for Erdheim-Chester disease.
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Enfermedad de Erdheim-Chester , Histiocitosis de Células de Langerhans , Enfermedades de la Piel , Adolescente , Enfermedad de Erdheim-Chester/diagnóstico por imagen , Enfermedad de Erdheim-Chester/genética , Humanos , Persona de Mediana Edad , Mutación , Estudios Retrospectivos , Enfermedades de la Piel/genéticaRESUMEN
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.
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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/sangreRESUMEN
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.
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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 TratamientoRESUMEN
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.
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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 JovenRESUMEN
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.
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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 TratamientoRESUMEN
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.
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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 TratamientoRESUMEN
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.
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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/patologíaRESUMEN
Fluorescence in situ hybridization evaluation is essential for initial risk stratification in multiple myeloma. While the presence of specific cytogenetic high-risk abnormalities (HRA) is known to confer a poor prognosis, less is known about the cumulative effect of multiple HRA. We studied 1181 patients with newly diagnosed multiple myeloma who received novel agents as first-line therapy. High-risk abnormalities were defined as t(4;14), t(14;16), t(14;20) and del(17p). There were 884 patients (75%) without any HRA and 297 patients (25%) with HRA, including 262 (22%) with one HRA and 35 (3%) with two HRA. The presence of one HRA (versus zero, hazard ratio (HR) 1.65, 95% confidence interval (CI) 1.32-2.05, p<0.001) and the presence of two HRA (versus zero, HR 3.15, 95% CI 2.00-4.96, p<0.001) were of prognostic significance after adjusting for other prognostic factors. Abnormalities of chromosome 13 were of prognostic significance independent of the established HRA: Monosomy 13 (HR 1.27, 95% CI 1.04-1.56, P=0.022) and del(13q) (HR 0.48, 95% CI 0.28-0.81, P=0.006) with opposite effects. Patients with HRA experienced worse overall survival suggesting a cumulative adverse effect of multiple HRA. Abnormalities of chromosome 13 were of prognostic significance after adjusting for other prognostic factors.
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Cromosomas Humanos Par 13/genética , Mieloma Múltiple/genética , Mieloma Múltiple/mortalidad , Translocación Genética , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/terapia , Estudios Retrospectivos , Factores de RiesgoRESUMEN
We analyzed the utility of Revised International staging system (RISS) in an unselected cohort of newly diagnosed multiple myeloma (NDMM; cohort 1), and relapsed/refractory multiple myeloma (RRMM; cohort 2) patients. Cohort 1 included 1900 patients seen within 90 days of diagnosis, from 2005 to 2015, while cohort 2 had 887 patients enrolled in 23 clinical trials at Mayo Clinic. The overall survival (OS) and progression-free survival (PFS) was calculated from the time since diagnosis or trial registration. The median estimated follow up was 5 and 2.3 years for Cohorts 1 and 2, respectively. Among 1067 patients evaluable in Cohort 1, the median OS and PFS was 10 and 2.8 years for RISS stage I, 6 and 2.7 years for RISS stage II and 2.6 and 1.3 years for RISS stage III (P<0.0001). Among 456 patients evaluable in Cohort 2, the median OS and PFS was 4.3 and 1.1 years for RISS stage I, 2 and 0.5 years for RISS stage II and 0.8 and 0.2 years for RISS stage III (P<0.0001). In conclusions, RISS gives a better differentiation of NDMM as well as RRMM patients into three survival subgroups and should be used to stratify patients in future clinical trials.
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Mieloma Múltiple/diagnóstico , Estadificación de Neoplasias/métodos , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Mieloma Múltiple/patología , Pronóstico , Adulto JovenRESUMEN
The significance of interphase fluorescence in situ hybridization (iFISH) by regimen type was assessed in 692 immunoglobulin light-chain (AL) amyloidosis patients with iFISH at diagnosis. First-line treatment was categorized as stem cell transplant and three non-transplant regimens. The most common abnormality was t(11;14) (49% of patients) followed by monosomy 13/del(13q) (36%) and trisomies (26%). A lower rate of very good partial response (VGPR) or better was observed in patients with t(11;14) treated with bortezomib-based (52% vs 77%; P=0.004) and IMiD-based regimens (13% vs 54%; P=0.04) compared with those lacking t(11;14). This corresponded to an inferior overall survival (OS) in t(11;14)-positive bortezomib-treated (median 15 vs 27 months; P=0.05) and IMiD-treated patients (median 12 vs 32 months; P=0.05). The inferior OS associated with t(11;14) bortezomib-treated patients was restricted to patients with favorable disease. Trisomies were associated with a shorter OS (median 29 vs 69 months; P=0.001), reaching statistical significance only for melphalan (median 15 vs 32 months; P=0.02). Multivariate analysis confirmed an independent survival impact for trisomies in the entire cohort and for t(11;14) among bortezomib-treated patients. iFISH is prognostic in untreated AL amyloidosis and may influence treatment selection. Patients with t(11;14) should be considered for ASCT or standard-dose melphalan at diagnosis because the survival disadvantage may be abrogated.
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Amiloidosis/genética , Cromosomas Humanos Par 11 , Cromosomas Humanos Par 14 , Hibridación Fluorescente in Situ/métodos , Interfase , Translocación Genética , Anciano , Amiloidosis/mortalidad , Amiloidosis/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , TrisomíaRESUMEN
Large granular lymphocyte (LGL) leukemia is a lymphoproliferative disorder of cytotoxic cells. T-cell LGL (T-LGL) leukemia is characterized by accumulation of cytotoxic T cells in blood and infiltration of the bone marrow, liver or spleen. Population-based studies have not been reported in LGL leukemia. We present clinical characteristics, natural history and risk factors for poor survival in patients with LGL leukemia using the Surveillance, Epidemiology, and End Results Program (SEER) and the United States National Cancer Data Base (NCDB). LGL leukemia is an extremely rare disease with the incidence of 0.2 cases per 1 000 000 individuals. The median age at diagnosis was 66.5 years with females likely to be diagnosed at 3 years earlier compared with males. Analysis of patient-level data using NCDB (n=978) showed that 45% patients with T-LGL leukemia required some form of systemic treatment at the time of diagnosis. T-LGL leukemia patients have reduced survival compared with general population, with a median overall survival of 9 years. Multivariate analysis showed that age >60 years at the time of diagnosis and the presence of significant comorbidities were independent predictors of poor survival.
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Leucemia Linfocítica Granular Grande/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Incidencia , Leucemia Linfocítica Granular Grande/diagnóstico , Leucemia Linfocítica Granular Grande/mortalidad , Leucemia Linfocítica Granular Grande/terapia , Masculino , Persona de Mediana Edad , Vigilancia de la Población , Programa de VERF , Análisis de Supervivencia , Estados UnidosRESUMEN
Outcomes for patients with multiple myeloma (MM) have improved in recent years owing to use of novel agents and high-dose therapy followed by autologous stem cell transplant (ASCT). We analyzed the outcomes of 511 consecutive patients treated with novel therapies at our institution between 2006 and 2014 to determine the impact of relapse within 12 months of initiating treatment. A total of 82 patients (16.0%) experienced early relapse, with median time to relapse of 8.0 months (95% confidence interval (CI); 6.3, 8.9). Median overall survival (OS) was significantly worse for this group at 21.0 months (95% CI; 16.3, 27.2) vs not reached (NR) (95% CI; 96.3, NR) for those with late relapse (P<0.001). Survival outcomes remained poor among early relapse patients irrespective of depth of response to initial therapy. In multivariate analysis, low albumin and high-risk cytogenetics predicted early relapse. Outcomes of early relapse from early ASCT were also considered; median OS from ASCT for those relapsing within 12 months was 23.1 months (95% CI; 15.7, 32.4) vs 122.2 months (95% CI; 111.5, 122.2) for the remaining patients (P<0.001). Early relapse remains a marker of poor prognosis in the current era, and such patients should be targeted for clinical trials.
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Mieloma Múltiple/diagnóstico , Mieloma Múltiple/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Citogenética , Femenino , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Mieloma Múltiple/terapia , Pronóstico , Recurrencia , Albúmina Sérica , Tasa de Supervivencia , Factores de Tiempo , Trasplante Autólogo , Resultado del TratamientoRESUMEN
Early high-dose therapy (HDT), consisting of high-dose melphalan and autologous stem cell transplantation following doublet or triplet novel agent induction, is a preferred management strategy for transplant-eligible myeloma patients. We set out to examine the utility of the current fluorescence in situ hybridization (FISH)-based risk stratification in a homogenously treated population of transplant-eligible myeloma patients receiving novel induction regimens and early HDT with or without posttransplant maintenance therapy. FISH was available in 409 patients at the time of diagnosis for patients receiving HDT within 12 months of diagnosis. We present comprehensive outcomes for chromosome 14 translocations and 17p abnormalities that both support and refute current risk stratification models. In contrast to its current classification as a marker of 'standard risk' (SR), t(11;14) was associated with inferior overall survival (OS) when compared with the classical SR cohort. The use of novel agent maintenance therapy (bortezomib or lenalidomide) following early HDT ameliorates the negative prognostic value of high-risk (HR) cytogenetic markers. HR patients who received maintenance following early HDT had similar OS compared with the SR cohort at 5 years.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/terapia , Adulto , Anciano , Bortezomib/uso terapéutico , Cromosomas Humanos Par 11 , Cromosomas Humanos Par 14 , Cromosomas Humanos Par 17 , Análisis Citogenético , Dexametasona/uso terapéutico , Humanos , Hibridación Fluorescente in Situ , Quimioterapia de Inducción/métodos , Lenalidomida , Masculino , Melfalán/uso terapéutico , Persona de Mediana Edad , Mieloma Múltiple/genética , Mieloma Múltiple/mortalidad , Pronóstico , Inducción de Remisión , Estudios Retrospectivos , Análisis de Supervivencia , Talidomida/análogos & derivados , Talidomida/uso terapéutico , Translocación Genética , Trasplante Autólogo , Resultado del TratamientoRESUMEN
Although clinical improvement is almost universal with therapy in patients with POEMS (an acronym for polyneuropathy, organomegaly, endocrinopathies, monoclonal protein and a variety of skin changes) syndrome, outcomes and management of patients who relapse or progress (R/P) after first-line treatment have not been described. We retrospectively identified 262 patients with POEMS syndrome treated at the Mayo Clinic from 1974 to 2014 and who had follow-up information. The 5-year progression-free survival (PFS) and overall survival (OS) was 58% and 78%, respectively. Median time to R/P was 42 months. Seventy-nine patients (30%) had an R/P, with 52 (19%) experiencing a symptomatic R/P. Eighteen patients relapsed with symptoms or signs that were not documented at diagnosis. Median times to vascular endothelial growth factor, hematologic, radiographic and clinical R/P were 35 months (range, 4-327 months), 72 months (range, 4-327 months), 51 months (range, 4-327 months) and 48 months (range, 6-311 months), respectively. On multivariate analyses, low albumin at diagnosis and failure to achieve a complete hematologic response to first-line therapy were independent risk factors for PFS. Thirty patients had documentation of a second R/P at a median of 26 months from diagnosis of the first R/P. An early R/P was a risk factor for death, but most patients with an R/P had salvageable disease. A majority of patients are still without R/P at 5 years from diagnosis.
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Progresión de la Enfermedad , Síndrome POEMS/diagnóstico , Síndrome POEMS/terapia , Adulto , Anciano , Anciano de 80 o más Años , Terapia Combinada , Manejo de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Síndrome POEMS/mortalidad , Síndrome POEMS/patología , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Terapia Recuperativa/métodos , Tasa de Supervivencia , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular/sangre , Adulto JovenRESUMEN
Cytogenetic evaluation at the time of diagnosis is essential for risk stratification in multiple myeloma, however little is known about the occurrence and prognostic significance of cytogenetic evolution during follow-up. We studied 989 patients with multiple myeloma, including 304 patients with at least two cytogenetic evaluations. Multivariable-adjusted regression models were used to assess the associations between the parameters of interest and cytogenetic evolution as well as overall survival. The prognostic significance of baseline cytogenetic abnormalities was most pronounced at the time of diagnosis and attenuated over time. In the patients with serial cytogenetic evaluations, the presence of t(11;14) at the time of diagnosis was associated with decreased odds of cytogenetic evolution during follow-up (odds ratio (OR)=0.22, 95% confidence interval (CI)=0.09-0.56, P=0.001), while the presence of at least one trisomy or tetrasomy was associated with increased odds (OR=2.96, 95% CI=1.37-6.42, P=0.006). The development of additional abnormalities during the 3 years following diagnosis was associated with increased subsequent mortality (hazard ratio=3.31, 95% CI=1.73-6.30, P<0.001). These findings emphasize the importance of the underlying clonal disease process for risk assessment and suggest that selected patients may benefit from repeated risk stratification.
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Transformación Celular Neoplásica/genética , Aberraciones Cromosómicas , Evolución Clonal/genética , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/genética , Adulto , Anciano , Anciano de 80 o más Años , Médula Ósea/metabolismo , Médula Ósea/patología , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Cariotipo , Masculino , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Poliploidía , Pronóstico , Modelos de Riesgos Proporcionales , Adulto JovenRESUMEN
PURPOSE: To review the pharmacodynamics, pharmacokinetics, toxicities, and relative clinical activities of cisplatin and carboplatin. Through a search of the MEDLINE database, we identified phase III clinical trials and pharmacologic studies comparing cisplatin and carboplatin published in the English language medical literature from January 1966 to December 1997. RESULTS: Prospective randomized trials comparing cisplatin to carboplatin were identified for ovarian (n = 12), germ cell (n = 4), non-small-cell lung (n = 1), small-cell lung (n = 3), and head and neck (n = 4) cancers. Carboplatin and cisplatin were equally effective in suboptimally debulked ovarian cancer and extensive-stage small-cell lung cancer. One study each showed a trend toward better survival in favor of cisplatin for patients with optimally debulked ovarian and limited-stage small-cell lung cancers. These results were, however, based on subset analyses. In germ cell tumors, carboplatin was inferior because of lower relapse-free survival rates. Cisplatin produced superior response rates and survival in head and neck cancers. There are no published randomized phase III studies of bladder, cervical, endometrial, and esophageal cancers. CONCLUSION: Carboplatin does not possess equivalent activity to cisplatin in all platinum-sensitive tumors. Carboplatin can replace cisplatin in chemotherapy regimens for suboptimally debulked ovarian cancer. Two ongoing studies will address the same question in optimally debulked disease. Carboplatin can also be substituted for cisplatin in the treatment of non-small-cell and extensive-stage small-cell lung cancers. Its role in limited-stage small-cell lung cancer needs to be investigated further. Carboplatin is inferior to cisplatin in germ cell, head and neck, and esophageal cancers. Randomized studies are needed to determine whether carboplatin has equivalent efficacy to cisplatin in bladder, cervical, and endometrial cancers.
Asunto(s)
Antineoplásicos/uso terapéutico , Carboplatino/uso terapéutico , Cisplatino/uso terapéutico , Antineoplásicos/efectos adversos , Antineoplásicos/farmacocinética , Carboplatino/efectos adversos , Carboplatino/farmacocinética , Cisplatino/efectos adversos , Cisplatino/farmacocinética , Femenino , Germinoma/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológicoRESUMEN
Renal impairment (RI) is seen in over a quarter of patients with newly diagnosed multiple myeloma (NDMM). It is not clear if reversal of RI improves the outcome to that expected for NDMM patients without RI. We evaluated 1135 consecutive patients with NDMM seen at the Mayo Clinic between January 2003 and December 2012. RI was defined as having a creatinine clearance (CrCl) <40ml/min. The median overall survival (OS) for patients with RI at diagnosis receiving and not receiving novel agent induction therapy was not reached vs 46 months (P<0.001). The median OS for patients with CrCl ⩾40 ml/min at diagnosis, CrCl <40 ml/min at diagnosis but improved to ⩾40 ml/min and CrCl <40 ml/min at diagnosis and remained <40 ml/min, were 112, 56 and 33 months, respectively (P<0.001). The complete renal response rate for patients with RI at diagnosis receiving novel agent induction therapy compared to the rest was 40 vs 16% (P<0.001). In conclusion, patients with reversal of RI have improved outcomes, but it remains inferior to patients with normal renal function at diagnosis. These results have implications for identifying early treatment strategies for patients at risk of developing renal insufficiency.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Mieloma Múltiple/tratamiento farmacológico , Terapia Neoadyuvante , Insuficiencia Renal/tratamiento farmacológico , Insuficiencia Renal/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Citogenética , Femenino , Tasa de Filtración Glomerular , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Mieloma Múltiple/sangre , Mieloma Múltiple/complicaciones , Mieloma Múltiple/patología , Estadificación de Neoplasias , Insuficiencia Renal/sangre , Insuficiencia Renal/complicaciones , Insuficiencia Renal/patología , Resultado del TratamientoRESUMEN
Importance of interphase fluorescent in situ hybridization (FISH) with cytoplasmic staining of immunoglobulin FISH (cIg-FISH) on bone marrow is not well understood in light chain amyloidosis (AL). This is in contrast with multiple myeloma where prognostic and treatment related decisions are dependent on cytogenetic testing. This retrospective study reviewed 401 AL patients with cIg-FISH testing performed at our institution between 2004 and 2012. Eighty-one percent of patients had an abnormal cIg-FISH. Common abnormalities involved translocations of chromosome 14q32 (52%), specifically: t(11;14) (43%), t(14;16) (3%) and t(4;14) (2%). Other common abnormalities include monosomy 13/deletion 13q (30%), trisomies 9 (20%), 15 (14%), 11 (10%) and 3 (10%). Median overall survival for this cohort of patients is 3.5 years. When plasma cell burden was greater than 10% trisomies predicted for worse survival (44 vs 19 months), and when it was ⩽10% t(11;14) predicted for worse survival (53 months vs not reached). Abnormal cIg-FISH was significantly associated with advanced cardiac involvement, and remained a prognostic factor on multivariate analysis. This large AL cohort demonstrates that abnormal FISH at diagnosis is prognostic for survival and advanced cardiac disease. Particularly, trisomies and t(11;14) affect survival when degree of plasma cell burden is considered.
Asunto(s)
Amiloidosis/genética , Amiloidosis/patología , Hibridación Fluorescente in Situ , Adulto , Anciano , Anciano de 80 o más Años , Amiloidosis/mortalidad , Aberraciones Cromosómicas , Femenino , Cardiopatías/etiología , Humanos , Cadenas Ligeras de Inmunoglobulina , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de RiesgoRESUMEN
To define the natural history of asymptomatic meningioma found incidentally on a neuroimaging study, we performed a retrospective analysis of 35 such patients. There were 32 women and three men, with a mean age of 67 years and a mean follow-up of 74 months. Four tumors had progressed on subsequent imaging, and one patient developed symptoms related to the meningioma. Noncalcified tumors were more likely to progress than calcified tumors.
Asunto(s)
Meningioma/mortalidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Calcinosis/diagnóstico por imagen , Calcinosis/mortalidad , Niño , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Meningioma/diagnóstico por imagen , Persona de Mediana Edad , Minnesota/epidemiología , Estudios Retrospectivos , Tomografía Computarizada por Rayos XRESUMEN
Thrombosis resulting from intravenous immunoglobulin infusion is a relatively unknown complication. We describe a patient who developed deep venous thrombosis of her left arm shortly after intravenous immunoglobulin administration. In addition, we review the thrombotic incidences reported in the literature and the possible association with hepatic veno-occlusive disease after bone marrow transplantation. Measures that can potentially prevent this complication are discussed.