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1.
Eur J Haematol ; 99(1): 80-90, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28384387

RESUMO

INTRODUCTION: Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant condition with a risk of malignant conversion. PATIENTS AND METHODS: With the aim to estimate the cumulative risk MGUS progression to hematologic malignancies, we analyzed a nationwide population-based cohort of 1887 MGUS patients from the Czech Registry of Monoclonal Gammopathies (RMG) between 2007 and 2013. RESULTS: During the follow-up period (median 4 years; range 0.6-34.8), progression to hematologic malignancies was observed in 8.6% (162 of 1887) of patients. Factors associated with progression were as follows: M-protein concentration ≥1.5 g/dL, pathological sFLC (<0.26 or >1.65) ratio, bone marrow plasma cells (BMPCs) in cytology >5%, immunoparesis, age ≥69 years, and the level of serum hemoglobin at baseline <12.0 g/dL. Combining these factors, we propose a new risk model (CMG model). The risk of progression at 10 years was 1.6%, 16.9%, 22.9%, 39.4%, and 52.3%, respectively, if 0 (reference group), one, two, three, or four to five risk factors are present (P<.001) with HR 63 times higher compared to the reference MGUS group. CONCLUSION: The new CMG model was established with an advantage for better identification of MGUS patients at low risk.


Assuntos
Gamopatia Monoclonal de Significância Indeterminada/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Medula Óssea/patologia , Transformação Celular Neoplásica , República Tcheca/epidemiologia , Progressão da Doença , Feminino , Humanos , Hibridização in Situ Fluorescente , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Gamopatia Monoclonal de Significância Indeterminada/metabolismo , Proteínas do Mieloma/metabolismo , Plasmócitos/metabolismo , Plasmócitos/patologia , Vigilância da População , Modelos de Riscos Proporcionais , Sistema de Registros , Medição de Risco , Fatores de Risco
2.
Haematologica ; 99(2): 360-4, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24038024

RESUMO

Even in the era of new drugs, multiple myeloma patients with extramedullary relapse have a poor prognosis. Our goal was to analyze the frequency and outcome of extramedullary relapse occurring in relapsed multiple myeloma patients. In total, we analyzed the prognosis of 226 relapsed multiple myeloma patients treated between 2005 and 2008 and evaluated them for presence of extramedullary relapse. We found evidence of extramedullary relapse in 24% (55 of 226) of relapsed multiple myeloma patients. In 14% (32 of 226) of patients, the lesions were not adjacent to the bone, while extramedullary relapse adjacent to the bone was documented in 10% (23 of 226) of cases. Patients without extramedullary relapse had significantly longer overall survival than patients with extramedullary relapse (109 vs. 38 months; P<0.001). Moreover, patients with soft tissue-related extramedullary relapse had significantly poorer overall survival compared to bone-related extramedullary relapse patients (30 vs. 45 months; P=0.022). Also, overall survival from diagnosis was as low as five months for soft tissue-related extramedullary relapse patients when compared to 12 months overall survival for bone-related extramedullary relapse. This is the first study that shows a significant difference in prognosis for different types of extramedullary relapse. If the extramedullary myeloma infiltration was not bone-related, overall survival after relapse was extremely short (5 months).


Assuntos
Neoplasias Ósseas , Mieloma Múltiplo , Neoplasias de Tecidos Moles , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Neoplasias Ósseas/secundário , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/terapia , Estudos Retrospectivos , Fatores de Risco , Neoplasias de Tecidos Moles/mortalidade , Neoplasias de Tecidos Moles/secundário , Neoplasias de Tecidos Moles/terapia , Taxa de Sobrevida
3.
Ann Hematol ; 90(12): 1441-7, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21380511

RESUMO

Many regimens containing novel drugs have been developed for multiple myeloma (MM). It is not yet clear whether some of the novel agents are better than others. In a retrospective study, we have analyzed the outcomes of patients with first relapse of MM treated with thalidomide-based (T) regimens (n=105) or bortezomib-based (B) regimens (n=106). Both T and B groups were comparable regarding basic clinical parameters and first-line therapies. Combination of thalidomide with an alkylating drug (A) and dexamethasone (D) was used in 91 cases, T with D in five cases, and T alone in nine cases. A combination of bortezomib with A and D was used in 58 patients, B with D or A in 40 patients, and B alone in eight patients. In the T group, ORR was 51%, median TTP from the start of treatment for relapse of 13.1 months, and median OS of 30.4 months. In the B group, ORR was 50% with median TTP of 16.7 months and median OS of 37.2 months. No significant differences in ORR (p=0.774), TTP (p=0.207), or OS (p=0.889) were observed between the two groups. In conclusion, T- and B-based regimens appear to be equally effective in the treatment of first MM relapse.


Assuntos
Antineoplásicos/uso terapêutico , Ácidos Borônicos/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/prevenção & controle , Pirazinas/uso terapêutico , Talidomida/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib , Dexametasona/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
4.
Biol Blood Marrow Transplant ; 16(4): 548-54, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20005965

RESUMO

The prognostic significance of 1q21 gain, del(13)(q14), del(17)(p13), t(4;14)(p16.3;q32), and t(11;14)(q13;q32) detected by interphase fluorescein in situ hybridization (FISH) was studied in a cohort of 91 patients with newly diagnosed multiple myeloma (MM). 1q21 gain was detected in 37 of 91 patients (40.7%). In comparison with patients lacking 1q21 gain, patients with 1q21 gain had significantly shorter progression-free survival (PFS) (14.9 versus 27.4 months; P = .044) and worse 4-year overall survival (OS) (40.1% versus 76.2% of patients; P = <.001). PFS or OS were not influenced by the presence or absence of the other studied chromosomal abnormalities. Although the occurrence of 1q21 gain correlated with deletion of 13q14, the presence of 1q21 gain can be considered an independent prognostic factor, as no impact of del(13)(q14) as an isolated chromosomal abnormality on either PFS or OS has been observed. In comparison with patients lacking 1q21 gain, patients with 1q21 gain were significantly more likely to discontinue the preplanned treatment protocol because of disease progression or death. We conclude that 1q21 gain defines a prognostically unfavorable group of MM patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Aberrações Cromossômicas , Cromossomos Humanos Par 1 , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/genética , Adulto , Idoso , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida
5.
Ann Hematol ; 89(5): 483-7, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-19924414

RESUMO

Patients (pts) with fulminant progression (FPG) of multiple myeloma (MM) after autologous stem cell transplantation (ASCT) have poor prognosis. Pancytopenia, extramedullary disease, and/or renal impairment are often present, and treatment options are limited. We have retrospectively evaluated 31 pts with FPG of MM after ASCT who were treated upfront salvage therapy with melphalan 100 mg/m(2) (MEL 100) followed by PBSC support and consolidation therapy using regimens containing thalidomide (n = 16) or bortezomib (n = 15). The overall response rate (ORR) was 58% (18/31). After MEL 100, one patient achieved complete remission (3%), 26% of pts very good partial remission, 29% of pts partial remission, and 42% of pts stable disease. Progression within 3 months after MEL 100 occurred in 35% of pts. The median follow-up from MEL 100 was 8 months. The median TTP was 5 months (range, 2-15 months), and the median OS was 8 months (range, 3-23 months). There were no treatment-related deaths. In fulminant progression of MM, upfront MEL 100 is a safe salvage regimen with good response rate (ORR, 58%). Treatment with upfront MEL 100 followed by a thalidomide- or bortezomib-based regimen can prolong overall survival to more than 12 months in 33% of pts with fulminant progression of MM.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Progressão da Doença , Mieloma Múltiplo/tratamento farmacológico , Terapia de Salvação , Adulto , Idoso , Esquema de Medicação , Seguimentos , Humanos , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Estudos Retrospectivos , Terapia de Salvação/métodos , Resultado do Tratamento
6.
Clin Lymphoma Myeloma ; 9(2): 151-3, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19406726

RESUMO

BACKGROUND: Varicella-zoster virus (VZV) reactivation is a common complication in patients with multiple myeloma (MM) treated with bortezomib, with an incidence rate of 10%-60%. The aim of our study was to analyze the effect of acyclovir prophylaxis in this patient population. PATIENTS AND METHODS: We studied 98 consecutive patients with relapsed MM treated with bortezomib. Bortezomib 1.3 mg/m2 was given on days 1, 4, 8, and 11 of a 21-day cycle. At first, patients did not receive any VZV prophylaxis, but because of the high incidence of VZV reactivation, VZV prophylaxis with acyclovir was implemented subsequently. RESULTS: A total of 11 patients treated with bortezomib did not have any VZV prophylaxis, and 4 of these 11 patients (36%) developed VZV reactivation in the form of herpes zoster. No VZV reactivations were observed in the 32 patients who received acyclovir 400 mg 3 times daily or the 55 patients who received acyclovir in a dose reduced to 400 mg once daily during bortezomib treatment. CONCLUSION: Varicellazoster virus reactivation is a common and serious adverse effect of bortezomib treatment. Acyclovir 400 mg once daily is sufficient to protect from VZV reactivation in patients with MM treated with bortezomib.


Assuntos
Aciclovir/uso terapêutico , Antineoplásicos/uso terapêutico , Ácidos Borônicos/uso terapêutico , Herpes Zoster/prevenção & controle , Herpesvirus Humano 3/fisiologia , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/virologia , Pirazinas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Antivirais/uso terapêutico , Ácidos Borônicos/efeitos adversos , Bortezomib , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Pirazinas/efeitos adversos , Ativação Viral/efeitos dos fármacos
8.
Biomed Res Int ; 2014: 209670, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24987674

RESUMO

Characteristic recurrent copy number aberrations (CNAs) play a key role in multiple myeloma (MM) pathogenesis and have important prognostic significance for MM patients. Array-based comparative genomic hybridization (aCGH) provides a powerful tool for genome-wide classification of CNAs and thus should be implemented into MM routine diagnostics. We demonstrate the possibility of effective utilization of oligonucleotide-based aCGH in 91 MM patients. Chromosomal aberrations associated with effect on the prognosis of MM were initially evaluated by I-FISH and were found in 93.4% (85/91). Incidence of hyperdiploidy was 49.5% (45/91); del(13)(q14) was detected in 57.1% (52/91); gain(1)(q21) occurred in 58.2% (53/91); del(17)(p13) was observed in 15.4% (14/91); and t(4;14)(p16;q32) was found in 18.6% (16/86). Genome-wide screening using Agilent 44K aCGH microarrays revealed copy number alterations in 100% (91/91). Most common deletions were found at 13q (58.9%), 1p (39.6%), and 8p (31.1%), whereas gain of whole 1q was the most often duplicated region (50.6%). Furthermore, frequent homozygous deletions of genes playing important role in myeloma biology such as TRAF3, BIRC1/BIRC2, RB1, or CDKN2C were observed. Taken together, we demonstrated the utilization of aCGH technique in clinical diagnostics as powerful tool for identification of unbalanced genomic abnormalities with prognostic significance for MM patients.


Assuntos
Aberrações Cromossômicas , Hibridização Genômica Comparativa/métodos , Estudo de Associação Genômica Ampla , Mieloma Múltiplo/genética , Proteínas de Neoplasias/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , República Tcheca , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Prognóstico
9.
PLoS One ; 7(10): e47077, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23071717

RESUMO

BACKGROUND: Regulatory T (Treg) cells play an important role in the maintenance of immune system homeostasis. Multiple myeloma (MM) is a plasma cell disorder frequently associated with impaired immune cell numbers and functions. METHODS: We analyzed Treg cells in peripheral blood (n = 207) and bone marrow (n = 202) of pre-malignant and malignant MM patients using flow cytometry. Treg cells and their subsets from MM patients and healthy volunteers were functionally evaluated for their suppressive property. A cohort of 25 patients was analyzed for lymphocytes, CD4 T cells and Treg cells before and after treatment with cyclophosphamide, thalidomide plus dexamethasone (CTD). RESULTS: We found elevated frequencies of Treg cells in newly diagnosed (P<0.01) and relapsed MM patients (P<0.0001) compared to healthy volunteers. Also, Treg subsets including naïve (P = 0.015) and activated (P = 0.036) Treg cells were significantly increased in MM patients compared to healthy volunteers. Functional studies showed that Treg cells and their subsets from both MM and healthy volunteers were similar in their inhibitory function. Significantly increased frequencies of Treg cells were found in MM patients with adverse clinical features such as hypercalcemia (>10 mg/dL), decreased normal plasma cell (≤5%) count and IgA myeloma subtype. We also showed that MM patients with ≥5% of Treg cells had inferior time to progression (TTP) (13 months vs. median not reached; P = 0.013). Furthermore, we demonstrated the prognostic value of Treg cells in prediction of TTP by Cox regression analysis (P = 0.045). CTD treatment significantly reduced frequencies of CD4 T cells (P = 0.001) and Treg cells (P = 0.018) but not Treg cells/CD4 T cells ratio compared to pre-treatment. CONCLUSIONS: Our study showed immune deregulation in MM patients which is evidenced by elevated level of functionally active Treg cells and patients with increased Treg cells have higher risk of progression.


Assuntos
Mieloma Múltiplo/patologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Estudos de Casos e Controles , Ciclofosfamida/uso terapêutico , Dexametasona/uso terapêutico , Progressão da Doença , Feminino , Humanos , Hipercalcemia/etiologia , Hipercalcemia/patologia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/imunologia , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Valores de Referência , Subpopulações de Linfócitos T/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Talidomida/uso terapêutico
10.
Nucl Med Biol ; 39(3): 429-36, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22172385

RESUMO

INTRODUCTION: Pulmonary Langerhans cell histiocytosis (PLCH) is a rare cause of interstitial lung disease characterized by formation of nodules in the active phase of the disease that evolve into nonactive cystic lesions later on. To evaluate PLCH activity in patients, we developed a new method for measuring diffuse metabolic activity on fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) using a lung-to-liver activity ratio. MATERIAL AND METHODS: We retrospectively studied a series of 4 FDG-PET and 23 FDG-PET/CT scans from 7 patients with PLCH and analyzed a sample of 100 randomly chosen FDG-PET/CT studies free from any known lung or hepatic diseases. Maximum standardized uptake value (SUVmax) in a spherical volume (6-8 cm in diameter) in the right lung was put into relation with SUVmax in a spherical volume (9-10 cm in diameter) in the reference liver parenchyma to set up the SUVmaxPULMO/SUVmaxHEPAR index. The index values were compared to the disease course in each patient. RESULTS: In patients with PLCH, a close correlation between the index value and the disease course was found in all seven subjects, where the increasing index values indicated disease activity, while decreasing index values were observed after therapy administration. In the group of 100 healthy control subjects, we found index values lower than 0.3 in 80% and lower than 0.4 in 96% [range: 0.14-0.43; 0.24±0.07 (100)]. CONCLUSION: Measuring SUVmaxPULMO/SUVmaxHEPAR values and their time-trend monitoring represent simple, noninvasive screening tools allowing an early diagnosis and treatment response follow-up assessment in patients with PLCH.


Assuntos
Fluordesoxiglucose F18 , Histiocitose de Células de Langerhans/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Feminino , Seguimentos , Histiocitose de Células de Langerhans/diagnóstico , Histiocitose de Células de Langerhans/terapia , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Prognóstico , Compostos Radiofarmacêuticos , Testes de Função Respiratória , Estudos Retrospectivos
11.
Clin Lymphoma Myeloma ; 9(6): 436-42, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19951883

RESUMO

BACKGROUND: Autologous stem cell transplantation (autoSCT) has an important role in the treatment of patients with symptomatic multiple myeloma (MM). Treatment options for myeloma have expanded in the past decade, and it seems that patients who are treated with novel drugs such as thalidomide and bortezomib for relapse after autoSCT have longer overall survival (OS). PATIENTS AND METHODS: Herein, we describe the long-term outcome of a cohort of 185 patients with newly diagnosed MM treated with autoSCT. We have analyzed factors that might predict for long-term survival. RESULTS: Following autoSCT, the overall response rate was 94% (173 of 185 patients); 29% (53 of 185 patients) were in complete remission (CR). Median time to progression (TTP) and OS from start of therapy were 39.8 months and 77.9 months, respectively. The median follow-up was 103.8 months (range, 60.8-144.8 months); 23% of the patients are alive and disease free, 21% of the patients are alive with relapse, and 56% of the patients have died. On multivariate analysis, factors associated with significantly better OS were International Staging System (ISS) disease stage < III (hazard ratio [HR], 2.6; P < .001), achievement of CR after autoSCT (HR, 2.8; P < .001) and use of thalidomide (HR, 4.3; P < .001) and/or bortezomib (HR, 7.3; P < .001) in posttransplantation relapse treatment. The patients' age, renal impairment, disease status before autoSCT and maintenance therapy with interferon-alpha (IFN-alpha) or IFN-alpha and dexamethasone did not significantly affect TTP and OS after transplantation. CONCLUSION: According to our results, the achievement of CR after transplantation, ISS stage other than III, and administration of thalidomide or bortezomib in posttransplantation relapse were significant parameters favoring long-term posttransplantation survival.


Assuntos
Ácidos Borônicos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/terapia , Pirazinas/uso terapêutico , Talidomida/uso terapêutico , Adulto , Idoso , Bortezomib , Progressão da Doença , Humanos , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Recidiva , Transplante Autólogo , Resultado do Tratamento
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