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1.
Am J Hematol ; 94(6): 635-640, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30859608

RESUMO

The risk of venous thromboembolism (VTE) is higher in myeloma patients receiving immunomodulatory compounds. A VTE prophylaxis using low-molecular-weight heparin or aspirin is therefore proposed. Apixaban is an oral direct anti-Xa. Several studies have shown the efficacy and safety of apixaban in VTE prophylaxis compared to enoxaparin. The objective of this prospective phase 2 pilot study was to assess the risk of VTE and bleeding in patients with myeloma treated with immunomodulatory compounds lenalidomide (len) or thalidomide (thal), using apixaban in a preventive scheme. Myeloma patients requiring Melphalan-Prednisone-Thalidomide in the first line, or Lenalidomide-Dexamethasone in the relapse setting received apixaban, 2.5 mg x 2/day for 6 months. Venous (pulmonary embolism-PE, or symptomatic proximal or distal deep vein thrombosis-DVT, or all proximal asymptomatic events detected by systematic proximal bilateral compression ultrasound) or arterial thrombotic events, and bleeding events (ISTH 2005) were registered. One hundred and four patients were enrolled (mean age 69.8 ± 7.8 years), 11 in first line and 93 in relapse. Two venous thrombotic events were observed, for example, an asymptomatic proximal DVT and a symptomatic distal DVT, in the context of apixaban stopped 14 days before, due to lenalidomide-induced thrombocytopenia. No PE or arterial cardiovascular events were reported. Only one major and 11 CRNM hemorrhages were reported. These data must now be confirmed on a randomized large study.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Mieloma Múltiplo/tratamento farmacológico , Pirazóis/administração & dosagem , Piridonas/administração & dosagem , Tromboembolia Venosa/prevenção & controle , Idoso , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Feminino , Humanos , Lenalidomida/administração & dosagem , Lenalidomida/efeitos adversos , Masculino , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos , Talidomida/administração & dosagem , Talidomida/efeitos adversos , Tromboembolia Venosa/induzido quimicamente
2.
Blood ; 128(25): 2941-2948, 2016 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-27729323

RESUMO

Guidelines for monitoring multiple myeloma (MM) patients expressing light chains only (light-chain MM [LCMM]) rely on measurements of monoclonal protein in urine. Alternatively, serum free light chain (sFLC) measurements have better sensitivity over urine methods, however, demonstration that improved sensitivity provides any clinical benefit is lacking. Here, we compared performance of serum and urine measurements in 113 (72κ, 41λ) newly diagnosed LCMM patients enrolled in the Intergroupe Francophone du Myélome (IFM) 2009 trial. All diagnostic samples (100%) had an abnormal κ:λ sFLC ratio, and involved (monoclonal) FLC (iFLC) expressed at levels deemed measurable for monitoring (≥100 mg/L). By contrast, only 64% patients had measurable levels of monoclonal protein (≥200 mg per 24 hours) in urine protein electrophoresis (UPEP). After 1 and 3 treatment cycles, iFLC remained elevated in 71% and 46% of patients, respectively, whereas UPEP reported a positive result in 37% and 18%; all of the patients with positive UPEP at cycle 3 also had elevated iFLC levels. Importantly, elevated iFLC or an abnormal κ:λ sFLC ratio after 3 treatment cycles associated with poorer progression-free survival (P = .006 and P < .0001, respectively), whereas positive UPEP or urine immunofixation electrophoresis (uIFE) did not. In addition, patients with an abnormal κ:λ sFLC ratio had poorer overall survival (P = .022). Finally, early normalization of κ:λ sFLC ratio but not negative uIFE predicted achieving negative minimal residual disease, as determined by flow cytometry, after consolidation therapy (100% positive predictive value). We conclude that improved sensitivity and prognostic value of serum over urine measurements provide a strong basis for recommending the former for monitoring LCMM patients.


Assuntos
Cadeias Leves de Imunoglobulina/sangue , Cadeias Leves de Imunoglobulina/urina , Mieloma Múltiplo/sangue , Mieloma Múltiplo/urina , Adulto , Quimioterapia de Consolidação , Humanos , Quimioterapia de Indução , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Padrões de Referência , Análise de Sobrevida
3.
Blood ; 125(9): 1411-7, 2015 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-25575538

RESUMO

The combination of pomalidomide and low-dose dexamethasone (Pom-Dex) can be safely administered to patients with end-stage relapsed/refractory multiple myeloma (RRMM). However, we observed a shorter median progression-free survival (PFS) and overall survival (OS) in these patients when characterized with adverse cytogenetics (deletion 17p and translocation [4;14]) in the Intergroupe Francophone Myélome (IFM) 2009-02 trial. We then sought to determine whether MM with adverse cytogenetics would benefit more from Pom-Dex if exposed earlier in the multicenter IFM 2010-02 trial. The intention-to-treat population included 50 patients, with a median age of 63 years (38% were ≥65 years). Interestingly, there was a striking difference in time to progression (TTP), duration of response, and overall response rate (ORR) according to the presence of del(17p) compared with t(4;14) (TTP, 7.3 vs 2.8 months; duration of response, 8.3 vs 2.4 months; and ORR, 32% vs 15%). OS was prolonged after Pom-Dex, particularly in t(4;14), given the short TTP, suggesting that patients were rescued at relapse with further lines of therapy. Pom-Dex, a doublet immunomodulatory drug-based regimen, is active and well tolerated in adverse cytogenetic patients with early RRMM, particularly in those with del(17p), who are characterized by a high and rapid development of a refractoriness state and known for their poor prognosis. Future studies will determine the underlying mechanisms of Pom-Dex activity in del(17p). This trial is registered at www.clinicaltrials.gov as #NCT01745640.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 17/genética , Cromossomos Humanos Par 4/genética , Deleção de Genes , Mieloma Múltiplo/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Translocação Genética/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Dexametasona/administração & dosagem , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/genética , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/patologia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida , Talidomida/administração & dosagem , Talidomida/análogos & derivados
5.
Blood ; 118(14): 3777-84, 2011 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-21757618

RESUMO

Xanthomas are a common manifestation of lipid metabolism disorders. They include hyperlipemic xanthoma, normolipemic xanthoma, and a related condition, necrobiotic xanthogranuloma (NXG). All 3 forms can be associated with monoclonal immunoglobulin (MIg). In an attempt to improve diagnosis, understanding, and treatment of this association, we retrospectively analyzed a personal series of 24 patients (2 hyperlipemic xanthoma, 11 normolipemic xanthoma, and 11 NXG) and 230 well-documented reports from the literature. With the exception of the nodules and plaques featured in NXG, the clinical presentation of xanthomatous lesions usually resembled that seen in common hyperlipidemic forms and could not be used to suspect MIg-associated xanthomas. Extracutaneous sites were not rare. The MIg was an IgG in 80% of cases. Myeloma was diagnosed in 35%. Hypocomplementemia with low C4 fraction was present in 80% of studied patients. Low C1 inhibitor serum levels were found in 53%. Cryoglobulinemia was detected in 27%. These abnormalities suggest immune complex formation because of interactions between the MIg and lipoproteins and argue in favor of a causal link between MIg and xanthomas. Monoclonal gammopathy therapy could thus be an option. Indeed, among the patients who received chemotherapy, hematologic remission was accompanied by improvement in xanthoma lesions in several cases.


Assuntos
Paraproteinemias/complicações , Paraproteinemias/terapia , Xantomatose/complicações , Xantomatose/terapia , Humanos , Paraproteinemias/diagnóstico , Paraproteinemias/patologia , Estudos Retrospectivos , Pele/patologia , Xantomatose/diagnóstico , Xantomatose/patologia
6.
Blood ; 117(6): 2009-11, 2011 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-20962323

RESUMO

Many trials in myeloma are stratified on cytogenetic abnormalities. Among them, the most commonly chosen are the t(4;14), the del(17p), and the t(14;16). If data are well established for t(4;14) and del(17p), very few data support the use of t(14;16). To address this issue, we retrospectively analyzed 1003 patients with newly diagnosed myeloma for this abnormality. We identified 32 patients with the t(14;16). Compared with patients lacking the t(14;16), we did not observe any difference in overall survival (P = .28). Moreover, in multivariate analyses, the t(14;16) was not prognostic (P = .39). In conclusion, our data do not support the use of t(14;16)-specific probes in the diagnostic panels of multiple myeloma.


Assuntos
Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 16/genética , Mieloma Múltiplo/genética , Translocação Genética , Idoso , Humanos , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Análise Multivariada , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida
7.
Blood ; 117(11): 3041-4, 2011 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-21098740

RESUMO

In the 2005-01 trial, we have demonstrated that bortezomib-dexamethasone as induction therapy before autologous stem cell transplantation was superior to vincristine-adriamycin-dexamethasone. We conducted a post-hoc analysis to assess the prognostic impact of initial characteristics as well as response to therapy in patients enrolled in this study. Multivariate analysis showed that ISS stages 2 and 3 and achievement of response less than very good partial response (VGPR) both after induction therapy and after autologous stem cell transplantation were adverse prognostic factors for progression-free survival, the most important one being achievement of response less than VGPR after induction. Progression-free survival was significantly improved with bortezomib-dexamethasone induction therapy in patients with poor-risk cytogenetics and ISS stages 2 and 3 compared with vincristine-adriamycin-dexamethasone. In these 2 groups of patients, achievement of at least VGPR after induction was of major importance. This study is registered with EudraCT (https://eudract.ema.europa.eu; EUDRACT 2005-000537-38) and http://clinicaltrials.gov (NCT00200681).


Assuntos
Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Adulto , Intervalo Livre de Doença , Humanos , Análise de Intenção de Tratamento , Pessoa de Meia-Idade , Prognóstico , Indução de Remissão , Fatores de Tempo , Resultado do Tratamento
8.
Blood ; 118(22): 5752-8; quiz 5982, 2011 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-21849487

RESUMO

The Intergroupe Francophone du Myelome conducted a randomized trial to compare bortezomib-dexamethasone (VD) as induction before high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) to a combination consisting of reduced doses of bortezomib and thalidomide plus dexamethasone (vtD) in patients with multiple myeloma. Overall, a total of 199 patients were centrally randomly assigned to receive VD or vtD. After 4 cycles, the complete response (CR) rate was the same in both groups (13% in the vtD arm, 12% in the VD arm, P = .74). However, the CR plus very good partial response (VGPR) rate was significantly higher in the vtD arm (49% vs 36%, P = .05). After ASCT, the CR plus VGPR rate was significantly higher in the vtD arm (74% vs 58%, P = .02). The reduced doses of bortezomib and thalidomide translated into a reduced incidence of peripheral neuropathy (PN): grade ≥ 2 PN were reported in 34% in the VD arm versus 14% in the vtD arm (P = .001). vtD, including reduced doses of bortezomib and thalidomide, yields higher VGPR rates compared with VD and can be considered a new effective triplet combination before HDT/ASCT.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ácidos Borônicos/administração & dosagem , Dexametasona/administração & dosagem , Quimioterapia de Indução , Mieloma Múltiplo/terapia , Pirazinas/administração & dosagem , Transplante de Células-Tronco , Talidomida/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ácidos Borônicos/efeitos adversos , Bortezomib , Terapia Combinada , Dexametasona/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Humanos , Quimioterapia de Indução/métodos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/mortalidade , Pirazinas/efeitos adversos , Transplante de Células-Tronco/métodos , Análise de Sobrevida , Talidomida/efeitos adversos , Fatores de Tempo , Transplante Autólogo , Resultado do Tratamento
9.
Blood ; 117(10): 2778-82, 2011 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-21239701

RESUMO

Erdheim-Chester disease (ECD) is a rare form of non-Langerhans histiocytosis, with noncodified therapeutic management and high mortality. No treatment has yet been shown to improve survival in these patients. We conducted a multicenter prospective observational cohort study to assess whether extraskeletal manifestations and interferon-α treatment would influence survival in a large cohort of ECD patients. To achieve this goal, we thoroughly analyzed the clinical presentation of 53 patients with biopsy-proven ECD, and we performed a survival analysis using Cox proportional hazard model. Fifty-three patients (39 men and 14 women) with biopsy-proven ECD were followed up between November 1981 and November 2010. Forty-six patients (87%) received interferon-α and/or PEGylated interferon-α. Multivariate survival analysis using Cox proportional hazard model revealed that central nervous system involvement was an independent predictor of death (hazard ratio = 2.51; 95% confidence interval, 1.28-5.52; P = .006) in our cohort. Conversely, treatment with interferon-α was identified as an independent predictor of survival (hazard ratio = 0.32; 95% confidence interval, 0.14-0.70; P = .006). Although definitive confirmation would require a randomized controlled trial, these results suggest that interferon-α improves survival in ECD patients. This may be seen as a significant advance, as it is the first time a treatment is shown to improve survival in this multisystemic disease with high mortality.


Assuntos
Encéfalo/patologia , Doença de Erdheim-Chester/tratamento farmacológico , Doença de Erdheim-Chester/mortalidade , Doença de Erdheim-Chester/patologia , Fatores Imunológicos/uso terapêutico , Interferon-alfa/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Estudos de Coortes , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Adulto Jovem
10.
Clin Rheumatol ; 39(9): 2707-2713, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32206974

RESUMO

OBJECTIVE: Takayasu arteritis (TAK) is a large vessel vasculitis affecting young women of childbearing age. The outcome of pregnancies in TAK patients, factors associated with maternal and foetal complications and adverse outcomes were analysed. METHODS: All pregnancies in women with a TAK diagnosis were retrospectively included from 20 French hospitals providing care for TAK, until August 2015. RESULTS: The study consisted of 43 pregnancies in 33 women, including 29 with a pre-existing TAK diagnosis and 4 diagnosed during pregnancy. Complications were observed in 20 pregnancies (47%), including 35% with arterial hypertension (n = 15), 9% with pre-eclampsia (n = 4), 2% with HELLP syndrome (n = 1) and 14% with intrauterine growth restriction (IUGR, n = 6, leading in one case to a medically indicated termination of pregnancy). There were 42 live births (98%) at a median term of 38 [27-42] weeks gestation including 9 before 37 weeks (21%). The median birth weight was 2940 [610-4310] grams. Five children (12%) required transfer to a neonatal intensive care unit. One premature boy (27 weeks gestation) died after 2 days. Treatment during pregnancy included steroids (n = 25/43; 58%), azathioprine (n = 9/43; 21%) and infliximab (n = 1/43; 2%). The risk of developing arterial hypertension during pregnancy was associated with previous chronic arterial hypertension and with an infra-diaphragmatic vasculitis injury (P = 0.01 and P = 0.04, respectively). No correlation was reported between TAK activity and any of the obstetrical complications described in the study. CONCLUSION: This study showed a high rate of adverse obstetrical complications without significant impact on live birth rates. Pregnancy did not appear to influence TAK disease activity. Key Points • We observed a high rate of adverse obstetrical complications in women with Takayasu arteritis; however, the rate of live births was high. Pregnancy did not appear to influence TA disease activity.


Assuntos
Complicações Cardiovasculares na Gravidez , Arterite de Takayasu , Criança , Feminino , Humanos , Recém-Nascido , Gravidez , Complicações Cardiovasculares na Gravidez/epidemiologia , Resultado da Gravidez , Estudos Retrospectivos , Fatores de Risco , Arterite de Takayasu/complicações , Arterite de Takayasu/epidemiologia
11.
J Rheumatol ; 45(1): 95-102, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29093153

RESUMO

OBJECTIVE: Exercise limitation in patients with systemic sclerosis (SSc) is often multifactorial and related to complications such as interstitial lung disease (ILD), pulmonary vasculopathy (PV), left ventricular dysfunction (LVD), and/or peripheral/muscular limitation (PML). We hypothesized that cardiopulmonary exercise testing (CPET) could not only suggest and rank competing etiologies, but also highlight peripheral impairment. METHODS: Clinical, resting pulmonary function testing, and CPET data from patients with SSc referred for exercise limitation between October 2009 and November 2015 were retrospectively analyzed in this bi-center study. Patients were categorized as having ILD, PV, LVD, and/or PML based on CPET response patterns and the diagnoses were matched with results from the reference investigations. The latter consisted of transthoracic echocardiography, chest computed tomography scan, and right heart catheterization (RHC). RESULTS: Twenty-seven patients presented with CPET profiles consistent with ILD (n = 16), PV (n = 15), LVD (n = 5), and PML (n = 19). None of the subjects had a normal CPET profile. There was a statistically significant negative correlation between resting DLCO, on the one hand, and dead space to tidal volume ratio and alveolar-arterial gradient [P(Ai-a)O2] on the other (p < 0.005). CPET identified 90% of patients with a mean pulmonary arterial pressure at rest ≥ 21 mmHg measured by RHC (n = 10). Peak P(Ai-a)O2, taken independently from other variables, was crucial in distinguishing subjects with ILD from those without ILD (p < 0.05). CONCLUSION: CPET is useful for the characterization of multifactorial exercise limitation in patients with SSc and in identifying SSc-related complications such as ILD and PV. This study also identifies PML as an underestimated cause of exercise limitation.


Assuntos
Tolerância ao Exercício/fisiologia , Hipertensão Pulmonar/etiologia , Doenças Pulmonares Intersticiais/etiologia , Debilidade Muscular/etiologia , Escleroderma Sistêmico/complicações , Disfunção Ventricular Esquerda/etiologia , Teste de Caminhada , Adulto , Idoso , Idoso de 80 Anos ou mais , Cateterismo Cardíaco , Dispneia , Feminino , França , Hospitais Universitários , Humanos , Hipertensão Pulmonar/diagnóstico , Doenças Pulmonares Intersticiais/diagnóstico , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/diagnóstico , Troca Gasosa Pulmonar , Testes de Função Respiratória , Estudos Retrospectivos , Estatísticas não Paramétricas , Tomógrafos Computadorizados , Disfunção Ventricular Esquerda/diagnóstico
12.
N Engl J Med ; 349(26): 2495-502, 2003 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-14695409

RESUMO

BACKGROUND: We conducted a randomized trial of the treatment of multiple myeloma with high-dose chemotherapy followed by either one or two successive autologous stem-cell transplantations. METHODS: At the time of diagnosis, 399 previously untreated patients under the age of 60 years were randomly assigned to receive a single or double transplant. RESULTS: A complete or a very good partial response was achieved by 42 percent of patients in the single-transplant group and 50 percent of patients in the double-transplant group (P=0.10). The probability of surviving event-free for seven years after the diagnosis was 10 percent in the single-transplant group and 20 percent in the double-transplant group (P=0.03). The estimated overall seven-year survival rate was 21 percent in the single-transplant group and 42 percent in the double-transplant group (P=0.01). Among patients who did not have a very good partial response within three months after one transplantation, the probability of surviving seven years was 11 percent in the single-transplant group and 43 percent in the double-transplant group (P<0.001). Four factors were significantly related to survival: base-line serum levels of beta2-microglobulin (P<0.01) and lactate dehydrogenase (P<0.01), age (P<0.05), and treatment group (P<0.01). CONCLUSIONS: As compared with a single autologous stem-cell transplantation after high-dose chemotherapy, double transplantation improves overall survival among patients with myeloma, especially those who do not have a very good partial response after undergoing one transplantation.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Dexametasona/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/mortalidade , Análise Multivariada , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida , Condicionamento Pré-Transplante , Transplante Autólogo , Vincristina/administração & dosagem
13.
Int J Cardiol ; 227: 711-716, 2017 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-27836307

RESUMO

BACKGROUND/OBJECTIVES: Cardiac sarcoidosis (CS) is associated with high morbidity and sudden death. The absence of specific symptoms and lack of diagnostic gold standard technique is challenging. New imaging methods could improve the diagnosis of CS. The aim of our study was to assess the role of left ventricular (LV) longitudinal and circumferential strain as estimated by 2D speckle-tracking imaging in patients with diagnosed sarcoidosis without cardiac involvement according to the current guidelines. We investigated the prevalence of LV strain impairment in this population and assessed its relationship with clinical outcomes, composite of mortality, heart failure, arrhythmia and/or secondarily development of CS and cardiac device implantation. METHODS AND RESULTS: We performed a prospective case-control longitudinal study including 35 patients with diagnosed sarcoidosis and normal cardiac function as assessed by standard transthoracic echocardiography and 35 healthy age- and gender-matched controls. All patients underwent a comprehensive echocardiographic study. Mean age of patients was 47.9±14.8years old (22 women). Compared with controls, global LV longitudinal strain (LV GLS) was reduced in sarcoidosis patients: (-17.2±3.1 vs -21.3±1.5%, p<0.0001). Circumferential LV strain was preserved in patients compared to controls (-19.9±-4.3% vs -21.3±1.5%, p=0.12). Impaired LV GLS was significantly associated with clinical outcomes (HR 1.56; [1.16-2.11], p<0.01) on univariate analysis. CONCLUSION: Speckle-tracking echocardiography revealed decreased longitudinal LV strain in sarcoidosis patients that was associated with outcomes. LV GLS may represent an early marker of myocardial involvement in sarcoidosis patients that needs to be studied further.


Assuntos
Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/fisiopatologia , Ecocardiografia/tendências , Sarcoidose/diagnóstico por imagem , Sarcoidose/fisiopatologia , Adulto , Estudos de Casos e Controles , Diagnóstico Precoce , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
14.
Haematologica ; 91(11): 1498-505, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17043025

RESUMO

BACKGROUND AND OBJECTIVES: Induction regimens prior to autologous stem cell transplantation (ASCT) in newly diagnosed multiple myeloma patients usually result in complete remission (CR) rates of <10%. The use of novel agents may increase the CR rate before ASCT, which may improve post-transplantation response and survival. DESIGN AND METHODS: This was a phase II, open-label trial of bortezomib (1.3 mg/m(2), days 1,4,8,11) and dexamethasone (40 mg,days 1-4 and 9-12 for cycles 1-2,days 1-4 for cycles 3-4) administered for four 21-day cycles as induction therapy in chemotherapy-naïve myeloma patients. RESULTS: Of 52 recruited patients, 48 were eligible for the study. The overall response rate was 66% including 21% CR and 10% very good partial remission (>90% reduction of the M-component). Four patients had a minimal response, six had stable disease and five had progression. One patient died after salvage therapy with VAD. The most common side effects were gastrointestinal symptoms, peripheral neuropathy, and fatigue. These were usually mild. Peripheral neuropathy was observed in 15 cases but was grade 2-3 in only seven cases (14%). There was no deep vein thrombosis and no hematologic toxicity greater than grade 2. Grade 3 infections were recorded in five patients including three who had herpes zoster infections. Stem cell collection was programmed in 44 cases and all patients had sufficient CD34+ cells to perform one ASCT (> 2 x 10(6)/kg). INTERPRETATION AND CONCLUSION: This regimen of bortezomib plus dexamethasone appears effective and well tolerated in newly diagnosed myeloma patients.


Assuntos
Ácidos Borônicos/administração & dosagem , Dexametasona/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/terapia , Pirazinas/administração & dosagem , Transplante de Células-Tronco , Adulto , Idoso , Bortezomib , Quimioterapia Combinada , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Indução de Remissão , Transplante de Células-Tronco/métodos , Transplante Autólogo
15.
Gastroenterol Clin Biol ; 30(8-9): 1093-5, 2006.
Artigo em Francês | MEDLINE | ID: mdl-17075458

RESUMO

Churg-Strauss syndrome is a rare form of severe vasculitis characterized by severe asthma and hypereosinophilia. Liver involvement is rare. We report a case of a woman with serious cholestatic hepatitis and vasculitis, without severe asthma. Marked hypereosinophilia and liver biopsy confirmed diagnosis. Churg-Strauss syndrome must be recognized because digestive involvement is very serious and affect the prognosis of this disease.


Assuntos
Colestase/etiologia , Síndrome de Churg-Strauss/diagnóstico , Hepatite/etiologia , Adulto , Feminino , Humanos
16.
J Clin Oncol ; 34(18): 2125-32, 2016 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-27114594

RESUMO

PURPOSE: Primary plasma cell leukemia (pPCL) is a rare and aggressive malignancy with a poor prognosis. With conventional chemotherapy, patients typically die within 1 year. In all but one of the retrospective studies reported to date, bortezomib and lenalidomide seem to improve survival. We conducted a prospective phase II trial in patients with pPCL to assess the efficacy of an alternate regimen that combines standard chemotherapy, a proteasome inhibitor, and high-dose melphalan and autologous stem cell transplantation (HDM/ASCT) followed by either allogeneic transplantation or bortezomib/lenalidomide maintenance. PATIENTS AND METHODS: Patients 70 years old and younger with newly diagnosed pPCL received four alternating cycles of bortezomib, dexamethasone plus doxorubicin or cyclophosphamide. Peripheral blood stem cells were collected from responding patients with < 1% of circulating plasma cells before HDM/ASCT. As consolidation, young patients received a reduced-intensity conditioning allograft, whereas the remaining patients underwent a second HDM/ASCT followed by 1 year of bortezomib, lenalidomide, dexamethasone. The primary end point was progression-free survival (PFS). RESULTS: Forty patients (median age, 57 years; range, 27 to 71 years) were enrolled. The median follow-up was 28.7 months. In the intention-to-treat analysis, the median PFS and overall survival were 15.1 (95% CI, 8.4; -) and 36.3 (95% CI, 25.6; -) months, respectively. The overall response rate to induction was 69%. One patient underwent a syngeneic allograft and 25 HDM/ASCT (16 of whom subsequently received a reduced-intensity conditioning allograft and seven a second ASCT followed by maintenance). CONCLUSION: In this prospective trial in patients with pPCL, we show that bortezomib, dexamethasone plus doxorubicin or cyclophosphamide induction followed by transplantation induces high response rates and appears to significantly improve PFS.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Leucemia Plasmocitária/terapia , Adulto , Idoso , Bortezomib/administração & dosagem , Ciclofosfamida/administração & dosagem , Dexametasona/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Humanos , Leucemia Plasmocitária/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Transplante Homólogo
17.
J Exp Med ; 213(9): 1705-22, 2016 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-27455953

RESUMO

Multiple myeloma (MM) evolves from a premalignant condition known as monoclonal gammopathy of undetermined significance (MGUS). However, the factors underlying the malignant transformation of plasmocytes in MM are not fully characterized. We report here that Eµ-directed expression of the antiapoptotic Bcl-B protein in mice drives an MM phenotype that reproduces accurately the human disease. Indeed, with age, Eµ-bcl-b transgenic mice develop the characteristic features of human MM, including bone malignant plasma cell infiltration, a monoclonal immunoglobulin peak, immunoglobulin deposit in renal tubules, and highly characteristic bone lytic lesions. In addition, the tumors are serially transplantable in irradiated wild-type mice, underlying the tumoral origin of the disease. Eµ-bcl-b plasmocytes show increased expression of a panel of genes known to be dysregulated in human MM pathogenesis. Treatment of Eµ-bcl-b mice with drugs currently used to treat patients such as melphalan and VELCADE efficiently kills malignant plasmocytes in vivo. Finally, we find that Bcl-B is overexpressed in plasmocytes from MM patients but neither in MGUS patients nor in healthy individuals, suggesting that Bcl-B may drive MM. These findings suggest that Bcl-B could be an important factor in MM disease and pinpoint Eµ-bcl-b mice as a pertinent model to validate new therapies in MM.


Assuntos
Mieloma Múltiplo/etiologia , Proteínas Proto-Oncogênicas c-bcl-2/fisiologia , Animais , Diferenciação Celular , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Hipergamaglobulinemia/etiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mieloma Múltiplo/terapia , Proteínas Proto-Oncogênicas c-bcl-2/análise , Sindecana-1/análise , Proteína bcl-X/fisiologia
19.
AIDS ; 18(9): 1321-5, 2004 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-15362665

RESUMO

OBJECTIVE: To investigate the impact of non-lipodystrophy HAART-related side effects on unprotected sexual behaviours among HIV-infected drug users. DESIGNAND PARTICIPANTS: HAART-treated patients who reported having occasional partners during the follow-up period after HAART initiation were selected among patients of the MANIF 2000 cohort of HIV-infected drug users. METHODS: Visits where patients reported unsafe sexual behaviours with occasional partners were compared to visits where they reported safe sexual behaviours using a logistic model based on Generalized Estimating Equations. RESULTS: One-hundred and ninety-two HAART-treated patients reported occasional sexual partners at least once during follow-up, accounting for a total of 464 visits. Among these 192 patients, 134 (70%) declared at least once unsafe sexual behaviours with occasional partners. During follow-up, three or more HAART-related side effects were reported in 273 of the 464 visits. When comparing visits where patients reported unsafe sexual behaviours with occasional partners (n = 249) with those where they reported safe sexual behaviours (n = 215), experiencing three or more HAART-related side effects was significantly associated with unsafe sex after adjustment for cofactors such as injecting drug status, reporting more than two sexual partners and having sex more than once a week. CONCLUSIONS: Perceived side effects play a role in determining unsafe sexual behaviours. HIV prevention interventions must consider the negative impact of HAART-related side effects on sexual risk-taking behaviours. Drug maintenance programs contribute to sexual risk reduction among drug injecting patients.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/psicologia , Sexo Seguro , Abuso de Substâncias por Via Intravenosa , Adulto , Terapia Antirretroviral de Alta Atividade , Feminino , Seguimentos , Humanos , Modelos Logísticos , Masculino , Assunção de Riscos , Parceiros Sexuais
20.
HIV Clin Trials ; 4(2): 121-31, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12671780

RESUMO

PURPOSE: The objective was to evaluate the impact of an intervention for improving adherence to antiretroviral therapies (HAART) in HIV-infected patients. METHOD: We designed a prospective, controlled, randomized trial to assess the impact of an educational and counseling intervention in addition to standard of care. At M0, the study enrolled 244 HAART-treated patients who attended a medical consultation between September and December 1999 who were not included in another protocol. Patients in the intervention group (IG) were offered three individual sessions by trained nurses. The proportions of adherent patients at 6 months followup (M6) and the change in HIV RNA between M0 and M6 were measured. RESULTS: Between M0 and M6, HIV RNA significantly decreased in the 123 patients of the IG (mean difference = -0.22 log [+/-0.86], p =.013), while it increased (+0.12 log [+/-0.90], p =.14) in the 121 patients of the control group. However, the proportion of patients with HIV RNA <40 copies/mL remained similar in both groups. In an intent-to-treat analysis, the only significant predictor of 100% adherence at M6 was the intervention group (p =.05) after adjustment for baseline adherence (p =.001). Among the 202 patients with available data on adherence, the proportion of adherent patients was similar in both groups at M0 (58% vs. 63%, p =.59) but became higher in the IG at M6 (75% vs. 61%, p =.04). CONCLUSION: The educational and counseling intervention was efficient for increasing adherence to HAART and could be implemented in most clinical settings.


Assuntos
Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Cooperação do Paciente , Educação de Pacientes como Assunto , Adulto , Feminino , França , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Inquéritos e Questionários
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