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1.
Eur J Haematol ; 102(5): 389-394, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30719772

RESUMO

OBJECTIVE: The presence of plasmacytomas (Ps) in patients with multiple myeloma (MM) is associated with a poor outcome, both in patients treated conventionally and in patients treated with novel agents. Two types of plasmacytomas have being recognized: paraskeletal plasmacytomas (PPs) and extramedullary plasmacytomas (EMPs), being the incidence of EMPs lower but with worse prognosis. Our aim has been to analyze the efficacy of the pomalidomide-dexamethasone combination in this patient profile. METHOD: In the present study, the efficacy of pomalidomide and dexamethasone in 21 patients from nine hospitals of Catalonia (Spain), with relapsed or refractory MM and Ps, was analyzed. For this purpose, we describe the evolution of paraprotein in serum and urine and the size of plasmacytomas during treatment with pomalidomide-dexamethasone. RESULTS: While 34% of the patients achieved a paraprotein response, only two patients with PPs (9%) responded (RC and PR). There were no responses among patients with EMPs. The median progression-free survival from the start of treatment with pomalidomide/dexamethasone was only 1.7 months and the median overall survival of 4.5 months. CONCLUSION: In conclusion, pomalidomide and dexamethasone has limited efficacy in patients with advanced MM and soft-tissue plasmacytomas.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/complicações , Plasmocitoma/complicações , Plasmocitoma/tratamento farmacológico , Neoplasias de Tecidos Moles/complicações , Neoplasias de Tecidos Moles/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Dexametasona/administração & dosagem , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Mieloma Múltiplo/diagnóstico , Recidiva Local de Neoplasia , Plasmocitoma/diagnóstico , Neoplasias de Tecidos Moles/diagnóstico , Talidomida/administração & dosagem , Talidomida/análogos & derivados
2.
Bone Marrow Transplant ; 54(8): 1295-1303, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30664727

RESUMO

Autologous stem cell transplant (ASCT) has demonstrated to be an effective treatment for patients with light-chain (AL) amyloidosis. However, a high transplant-related mortality (TRM) rate was reported in previous series of patients and questioned the role of transplant in this disease. Recently, experienced groups have shown a significant TRM decrease that has been attributed to an accurate selection of patients. Moreover, application of several supportive measures has decreased toxicity over amyloid-involved organs. We analyzed a series of 66 patients with AL amyloidosis, who underwent ASCT at a single institution and evaluated the impact of these measures beyond patient selection. Four temporary groups were established: group-A (non-selection plus post-transplant G-CSF use) with 29 patients, group-B (selection) with 13, group-C (selection and G-CSF avoidance) with 14, and group-D (selection, G-CSF avoidance and corticosteroid's prophylaxis) with 10. A decreasing TRM was observed over time from group-A (38%), to group-D (0%); p = 0.02. We also observed a progressive increase of three-year OS from 62% in group-A to 100% in group-D; p = 0.049. On the multivariate analysis, cardiac involvement was the only independent predictor of survival. Therefore, tailored selection policy together with transplant supportive measures have allowed ASCT to be a safe procedure in AL amyloidosis.

3.
Int J Mol Sci ; 19(11)2018 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-30445802

RESUMO

Multiple myeloma (MM) remains an incurable hematological malignancy characterized by clonal proliferation of malignant plasma cells in bone marrow. In the last 20 years, the introduction of autologous stem cell transplantation, followed by proteasome inhibitors and immunomodulatory agents, increased the survival of MM patients by 50%. However, still a high proportion of patients relapse and become refractory, especially, high-risk patients with adverse cytogenetics where these treatment combinations have shown limited benefit. Therefore, novel strategies, such as immunotherapy, have been developed in the last few years to help improve the survival of these patients. Immunotherapy treatments include a high number of different strategies used to attack the tumor cells by using the immune system. Here, we will review the most successful immunotherapy strategies published up to date in patients with relapsed or refractory (R/R) MM, including monoclonal antibodies targeting specific antigens on the tumor cells, antibodies combined with cytotoxic drugs or Antibodies Drug Conjugates, immune checkpoint inhibitors which eliminate the barriers that damper immune cells and prevent them from attacking tumor cells, bi-specific T-cell engagers antibodies (BiTEs), bi-specific antibodies and the infusion of chimeric antigen receptor-modified T cells. We overview the results of clinical studies that have been presented up to date and also review pre-clinical studies describing potential novel treatments for MM.


Assuntos
Imunoterapia , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/terapia , Animais , Antígeno de Maturação de Linfócitos B/metabolismo , Ensaios Clínicos como Assunto , Humanos , Imunoterapia Adotiva
4.
J Clin Oncol ; 36(20): 2012-2016, 2018 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-29851545

RESUMO

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 45-year-old man was diagnosed in March 2010 with stage III immunoglobulin G kappa multiple myeloma (MM) after presenting with bone pain as a result of multiple lytic bone lesions and T12 vertebral collapse. Laboratory work-up showed a serum M protein of 72 g/L and a 24-hour kappa light-chain urine protein excretion of 730 mg, hemoglobin of 10.2 g/dL, serum albumin of 49 g/L, serum ß2-microglobulin of 6.4 mg/L, serum creatinine level of 1.6 mg/dL with an estimated glomerular filtration rate (eGFR) of 47 mL/min/1.73 m2, and normal serum calcium and lactate dehydrogenase (LDH) levels. His bone marrow contained 58% plasma cells, which showed the 17p deletion abnormality (Fig 1). He was treated with vertebroplasty and alternating chemotherapy with carmustine, vincristine, cyclophosphamide, melphalan, and prednisone and vincristine, carmustine, doxorubicin and dexamethasone. Because of progressive disease, salvage therapy with bortezomib and dexamethasone was administered with no response. The patient was then switched to lenalidomide and dexamethasone, which yielded minimal response. He underwent autologous stem-cell transplantation (ASCT) with melphalan 200 mg/m2 as high-dose therapy in February 2011, which led to a partial response, but in December 2011, progressive disease was documented, and the patient was enrolled in a clinical trial of carfilzomib monotherapy, with stable disease for 33 cycles. In October 2014 serum M protein rose to 38.6 g/L, with 24-hour kappa light-chain urine protein excretion of 840 mg, serum creatinine of 2.1 mg/dL, and an eGFR of 41 mL/min/1.73 m2. He presented to discuss ongoing treatment options.


Assuntos
Mieloma Múltiplo , Insuficiência Renal , Protocolos de Quimioterapia Combinada Antineoplásica , Dexametasona , Humanos , Masculino , Pessoa de Meia-Idade , Talidomida/análogos & derivados
6.
J Immunol ; 200(8): 2581-2591, 2018 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-29531171

RESUMO

Mechanisms of immune regulation may control proliferation of aberrant plasma cells (PCs) in patients with monoclonal gammopathy of undetermined significance (MGUS) preventing progression to active multiple myeloma (MM). We hypothesized that CD85j (LILRB1), an inhibitory immune checkpoint for B cell function, may play a role in MM pathogenesis. In this study, we report that patients with active MM had significantly lower levels of CD85j and its ligand S100A9. Decreased CD85j expression could also be detected in the premalignant condition MGUS, suggesting that loss of CD85j may be an early event promoting tumor immune escape. To gain insight into the molecular mechanisms underlying CD85j functions, we next enforced expression of CD85j in human myeloma cell lines by lentiviral transduction. Interestingly, gene expression profiling of CD85j-overexpressing cells revealed a set of downregulated genes with crucial functions in MM pathogenesis. Furthermore, in vitro functional assays demonstrated that CD85j overexpression increased susceptibility to T cell- and NK-mediated killing. Consistently, ligation of CD85j decreased the number of PCs from individuals with MGUS but not from patients with MM. In conclusion, downregulation of inhibitory immune checkpoints on malignant PCs may provide a novel mechanism of immune escape associated with myeloma pathogenesis.


Assuntos
Antígenos CD/imunologia , Receptor B1 de Leucócitos Semelhante a Imunoglobulina/imunologia , Mieloma Múltiplo/imunologia , Plasmócitos/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos B , Linhagem Celular Tumoral , Regulação para Baixo/imunologia , Feminino , Humanos , Células Matadoras Naturais/imunologia , Masculino , Pessoa de Meia-Idade , Linfócitos T/imunologia , Transcriptoma/imunologia
7.
Amyloid ; 25(2): 79-85, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29482381

RESUMO

OBJECTIVES: Prognosis of immunoglobulin light-chain (AL) amyloidosis depends mainly on the presence of cardiac involvement and the disease burden. A higher bone marrow plasma cell (BMPC) burden has been recognized as an adverse prognostic factor. The aim of our study was to analyze the correlation between the BMPC infiltration, clinical features and outcomes in patients with AL amyloidosis. METHODS: The clinical records of 79 patients with AL amyloidosis treated at a single institution. RESULTS: Median BMPC infiltration at diagnosis was 11% and significantly correlated with the serum free light-chain difference (p < .001). Patients with more than 10% BMPCs had more frequent cardiac involvement (86 vs. 63%; p = .015), a trend towards a higher early mortality (27 vs. 11%; p = .08) and a significantly shorter progression-free survival (PFS) (median of 18 vs. 48 months, p = .02) and overall survival (median of 33 months vs. not reached; p = .046). In the multivariate analysis, a BMPC infiltration over 10% retained its adverse prognostic value for PFS (HR = 2.26; 95% CI, 1.048-4.866; p = .038). The use of new drugs seemed to overcome the negative prognostic impact of a higher BMPC infiltration. CONCLUSION: Higher BMPC infiltration in AL amyloidosis might be associated with increased systemic organ damage, particularly cardiac involvement and is rarely related to the development of myeloma features.


Assuntos
Amiloidose/patologia , Amiloidose de Cadeia Leve de Imunoglobulina/patologia , Plasmócitos/patologia , Idoso , Amiloidose/diagnóstico , Amiloidose/mortalidade , Feminino , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico , Amiloidose de Cadeia Leve de Imunoglobulina/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
8.
Leukemia ; 32(6): 1427-1434, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29463830

RESUMO

Smoldering multiple myeloma (SMM) is a biologically heterogeneous, clinically defined entity with a variable rate of progression to symptomatic multiple myeloma (MM). Reliable markers for progression are critical for the development of potential therapeutic interventions. We retrospectively evaluated the predictive value of the evolving pattern of serum M-protein among other progression risk factors in 206 patients with SMM diagnosed between 1973 and 2012. Median time from recognition of evolving type to progression into symptomatic MM was 1.1 years (95% CI 0.5-2.0) and progression rate at 3 years was 71%. Development of the evolving type drastically worsened the prognostic estimation made at diagnosis for every covariate predictive of progression (serum M-protein size, bone marrow plasma cell infiltration, immunoparesis and Mayo Clinic risk). On average, the hazard ratio for progression to symptomatic MM increased to 5.1 (95% CI 3.4-7.6) after recognition of the evolving type. In conclusion, in patients with SMM the evolving pattern accurately predicts the risk of early progression to symptomatic disease, thereby allowing the identification of ultra-high risk patients who would be candidates for immediate therapy.


Assuntos
Proteínas do Mieloma/análise , Mieloma Múltiplo Latente/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Mieloma Múltiplo Latente/mortalidade
9.
Amyloid ; 24(4): 245-252, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29052436

RESUMO

OBJECTIVES: Immunoparesis (IP) is a risk factor associated with an unfavourable outcome in several plasma cell disorders. It has been suggested that its presence in light-chain (AL) amyloidosis could be associated with worse prognosis. However, the relevance of IP after treatment has not been evaluated to date. The aim of this study was to determine the prognostic impact of IP at diagnosis and one year after treatment onset in patients with AL amyloidosis. METHODS: The clinical records of 69 patients with AL amyloidosis treated at a single institution from January 2006 to January 2016 were included in the study. RESULTS: IP was observed in 27.5% of patients at diagnosis. The presence of IP was associated with a lower probability to achieve very good partial response or better after first-line treatment (37.8% versus 62.2%; p = .04). However, only in the group of patients treated with autologous stem cell transplantation (ASCT), the presence of IP resulted in a shorter progression-free survival (PFS) (30.2 months versus not reached [NR]; p = .02) but not in overall survival (OS). Persistence of IP at one year after treatment onset was identified in only four (9.8%) of the 41 evaluable patients. In the ASCT group, the absence of IP at one year after treatment onset resulted in a longer median PFS and OS (NR versus 22.6 months; p = .006; and NR versus 35.2 months; p < .001; respectively). In the multivariate analysis, the absence of IP at one year after treatment onset was independently associated with longer survival. CONCLUSION: IP at diagnosis has a negative impact on survival while its absence at one year after treatment is an independent marker for long-term survival.


Assuntos
Amiloidose de Cadeia Leve de Imunoglobulina , Transplante de Células-Tronco , Idoso , Autoenxertos , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico , Amiloidose de Cadeia Leve de Imunoglobulina/imunologia , Amiloidose de Cadeia Leve de Imunoglobulina/mortalidade , Amiloidose de Cadeia Leve de Imunoglobulina/terapia , Masculino , Pessoa de Meia-Idade , Plasmócitos/imunologia , Plasmócitos/patologia , Fatores de Risco , Taxa de Sobrevida
11.
Biol Blood Marrow Transplant ; 23(8): 1269-1275, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28434927

RESUMO

The emergence of oligoclonal bands (OB) in patients with multiple myeloma achieving a complete remission (CR) after autologous stem cell transplantation (ASCT) and the use of novel agents is a well-recognized event. The presence of OB is associated with favorable outcome. However, the emergence of OB in light-chain (AL) amyloidosis has never been investigated. The aim of the study was to determine the incidence, natural history, and prognostic impact of OB in 50 patients with AL amyloidosis who achieved at least a partial response either after upfront ASCT (20 patients [40%]) or after conventional treatment in patients ineligible for transplantation (30 patients [60%]). OB were observed in 60% of the patients, with IgG-kappa (30.7%) the most frequently detected isotype. This phenomenon was more prevalent in patients achieving CR than those in other response categories (88% versus 32%, P = .0001). The landmark analysis at 1 year after diagnosis demonstrates a significantly longer progression-free survival and an improvement trend in overall survival (P = .04 and P = .06, respectively). This prognostic impact was also observed in patients who achieved CR and in patients with more advanced stage. In summary, this is the first report of OB in patients with AL amyloidosis. Although its biological meaning remains unclear, it could reflect a more robust humoral immune response.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Amiloidose de Cadeia Leve de Imunoglobulina , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoenxertos , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/sangue , Amiloidose de Cadeia Leve de Imunoglobulina/mortalidade , Amiloidose de Cadeia Leve de Imunoglobulina/terapia , Incidência , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida
15.
Clin Lymphoma Myeloma Leuk ; 16(6): e71-7, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27013181

RESUMO

BACKGROUND: Asymptomatic monoclonal gammopathies, such as monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma (SMM), are clinical conditions that usually precede symptomatic multiple myeloma. Therefore, risk stratification is crucial owing to the heterogeneous progression rate among these patients. In previous years, suppression of the uninvolved chain of specific heavy/light chain (HLC) pairs in serum has been identified as a new risk factor in MGUS. The aim of the present study was to investigate the prognostic effect of involved and uninvolved HLC pairs and HLC ratios on progression in a series of patients with MGUS and SMM. PATIENTS AND METHODS: All specific serum HLC pairs were measured in 114 patients diagnosed with SMM (n = 27) and MGUS (n = 87) from 1983 to 2003. Also, the HLC ratios were calculated. RESULTS: Progression to symptomatic multiple myeloma was observed in 13 patients (8 with SMM and 5 with MGUS). The risk of progression was 6 times greater in those with SMM (P = .001) and 4 times greater for those with the IgA isotype (P = .01). The suppression of any IgM isotypes (IgMκ or IgMλ) in patients with IgA or IgG gammopathy or any IgA isotypes (IgAκ or IgAλ) in patients with IgG or IgM gammopathy was associated with a shorter time to progression to symptomatic gammopathy (P = .001 and P = .03, respectively). On multivariate analysis, the evolving pattern and suppression of any IgM HLC pair remained significant. CONCLUSION: HLC ratios could be a valuable tool in the risk stratification of patients with SMM and MGUS, especially patients with IgG isotypes.


Assuntos
Cadeias Pesadas de Imunoglobulinas/sangue , Cadeias Leves de Imunoglobulina/sangue , Gamopatia Monoclonal de Significância Indeterminada/sangue , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Paraproteinemias/sangue , Paraproteinemias/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Medula Óssea/patologia , Progressão da Doença , Feminino , Seguimentos , Humanos , Isotipos de Imunoglobulinas/sangue , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Mieloma Múltiplo/diagnóstico , Avaliação de Resultados da Assistência ao Paciente , Prognóstico , Fatores de Risco
16.
Oncologist ; 21(3): 333-42, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26921288

RESUMO

Smoldering multiple myeloma (SMM) is an asymptomatic clonal plasma cell disorder and bridges monoclonal gammopathy of undetermined significance to multiple myeloma (MM), based on higher levels of circulating monoclonal immunoglobulin and bone marrow plasmocytosis without end-organ damage. Until a Spanish study reported fewer MM-related events and better overall survival among patients with high-risk SMM treated with lenalidomide and dexamethasone, prior studies had failed to show improved survival with earlier intervention, although a reduction in skeletal-related events (without any impact on disease progression) has been described with bisphosphonate use. Risk factors have now been defined, and a subset of ultra-high-risk patients have been reclassified by the International Myeloma Working Group as MM, and thus will require optimal MM treatment, based on biomarkers that identify patients with a >80% risk of progression. The number of these redefined patients is small (∼10%), but important to unravel, because their risk of progression to overt MM is substantial (≥80% within 2 years). Patients with a high-risk cytogenetic profile are not yet considered for early treatment, because groups are heterogeneous and risk factors other than cytogenetics are deemed to weight higher. Because patients with ultra-high-risk SMM are now considered as MM and may be treated as such, concerns exist that earlier therapy may increase the risk of selecting resistant clones and induce side effects and costs. Therefore, an even more accurate identification of patients who would benefit from interventions needs to be performed, and clinical judgment and careful discussion of pros and cons of treatment initiation need to be undertaken. For the majority of SMM patients, the standard of care remains observation until development of symptomatic MM occurs, encouraging participation in ongoing and upcoming SMM/early MM clinical trials, as well as consideration of bisphosphonate use in patients with early bone loss.


Assuntos
Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/sangue , Dexametasona/uso terapêutico , Difosfonatos/uso terapêutico , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Talidomida/análogos & derivados , Progressão da Doença , Europa (Continente) , Humanos , Cadeias Leves de Imunoglobulina/sangue , Lenalidomida , Mieloma Múltiplo/patologia , Proteínas do Mieloma/análise , Fatores de Risco , Talidomida/uso terapêutico , Carga Tumoral
17.
Br J Haematol ; 170(6): 804-13, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25974382

RESUMO

Immunomodulatory drugs have been shown to be of benefit in relapsed/refractory immunoglobulin light-chain (AL) amyloidosis. We designed a prospective, multicentre phase II trial of lenalidomide, dexamethasone and cyclophosphamide for newly diagnosed patients with AL amyloidosis not eligible for autologous stem-cell transplantation. Twenty-eight patients were included in the study. Cardiac involvement was present in 23 patients; 14 of them had cardiac stage III. The overall haematological response rate was 46%, including complete and very good partial responses in 25% and 18% of patients respectively. Haematological response was mainly associated with absence of cardiac stage III and lower tumour burden. Organ response was observed in 46% of patients. After a median follow-up of 24 months, median progression-free and overall survival have not been reached, both being significantly longer in responders (P < 0·001 and P = 0·001 respectively). Seventeen patients have discontinued treatment, mostly due to amyloid-related death, disease progression or lack of response. Only 14% of the patients discontinued treatment due to therapy-related adverse events. Our results support the efficacy of this regimen, with high quality responses and prolonged survival, as well as its tolerability, in patients with AL amyloidosis not eligible for stem cell transplant and without advanced cardiac involvement (clinicaltrials.gov identifier: NCT01194791).


Assuntos
Amiloidose/tratamento farmacológico , Amiloidose/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cadeias Leves de Imunoglobulina/metabolismo , Idoso , Idoso de 80 Anos ou mais , Amiloidose/diagnóstico , Amiloidose/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/administração & dosagem , Dexametasona/administração & dosagem , Progressão da Doença , Feminino , Humanos , Lenalidomida , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Talidomida/administração & dosagem , Talidomida/análogos & derivados , Resultado do Tratamento
19.
Blood ; 125(14): 2239-44, 2015 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-25636337

RESUMO

Accurate diagnosis of systemic amyloidosis is necessary both for assessing the prognosis and for delineating the appropriate treatment. It is based on histologic evidence of amyloid deposits and characterization of the amyloidogenic protein. We prospectively evaluated the diagnostic performance of immunoelectron microscopy (IEM) of abdominal fat aspirates from 745 consecutive patients with suspected systemic amyloidoses. All cases were extensively investigated with clinical and laboratory data, with a follow-up of at least 18 months. The 423 (56.8%) cases with confirmed systemic forms were used to estimate the diagnostic performance of IEM. Compared with Congo-red-based light microscopy, IEM was equally sensitive (75% to 80%) but significantly more specific (100% vs 80%; P < .001). In amyloid light-chain (AL) amyloidosis, κ cases were more difficult to diagnose (sensitivity 71%), whereas the analysis of abdominal aspirate was informative in only 40% of patients with transthyretin amyloidosis. We found a high prevalence (20%) of a monoclonal component in patients with non-AL amyloidosis, highlighting the risk of misdiagnosis and the need for unequivocal amyloid typing. Notably, IEM identified correctly the specific form of amyloidosis in >99% of the cases. IEM of abdominal fat aspirates is an effective tool in the routine diagnosis of systemic amyloidoses.


Assuntos
Gordura Abdominal/química , Amiloide/análise , Amiloidose/diagnóstico , Amiloidose/metabolismo , Microscopia Imunoeletrônica/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Amiloidose/classificação , Biópsia por Agulha Fina , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Adulto Jovem
20.
Oncotarget ; 6(3): 1874-83, 2015 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-25593199

RESUMO

We have examined serum microRNA expression in multiple myeloma (MM) patients at diagnosis and at complete response (CR) after autologous stem-cell transplantation (ASCT), in patients with stable monoclonal gammopathy of undetermined significance, and in healthy controls. MicroRNAs were first profiled using TaqMan Human MicroRNA Arrays. Differentially expressed microRNAs were then validated by individual TaqMan MicroRNA assays and correlated with CR and progression-free survival (PFS) after ASCT. Supervised analysis identified a differentially expressed 14-microRNA signature. The differential expression of miR-16 (P = 0.028), miR-17 (P = 0.016), miR-19b (P = 0.009), miR-20a (P = 0.017) and miR-660 (P = 0.048) at diagnosis and CR was then confirmed by individual assays. In addition, high levels of miR-25 were related to the presence of oligoclonal bands (P = 0.002). Longer PFS after ASCT was observed in patients with high levels of miR-19b (6 vs. 1.8 years; P < 0.001) or miR-331 (8.6 vs. 2.9 years; P = 0.001). Low expression of both miR-19b and miR-331 in combination was a marker of shorter PFS (HR 5.3; P = 0.033). We have identified a serum microRNA signature with potential as a diagnostic and prognostic tool in MM.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , MicroRNAs/sangue , Mieloma Múltiplo/genética , Mieloma Múltiplo/terapia , Adulto , Idoso , Progressão da Doença , Feminino , Humanos , Masculino , Análise em Microsséries , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Prognóstico , Transplante Autólogo
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